Mixture of HMOS and b. iuvenis

Abstract

The present invention provides a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in promoting bone growth and / or bone development in a subject, optionally by promoting the production of one or more beneficial metabolites selected from selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT).

Description

[0001] MIXTURE OF HMOS AND B. IUVENIS

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture consisting of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT). The present invention also relates to uses thereof, for example in promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject.

[0004] BACKGROUND TO THE INVENTION

[0005] Human milk oligosaccharides (HMOs) have become the subject of much interest in recent years due to their roles in numerous biological processes occurring in the human organism. Mammalian milk contains at least 130 of these complex oligosaccharides (Urashima et al, Milk Oligosaccharides, Nova Biomedical Books, New York, 2011, ISBN: 978-1-61122-831-1). Infancy, especially the first weeks, 3 months, 6 months or 12 months of life is a critical period for the establishment of a balanced gut microbiota. It is known that the modulation of the gut microbiota during infancy and early childhood can prospectively have a significant influence in the future health status of the body. For example, the gut microbiome can have an influence on the development of a strong immune system later in life, as well as normal growth, and even on the development of obesity later in life.

[0006] Bifidobacterium longum subsp. iuvenis is a bacterium adapted for the weaning period, showcasing both the capacity to consume both prebiotic glycans present in breastmilk, known as human milk oligosaccharides (HMOs), and fibers that are administered to infants upon weaning. Reduced abundance of Bifidobacterium species in infants and young children has been correlated to chronic diseases, including asthma and obesity, as well as to lower vaccine response. Researchers have postulated that loss of Bifidobacterium species in the infant gut in populations of developed countries is linked to increased incidence of allergic and autoimmune diseases. Due to the loss of Bifidobacterium species in the infant gut and low breast-feeding rates, there is a need to provide infants with both HMOs and HMO-utilizing bacteria such as B. longum subsp. iuvenis to support a healthy microbiome for long-term health. Thus, there is a need for compositions to improve the health or prevent and / or treat disease in juvenile mammals, infants, young children and children.

[0007] SUMMARY OF THE INVENTION

[0008] The present inventors have surprisingly found that the combination of Bifidobacterium longum subsp. iuvenis, lacto-N-fucopentaose I (LNFP-I) and a HMO mixture can synergistically increase production of one or more beneficial metabolites, such as amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, in the gastrointestinal tract of a subject.

[0009] Furthermore, by adding a structurally complex HMO, like LNFP-I, to HMO blends which typically consisting of HMOs built up from 4 monosaccharides maximally, the present inventors have significantly increased the HMO blend’s complexity. This helps to further close the gap between human breast milk (the gold standard in the field of infant nutrition) and infant formula, as well as opening novel avenues with respect to which metabolites can be produced or produced in higher abundance by the combination of this more complex HMO blend with probiotics.

[0010] The present inventors have demonstrated the value of adding the more complex HMO structures LNFP-I to exisiting HMO blends, which resulted in the production of novel beneficial metabolites, such as amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, and nitrogenous organic compounds. These metabolites offer a diverse array of health benefits, ranging from anti-bacterial properties and boosting the immune system to supporting gastro-intestinal health and energy metabolism. Additionally, some metabolites such as neurotransmitters, have been associated with the gut-brain axis and shown potential for modulation and neuroprotection.

[0011] Therefore, the properties of the combination of the probiotic candidate Bifidobacterium longum subsp. iuvenis, with the prebiotic HMO LNFP-I and a blend of other HMOs (including 2'-FL, DFL, LNT, 6SL, and 3SL, and optionally 3-FL and / or LNnT) exhibits a multipronged effect by synergistically promoting the production of beneficial metabolites. These findings support the use of this combination in improving the health or preventing and / or treating disease in a young subject, such as juvenile mammals, infants, young children and children.

[0012] Accordingly, in a first aspect the invention provides a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in therapy, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N- tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT), preferably

[0013] In some embodiments, the combination is for use in therapy by promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject.

[0014] In a further aspect, the invention provides a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject (for example, an infant or young child), wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT), wherein the subject (for example, the infant or young child) was born by C-section and / or preterm, and / or small for gestational age (SGA) and / or with a low, very low, or extremely low weight at birth (LWB, VLBW, or ELBW) and / or experienced intra-uterine growth retardation (IUGR), and / or was hospitalized the first days following birth and / or took antibiotic the first days following birth and / or was sick at birth, and / or has impaired microbiota and / or dysbiosis of microbiota.

[0015] In a further aspect, the invention provides the use of a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture to promote the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT).

[0016] In some embodiments, the combination is provided in the form of a nutritional composition, preferably wherein the nutritional composition is selected from an infant formula, a starter infant formula, a follow-on or follow-up formula, a baby food, an infant cereal composition, a growing-up-milk, a fortifier such as a human milk fortifier, a supplement such as a pediatric supplement, a pet food, or a pet food supplement. Accordingly, in a further aspect the invention provides a nutritional composition comprising Bifidobacterium longum subsp. iuvenis and a HMO mixture, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT), preferably wherein the nutritional composition is selected from an infant formula, a starter infant formula, a follow-on or followup formula, a baby food, an infant cereal composition, a growing-up-milk, a fortifier such as a human milk fortifier, a supplement such as a pediatric supplement, a pet food, or a pet food supplement.

[0017] In a further aspect, the invention provides the nutritional composition according to the invention for use in therapy.

[0018] In some embodiments, the composition is for use in therapy by promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, wherein the therapy is promoting bone growth and / or bone development and / or increasing bone strength in a subject, optionally wherein the combination promotes the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0019] In some embodiments, the therapy is promoting bone growth and / or bone development and / or decreased bone strength in a subject, wherein the combination promotes the production of vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0020] In some embodiments, the therapy is promoting bone growth and / or bone development and / or decreased bone strength in a subject, wherein the combination promotes the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0021] In some embodiments, the therapy is promoting bone growth and / or bone development and / or decreased bone strength in a subject, wherein the combination promotes the production of SCFA, in the gastrointestinal tract of the subject.

[0022] In some embodiments, the therapy is promoting bone growth and / or bone development and / or decreased bone strength in a subject, wherein the combination promotes the production of acetate, in the gastrointestinal tract of the subject. In some preferred embodiments, the therapy is bone development, such as bone growth and / or bone strength and / or bone quality.

[0023] In a further aspect, the invention provides the nutritional composition according to the invention for non-therapeutical use.

[0024] In some embodiments, the composition is for non-therapeutical use by promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, wherein the use is promoting bone growth and / or bone development and / or decreased bone strength in a subject, optionally wherein the combination promotes the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0025] In some preferred embodiments, the non-therapeutical use is promoting bone development, such as bone growth and / or bone strength and / or bone quality and / or bone formation.

[0026] In some embodiments, the Bifidobacterium longum subsp. iuvenis'.

[0027] a) is capable of metabolizing one or more of the HMO(s), preferably all of the HMOs; b) preferentially utilizes 3-FL over 2’-FL; and / or

[0028] c) is not resistant to any one of tetracycline, erythromycin, clindamycin and ampicillin, preferably wherein the Bifidobacterium longum subsp. iuvenis is not resistant to any of tetracycline, erythromycin, clindamycin, ampicillin, gentamycin, streptomycin, chloramphenicol and vancomycin.

[0029] In some embodiments, the Bifidobacterium longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98% with at least one Bifidobacterium longum strain selected in the group consisting of CNCM I-5942, CNCM 1-5683, CNCM 1-5684, CNCM 1-5685, CNCM 1-5686, CNCM 1-5687, CMCC-P0001 (ATCC BAA-2753), and any combination thereof, preferably wherein the Bifidobacterium longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98%, preferably at least 99%, with the Bifidobacterium longum subsp. iuvenis strain deposited with the CNCM under deposit number CNCM I-5942.

[0030] In some embodiments, the combination or composition comprises from 103to 1012cfu of Bifidobacterium longum subsp. iuvenis, preferably from 107to 1012cfu of Bifidobacterium longum subsp. iuvenis, more preferably from 108to 1010cfu of Bifidobacterium longum subsp. iuvenis per g of combination or composition on a dry weight basis. In some embodiments, the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), and 3-fucosyl lactose (3FL).

[0031] In some embodiments, the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), and lacto-N-neotetraose (LNnT).

[0032] In some embodiments, the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), 3-fucosyl lactose (3FL), and lacto-N-neotetraose (LNnT).

[0033] In a further aspect, the invention provides the use of the nutritional composition according to the invention to promote the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject.

[0034] In a further aspect, the invention provides the nutritional composition according to the invention for use in promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject (for example, an infant or young child), wherein the subject (for example, the infant or young child) was born by C-section and / or preterm, and / or small for gestational age (SGA) and / or with a low, very low, or extremely low weight at birth (LWB, VLBW, or ELBW) and / or experienced intra-uterine growth retardation (IUGR), and / or was hospitalized the first days following birth and / or took antibiotic the first days following birth and / or was sick at birth, has impaired microbiota and / or dysbiosis of microbiota, and / or suffered from and / or is suffering from stunted growth and / or faltering growth.

[0035] In a further aspect, the invention provides a method of promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, the method comprising administering to the subject a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT). The combination or composition may be administered in any suitable manner. Suitably, the combination is administered separately, simultaneously or sequentially. In some embodiments, the combination is administered simultaneously.

[0036] The combination or composition may comprise any suitable Bifidobacterium longum subsp. iuvenis in any suitable amounts.

[0037] The subject may be at risk and / or in need thereof. In some embodiments, the subject (for example, an infant or young child) was born by C-section and / or preterm, and / or small for gestational age (SGA) and / or with a low, very low, or extremely low weight at birth (LWB, VLBW, or ELBW) and / or experienced intra-uterine growth retardation (IUGR), and / or was hospitalized the first days following birth and / or took antibiotic the first days following birth and / or was sick at birth, has impaired microbiota and / or dysbiosis of microbiota, and / or suffered from and / or is suffering from stunted growth and / or faltering growth.

[0038] BRIEF DESCRIPTION OF THE FIGURES

[0039] Figure 1: Acetate, butyrate, propionate, and total short chain fatty acid concentrations for synbiotic compositions.

[0040] Figure 2: Acetate increase over 48 h of incubation in an ex vivo model modeling the infant colon. Bioreactors were inoculated with fecal material of 3-month-old infants to serve as background microbiota. Additionally, B. infantis LMG11588 and / or B. iuvenis CNCM I-5942 were supplemented. As a substrate, HMO blend I and II or the same blends with additionally added LNFP-I were used, with or without probiotics. Solid lines represent the increase over time surrounded by a translucent ribbon representing the 95% compatibility interval. DETAILED DESCRIPTION OF THE INVENTION

[0041] Definitions

[0042] As used herein, the following terms have the following meanings.

[0043] The term "subject" refers to a juvenile mammal, an infant, a young child or a child.

[0044] The term "infant" means a child under the age of 12 months.

[0045] The expression "young child" means a child aged between one and three years, also called toddler.

[0046] The term “child” means a child aged between three and twelve years. Preferably, the term “child” means a child aged between three and six years. A "preterm" or "premature" subject means an infant or young child who was not born at term. Generally it refers to an infant or young child born prior 36 weeks of gestation.

[0047] By the expression "small for gestational age" or " SGA" it is referred to an infant or young child who is smaller in size than normal for their gestational age at birth, most commonly defined as a weight below the 10th percentile for the gestational age. In some embodiments, SGA may be associated with intrauterine growth restriction (IUGR), which refers to a condition in which a foetus is unable to achieve its potential size.

[0048] By the expression “low birth weight”, it should be understood as any body weight under 2500g at birth.

[0049] The expression "nutritional composition" means a composition which nourishes a subject. This nutritional composition is usually to be taken orally or intravenously. It may include a lipid or fat source, a carbohydrate source and / or a protein source. In a particular embodiment the nutritional composition is a ready-to-drink composition such as a ready-to-drink formula. In a particular embodiment, the nutritional composition of the present invention is a "synthetic nutritional composition". The expression "synthetic nutritional composition" means a mixture obtained by chemical and / or biological means, which can be chemically identical to the mixture naturally occurring in mammalian milks (i.e. the synthetic nutritional composition is not breast milk).

[0050] The expression "infant formula" as used herein refers to a foodstuff intended for particular nutritional use by infants during the first months of life and satisfying by itself the nutritional requirements of this category of person (Article 2(c) of the European Commission Directive 91 / 321 / EEC 2006 / 141 / EC of 22 December 2006 on infant formulae and follow-on formulae). It also refers to a nutritional composition intended for infants and as defined in Codex Alimentarius (Codex STAN 72-1981) and Infant Specialities (incl. Food for Special Medical Purpose).

[0051] The expression "infant formula" encompasses both "starter infant formula" and "follow-up formula" or "follow-on formula".

[0052] A "follow-up formula" or "follow-on formula" is given from the 6th month onwards and includes “growing-up milk”. It constitutes the principal liquid element in the progressively diversified diet of this category of person.

[0053] The expression “growing-up milk” (or “GUM”) refers to a milk-based drink generally with added vitamins and minerals, that is intended for young children or children. The expression "baby food" means a foodstuff intended for particular nutritional use by infants or young children during the first years of life.

[0054] The expression "infant cereal composition" means a foodstuff intended for particular nutritional use by infants or young children during the first years of life.

[0055] The term "fortifier" refers to liquid or solid nutritional compositions suitable for mixing with breast milk or infant formula.

[0056] The expression “weaning period” means the period during which the mother's milk is substituted by other food in the diet of an infant or young child.

[0057] The "mother's milk" should be understood as the breast milk or the colostrum of the mother. An “oligosaccharide” is a saccharide polymer containing a small number (typically three to ten) of simple sugars (monosaccharides).

[0058] The term " HMO" or " HMOs" refers to human milk oligosaccharide(s). These carbohydrates are resistant to enzymatic hydrolysis by digestive enzymes (e.g. pancreatic and / or brush border), indicating that they may display functions not directly related to their caloric value. It has especially been illustrated that they play a vital role in the early development of infants and young children, such as the maturation of the immune system. Many different kinds of HMOs are found in the human milk. Each individual oligosaccharide is based on a combination of glucose, galactose, sialic acid (N- acetylneuraminic acid), fucose and / or N-acetylglucosamine with many and varied linkages between them, thus accounting for the enormous number of different oligosaccharides in human milk - over 130 such structures have been identified so far. Almost all of them have a lactose moiety at their reducing end while sialic acid and / or fucose (when present) occupy terminal positions at the non-reducing ends. The HMOs can be acidic (e.g. charged sialic acid containing oligosaccharide) or neutral (e.g. fucosylated oligosaccharide). Some examples of HMOs are the fucosylated oligosaccharides, the N-acetylated oligosaccharides and / or the sialylated oligosaccharides.

[0059] A "fucosylated oligosaccharide" is an oligosaccharide having a fucose residue. It has a neutral nature. Some examples are LNFP-I (lacto-N-fucopentaose I), 2’-FL (2' fucosyllactose), 3-FL (3-fucosyllactose).

[0060] The expressions “fucosylated oligosaccharides comprising an alpha-1, 2-fucosyl-epitope” and “2-fucosylated oligosaccharides” encompass fucosylated oligosaccharides with a certain homology of form since they contain an alpha-1, 2'-fucosyl-epitope, therefore a certain homology of function can be expected. The expression “N-acetylated oligosaccharide(s)” encompasses both “N-acetyl-lactosamine” and “oligosaccharide(s) containing N-acetyl-lactosamine”. They are neutral oligosaccharides having an N-acetyl-lactosamine residue. Suitable examples are LNT (lacto-N-tetraose), para-lacto-N-neohexaose (para-LNnH), LNnT (lacto-N-neotetraose) and any combinations thereof. Other examples are lacto-N-hexaose, lacto-N-neohexaose, para- lacto-N-hexaose, para-lacto-N-neohexaose, lacto-N-octaose, lacto-N- neooctaose, iso- lacto-N-octaose, para- lacto-N-octaose and lacto-N-decaose.

[0061] A "sialylated oligosaccharide" is a charged sialic acid containing oligosaccharide, i.e. an oligosaccharide having a sialic acid residue. It has an acidic nature. Some examples are 3’-SL (3’-sialyllactose) and 6’-SL (6’-sialyllactose). The expressions "sialylated oligosaccharide" and "sialyllactose (SL)" can be used interchangeably. The trisaccharide sialyllactose consists of lactose at the reducing terminus and one sialic acid residue at the non-reducing end via an alpha-2,3 binding or alpha-2,6 binding, resulting in 3'-SL and 6'-SL, respectively.

[0062] A "precursor of HMO" is a key compound that intervenes in the manufacture of HMO, such as sialic acid and / or fucose.

[0063] The term “GOS” as used herein means “Galacto-oligosaccharide". Galacto-oligosaccharides (GOS) as used herein typically consist of β-linked galactose moieties with galactose or glucose at the reducing end. Such GOS contains β-(1→2), β-(1→3), β-(1→4), or β-(1→6) linked galactose moieties and may have a degree of polymerization (DP) of 3-8 galactose units. The term GOS is therefore preferably referred to as oligosaccharide(s) comprising at least three galactose units, more preferably as oligosaccharide(s) comprising at least four galactose units, preferably having a degree of polymerization (DP) of 3-8 galactose units.

[0064] The nutritional composition of the present invention can be in solid form (e.g. powder) or in liquid form. The amount of the various ingredients (e.g. the oligosaccharides) can be expressed in g / 100g of composition on a dry weight basis when it is in a solid form, e.g. a powder, or as a concentration in g / L of the composition when it refers to a liquid form (this latter also encompasses liquid composition that may be obtained from a powder after reconstitution in a liquid such as milk, water, e.g. a reconstituted infant formula or a follow-on / follow-up formula or a growing-up milk or an infant cereal product or any other formulation designed for infant nutrition).

[0065] The expressions “infants / young children fed exclusively with human breast milk”, “infants or young children exclusively breast fed”, “exclusive breast fed infants or young children’and “breast-fed infants / young children” can be used interchangeably. They refer to infants or young children fed with a great majority (i.e. at least 90%, or at least 95%, or at least 99%) or all (100%) of nutrients and / or energy originating from human breast milk.

[0066] The expression “conventional nutritional composition” refers to standard synthetic nutritional compositions such as infant formula, follow-up milks or growing-up milks already found in the market.

[0067] The terms “microbial”, “microflora” and “microbiota” can be used interchangeably.

[0068] The expressions “microbiota in the gut”, “microbiota of the gut”, “gut microbiota” and “intestinal microbiota” can be used interchangeably.

[0069] By the expressions “preventing” or “prevention”, it is meant avoiding that a physical state, a condition or their consequences occurs and / or decreasing its incidence (i.e. reduction of the frequency). Prevention also encompasses delay or prevention of the onset of the symptoms of the disease, disorder or condition. Prevention may be absolute (such that no disease occurs) or may be effective only in some individuals or for a limited amount of time.

[0070] By the expressions “treating” or “treatment”, it is meant a decrease of the duration and / or of the severity of a physical state, a condition or their consequences (e.g. a decrease or elimination of symptoms of the condition). Treatment also encompasses to reduce, alleviate or eliminate one or more symptoms associated with the disease, disorder or condition which is being treated and / or to slow down, reduce or block the progression of the disease, disorder or condition which is being treated.

[0071] The improvement of health, prevention and / or the treatment of a physical state, a condition or their consequences can occur during the treatment (i.e. during the administration of the composition of the present invention, either immediately after the start of the administration or some time after, e.g. some days or weeks after the start). But it can also encompass the improvement of health, prevention and / or the treatment later in life. The term “later in life” encompasses the effect after the termination of the intervention or treatment. The effect “later in life” can be from 1 week to several months, or even years, for example from 2 to 4 weeks, from 2 to 6 weeks, from 2 to 8 weeks, from 1 to 6 months or from 2 to 12 months. Suitably, the effect “later in life” can be from 12 months to 12 years, such as from 2 years to 10 years, or from 4 years to 5 years, after the termination of the intervention or treatment. Suitably, the effect “later in life” lasts until the subject is at least 5 years of age, such as at least 10 years of age.

[0072] The term “prebiotic” means non-digestible carbohydrates that beneficially affect the host by selectively stimulating the growth and / or the activity of healthy bacteria such as bifidobacteria in the colon of humans (Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995;125:1401-12).

[0073] The term “probiotic” means microbial cell preparations or components of microbial cells with a beneficial effect on the health or well-being of the host. (Salminen S, Ouwehand A. Benno Y. etal. “Probiotics: how should they be defined” Trends Food Sci. Technol. 1999:10 107-10). The microbial cells are generally bacteria or yeasts.

[0074] The term “synbiotic” may refer to a component that contains both probiotics and prebiotics, or a live microbe and a substrate that is selectively utilized by the co-administered live microbe (see e.g. Swanson, K. S., et al., 2020. Nature Reviews Gastroenterology & Hepatology, 17(11), pp.687-701).

[0075] The term “cfu” should be understood as colony-forming unit.

[0076] All percentages are by weight unless otherwise stated.

[0077] All weights expressed in g per 100g of composition are dry weight unless otherwise stated. The term “SCFA” means short chain fatty acid(s). The expression “increasing SCFA production” means that the amount of systemic and / or colonic SCFA, is higher in an individual fed with the nutritional composition according to the present invention in comparison with a standard. The SCFA production may be measured by techniques known by the skilled person such as by Gas-Liquid Chromatography.

[0078] In the present context, the term “gastrointestinal tract” includes the mouth, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus. The term “intestine” includes the small intestine, the large intestine and rectum.

[0079] In addition, in the context of the invention, the terms "comprising" or "comprises" do not exclude other possible elements. The composition of the present invention, including the many embodiments described herein, can comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise depending on the needs. Any reference to prior art documents in this specification is not to be considered an admission that such prior art is widely known or forms part of the common general knowledge in the field. The invention will now be described in further details. It is noted that the various aspects, features, examples and embodiments described in the present application may be compatible and / or combined together any combination thereof. Composition and combination

[0080] In a first aspect, the invention provides a composition comprising or consisting of Bifidobacterium longum subsp. iuvenis and a HMO mixture consisting of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT).

[0081] In a further aspect, the invention provides a composition comprising or consisting of Bifidobacterium longum subsp. iuvenis, lacto-N-fucopentaose I (LNFP-I), and a HMO mixture consisting of 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT).

[0082] In a further aspect, the invention provides a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture consisting of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT). In a further aspect, the invention provides a combination of Bifidobacterium longum subsp. iuvenis, lacto-N-fucopentaose I (LNFP-I), and a HMO mixture consisting of 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT). The combination may be administered separately, simultaneously or sequentially. In preferred embodiments, the combination is administered simultaneously. In some embodiments, the combination is administered in the form of a composition, for example any composition described herein.

[0083] Bifidobacterium longum subsp. iuvenis

[0084] Bifidobacterium longum subsp microorganisms of a clade that is present in the gut microbiome of the transitional feeding period of mammals, particularly humans, have previously been identified. B. longum microorganisms belonging to this clade are referred to herein as B. longum subsp. iuvenis and are also known in the art as Bifidobacterium longum transitional (8. longum transitional) microorganisms. B. longum subsp. iuvenis NCC 5000, NCC 5001, NCC 5002, NCC 5003 and NCC 5004 were deposited with the Collection nationale de cultures de micro-organisms (CNCM), Institute Pasteur (INSTITUT PASTEUR, 25 RUE DU DOCTEUR ROUX, F-75724 PARIS CEDEX 15, FRANCE) by SOCIETE DES PRODUITS NESTLE S. A according to Budapest Treaty on 11th of May 2021 receiving the deposit numbers CNCM I- 5683, CNCM 1-5684, CNCM 1-5685, CNCM 1-5686 and CNCM 1-5687, respectively. In US provisional patent application 63 / 216127, it was shown that the B. longum subsp. iuvenis microorganisms are greater in relative abundance during the transitional feeding period (e.g. weaning period) than either B. longum subsp. infantis (B. infantis) or B. longum subsp longum. Indeed, the relative abundance of B. longum subsp. infantis decreases at the beginning of the transitional feeding period until the end of the transitional feeding period while B. longum subsp. longum begins to increase in abundance. Vatanen et al. demonstrated that this distinct Bifidobacterium longum clade expanded with introduction of solid foods and harbored enzymes for utilizing both breast milk and solid food substrates (Vatanen et al.; 2022, Cell 185, 1–18; published online 1 November 2022; https: / / doi.org / 10.1016 / j.cell.2022.10.011).

[0085] Suitably, the B. longum subsp. iuvenis may be as described in WO2023281099 A1 or WO2023161444 A1. Suitably, the B. longum subsp. iuvenis for use according to the present invention may be a B. longum subsp. iuvenis strain disclosed in WO2023281099 A1 or WO2023161444 A1.

[0086] In some embodiments, the B. longum subsp. iuvenis preferentially utilizes 3- fucosyllactose (3-FL) over 2’ -fucosyllactose (2’-FL). Suitably, the B. longum subsp. iuvenis may preferentially utilize 3-FL over 2’-FL in a ratio between 0.1:5, preferably in a ratio between 0.1:4, more preferably in a ratio between 0.2:2.

[0087] In some embodiments, the B. longum subsp. iuvenis used in the present invention utilizes 3-FL more efficiently than 2’-FL, as demonstrated by a better growth.

[0088] In some embodiments, a B. longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 96% with at least one B. longum strain selected in the group consisting of CNCM I- 5683, CNCM I-5684, CNCM I-5685, CNCM I-5686, CNCM I-5687, and CMCC-P0001 (ATCC BAA-2753), and any combination thereof. In some embodiments, a B. longum subsp. iuvenis has an ANI of about 96%, 96.1%, 96.2%, 96.3%, 96.4%, 96.5%, 96.6%, 96.7%, 96.8%, 96.9%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.6 %, 98.7 %, 98.8 %, 98.9 %, 99 %, 99.1 %, 99.2 %, 99.3 %, 99.4 %, 99.5 %, 99.6 %, 99.7 %, 99.8 %, 99.9 %, or 100 % with at least one Bifidobacterium longum strain selected in the group consisting of CNCM I-5683, CNCM I- 5684, CNCM I-5685, CNCM I-5686, CNCM I-5687 and CMCC-P0001 (ATCC BAA-2753), and any combination thereof. In some embodiments, a B. longum subsp. iuvenis has an ANI of at least 96%, of at least 96.1%, of at least 96.2%, of at least 96.3%, of at least 96.4%, of at least 96.5%, of at least 96.6%, of at least 96.7%, of at least 96.8%, of at least 96.9%, of at least 97%, of at least 97.1%, of at least 97.2%, of at least 97.3%, of at least 97.4%, of at least 97.5%, of at least 97.6%, of at least 97.7%, of at least 97.8%, of at least 97.9%, of at least 98%, of at least 98.1%, of at least 98.2%, of at least 98.3%, of at least 98.4%, of at least 98.5%, of at least 98.6%, of at least 98.6 %, of at least 98.7 %, of at least 98.8 %, of at least 98.9 %, of at least 99 %, of at least 99.1 %, of at least 99.2 %, of at least 99.3 %, of at least 99.4 %, of at least 99.5 %, of at least 99.6 %, of at least 99.7 %, of at least 99.8 %, of at least 99.9 % with at least one Bifidobacterium longum strain selected in the group consisting of CNCM I-5683, CNCM I-5684, CNCM I-5685, CNCM I-5686, CNCM I-5687 and CMCC-P0001 (ATCC BAA-2753), and any combination thereof.

[0089] In some embodiments, a B. longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98% with at least one B. longum strain selected in the group consisting of CNCM I- 5683, CNCM I-5684, CNCM I-5685, CNCM I-5686 and CNCM I-5687, and any combination thereof. In some embodiments, a B. longum subsp. iuvenis has an ANI of about 98% to 100% with at least one B. longum strain selected in the group consisting of CNCM I-5683, CNCM I- 5684, CNCM I-5685, CNCM I-5686 and CNCM I-5687, and any combination thereof. In some embodiments, a B. longum subsp. iuvenis has an ANI of at least 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.6 %, 98.7 %, 98.8 %, 98.9 %, 99 %, 99.1 %, 99.2 %, 99.3 %, 99.4 %, 99.5 %, 99.6 %, 99.7 %, 99.8 %, 99.9 %, or 100 % with at least one B. longum strain selected in the group consisting of CNCM I-5683, CNCM I-5684, CNCM I-5685, CNCM I-5686 and CNCM I-5687, and any combination thereof. In some embodiments, a B. longum subsp. iuvenis has an ANI of at least 98.6%, of at least 98.6 %, of at least 98.7 %, of at least 98.8 %, of at least 98.9 %, of at least 99 %, of at least 99.1 %, of at least 99.2 %, of at least 99.3 %, of at least 99.4 %, of at least 99.5 %, of at least 99.6 %, of at least 99.7 %, of at least 99.8 %, of at least 99.9 % or of at least 100% with at least one B. longum strain selected in the group consisting of CNCM I-5683, CNCM I-5684, CNCM I-5685, CNCM I-5686 and CNCM I-5687, and any combination thereof.

[0090] B. longum subsp. iuvenis strain NCC 5025 was deposited with the Collection Nationale de Cultures de Micro-organisms (CNCM), Institute Pasteur by SOCIETE DES PRODUITS NESTLE S. A according to Budapest Treaty on the 29thof March 2023 receiving the deposit number CNCM I-5942.

[0091] The B. longum subsp. iuvenis for use according to the invention may have an Average Nucleotide Identity (ANI) of at least 98% with CNCM I-5942 and / or may have at least one identifying characteristic of the B. longum subsp. iuvenis strain deposited under deposit number CNCM I-5942.

[0092] Suitably, the B. longum subsp. iuvenis for use according to the invention has an Average Nucleotide Identity (ANI) of at least 98% with CNCM I-5942. Suitably, the B. longum subsp. iuvenis for use according to the invention has at least one identifying characteristic of the B. longum subsp. iuvenis strain deposited under deposit number CNCM I-5942. Suitably, the B. longum subsp. iuvenis for use according to the invention has an Average Nucleotide Identity (ANI) of at least 98% with CNCM I-5942 and has at least one identifying characteristic of the B. longum subsp. iuvenis strain deposited under deposit number CNCM I-5942.

[0093] Suitably, the B. longum subsp. iuvenis may be B. longum subsp. iuvenis NCC 5025. Suitably, the B. longum subsp. iuvenis may be a B. longum subsp. iuvenis strain deposited with CNCM under deposit number CNCM I-5942 or a B. longum subsp. iuvenis strain having at least one identifying characteristic of the B. longum subsp. iuvenis strain deposited under deposit number CNCM I-5942.

[0094] Suitably, an identifying characteristic of the present B. longum subsp. iuvenis strain may refer to one or more of the phenotypic or genotypic characteristics described herein.

[0095] Suitably, the B. longum subsp. iuvenis strain has an Average Nucleotide Identity (ANI) of at least 99% to the B. longum subsp. iuvenis strain deposited with the CNCM under deposit number CNCM I-5942.

[0096] In some embodiments, the B. longum subsp. iuvenis strain has an ANI of at least at least 99.0%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9%, compared to the B. longum strain deposited with the CNCM under deposit number CNCM I-5942.

[0097] Preferably, the B. longum subsp. iuvenis strain has an ANI of at least 99.9% compared to the B. longum strain deposited with the CNCM under deposit number CNCM I-5942.

[0098] Suitably, the B. longum subsp. iuvenis strain has an ANI of at least 98.1%, at least 98.2%, at least 98.3%, at least 98.4%, of at least 98.5%, of at least 98.6%, of at least 98.6 %, of at least 98.7 %, of at least 98.8 %, of at least 98.9 %, of at least 99 %, of at least 99.1 %, of at least 99.2 %, of at least 99.3 %, of at least 99.4 %, of at least 99.5 %, of at least 99.6 %, of at least 99.7 %, of at least 99.8 %, or of at least 99.9 % compared to the B. longum strain deposited with the CNCM under deposit number CNCM I-5942 and has at least one identifying characteristic of the B. longum subsp. iuvenis strain deposited under deposit number CNCM I-5942 - as described herein.

[0099] Suitably, the B. longum subsp. iuvenis strain has an ANI of at least 98.4%, of at least 98.5%, of at least 98.6%, of at least 98.6 %, of at least 98.7 %, of at least 98.8 %, of at least 98.9 %, of at least 99 %, of at least 99.1 %, of at least 99.2 %, of at least 99.3 %, of at least 99.4 %, of at least 99.5 %, of at least 99.6 %, of at least 99.7 %, of at least 99.8 %, or of at least 99.9 % compared to the B. longum strain deposited with the CNCM under deposit number CNCM 1-5942 and has at least one identifying characteristic of the B. longum subsp. iuvenis strain deposited under deposit number CNCM I-5942 - as described herein.

[0100] Methods for sequencing microbial genomes are well known in the art (see e.g. Segerman; Front. Cell. Infect. Microbiol.; 2020; 10; Article 527102 & Donkor; Genes; 2013; 4(4); 556-572). By way of example, metagenomics methods may be used. Suitable metagenomics methods may be performed using shotgun sequencing data, for example. Suitable metagenomics methods are known in the art and include MetaPhlAn 3.0, for example (see Beghini et al.; eLife 2021;10: e65088; https: / / huttenhower.sph.harvard.edu / metaphlan).

[0101] The “Average Nucleotide Identity (ANI)” is a term of art that refers to a distance-based approach to delineate species based on pair-wise comparisons of their genome sequences and is an in silico alternative to the traditional DNA-DNA hybridization (DDH) techniques that have been used for phylogenetic definition of a species (Goris et al., 2007, “DNA-DNA hybridization values and their relationship to whole-genome sequence similarities”, Int. J. Syst. Evol. Microbiol. 57: 81-91). Based on DDH, strains with greater than 70% relatedness would be considered to belong to the same species (see e.g., Wayne et al., 1987, Report of the Ad-Hoc-Committee on Reconciliation of Approaches to Bacterial Systematics. Int J Syst Bacteriol 37: 463-464). ANI is similar to the aforementioned 70% DDH cutoff value and can be used for species delineation. ANI has been evaluated in multiple labs and has become the gold standard for species delineation (see e.g., Kim et al., 2014, “Towards a taxonomic coherence between average nucleotide identity and 16S rRNA gene sequence similarity for species demarcation of prokaryotes”, Int. J. Syst. Evol. Mier. 64: 346-351; Richter et al., 2009, “Shifting the genomic gold standard for the prokaryotic species definition”, P Natl Acad Sci USA 106: 19126-19131; and Chan et al., 2012, “Defining bacterial species in the genomic era: insights from the genus Acinetobacter”, Bmc. Microbiol. 12)).

[0102] The ANI of the shared genes between two strains is known to be a robust means to compare genetic relatedness among strains, and that ANI values of about 95% correspond to the 70% DNA-DNA hybridization standard for defining a species. See, e.g., Konstantinidis and Tiedje, Proc Natl Acad Sci USA, 102(7):2567-72 (2005); and Goris et al., Int Syst Evol Microbiol. 57(Pt 1 ):81 -91 (2007). The ANI between two bacterial genomes is calculated from pair-wise comparisons of all sequences shared between any two strains and can be determined, for example, using any of a number of publicly available ANI tools, including but not limited to OrthoANI with usearch (Yoon et al. Antonie van Leeuwenhoek 110:1281-1286 (2017)); ANI Calculator, JSpecies (Richter and Rossello-Mora, Proc Natl Acad Sci USA 106:19126-19131 (2009)); and JSpeciesWS (Richter et al., Bioinformatics 32:929-931 (2016)). Other methods for determining the ANI of two genomes are known in the art. See, e.g., Konstantinidis, K. T. and Tiedje, J. M., Proc. Natl. Acad. Sci. U. S. A., 102: 2567-2572 (2005); and Varghese et al., Nucleic Acids Research, 43(14):6761-6771 (2015). In a particular embodiment, the ANI between two bacterial genomes can be determined, for example, by averaging the nucleotide identity of orthologous genes identified as bidirectional best hits (BBHs). Protein-coding genes of a first genome (Genome A) and second genome (Genome B) are compared at the nucleotide level using a similarity search tool, for example, NSimScan (Novichkov et al., Bioinformatics 32(15): 2380-2381 (2016)). The results are then filtered to retain only the BBHs that display at least 70% sequence identity over at least 70% of the length of the shorter sequence in each BBH pair. The ANI of Genome A to Genome B is defined as the sum of the percent identity times the alignment length for all BBHs, divided by the sum of the lengths of the BBH genes. These and ANI determination techniques are known in the art.

[0103] Suitably, a B. longum microorganism selected from the group consisting of CNCM I-5942, CNCM I-5683, CNCM I-5684, CNCM I-5685, CNCM I-5686 and CNCM I-5687, represents the reference genome to which a microbial genome is compared.

[0104] Suitably, a B. longum microorganism selected from the group consisting of CNCM I-5942, CNCM I-5683, CNCM I-5684, CNCM I-5685, CNCM I-5686, CNCM I-5687 and CMCC-P0001 (ATCC BAA-2753), represents the reference genome to which a microbial genome is compared.

[0105] Genome sequences for B. longum subsp. iuvenis strains NCC 5000 (CNCM I-5683), NCC 5001 (CNCM I-5684), NCC 5002 (CNCM I-5685), NCC 5003 (CNCM I-5686) and NCC 5004 (CNCM I-5687) are available via Joint Genome Project (JGI) Study number: Gs0156595 (https: / / genome.jgi.doe.gov / portal / ). Analysis project numbers and taxon numbers for each genome are as follows:

[0106] Strain JGI analysis project JGI taxon

[0107] B. longum NCC 5000 Ga0527908 2951181949 B. longum NCC 5001 Ga0529016 2951184202 B. longum NCC 5002 Ga0529017 2951186501 B. longum NCC 5003 Ga0529018 2951188792 B. longum NCC 5004 Ga0529019 2951191018

[0108]

[0109] In some embodiments, the B. longum subsp. iuvenis for use in the present invention is isolated from a human. In some other embodiments, the B. longum subsp. iuvenis is not of the subspecies B. longum subsp. longum or B. longum subsp. infantis.

[0110] Suitably, the B. longum subsp. iuvenis is provided as a probiotic. Suitably, the B. longum subsp. iuvenis is provided in a composition.

[0111] The composition or combination according to the invention may contain from 103to 1012cfu of the B. longum subsp. iuvenis, more preferably from 107to 1012cfu such as from 108to 1010cfu of the B. longum subsp. iuvenis per g of composition or combination on a dry weight basis. Suitably, the B. longum subsp. iuvenis is administered to the subject in an amount of at least about 106cfu / day, at least about 107cfu / day, or at least about 108cfu / day. Suitably, the B. longum subsp. iuvenis is administered to the subject in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less.

[0112] In one embodiment, the B. longum subsp. iuvenis is viable.

[0113] Antibiotic resistance

[0114] Suitably, the B. longum subsp. iuvenis strain does not harbor transferable antibiotic resistance to one or more antibiotics, preferably one or more European Food Standard Agency (EFSA) relevant antibiotics (see European Food Safety Authority. 2012. Guidance on the assessment of bacterial susceptibility to antimicrobials of human and veterinary importance. EFSA J 10:2740).

[0115] Antibiotic resistance refers to the ability of microorganisms to withstand antibiotic treatments. The overuse or misuse of antibiotics has been linked to the emergence and spread of microorganisms which are resistant to them, rendering treatment ineffective and posing a serious risk to public health. In addition, the wide-spread use of antibiotics means that it is increasingly challenging to provide bacterial strains that do not have transferrable resistance to one or more EFSA relevant antibiotics.

[0116] It is known that a single gene may instill antibiotic resistance against a particular antibiotic, and that bacteria can transfer genes through horizontal gene transfer via conjugation, transduction or transformation. Accordingly, it is known that antibiotic resistance may be transferred between bacteria via horizontal gene transfer; including in the gut microbiome. It is therefore advantageous that the present B. longum subsp. iuvenis strain does not harbor transferrable antibiotic resistance to one or more antibiotics as this reduces the risk of the antibiotic resistance being transferred to other components of the microbiome when the present B. longum subsp. iuvenis strain is used as a probiotic. Antibiotics resistance has been well-described and antibiotic resistance may be determined using any suitable assay known in the art. By way of example, phenotypic and / or genetic methods may be used. Phenotypic methods typically involve measuring the growth of a test bacteria in the presence of a suitable concentration of the antibiotic under consideration. In addition, a number of genes mediating antibiotic resistance are known. Accordingly, genetic methods for determining antibiotic resistance comprise determining the presence of one or more antibiotic resistance genes in the genome of the test bacteria (for example by PCR, DNA microarray, whole-genome sequencing and metagenomics, and matrix-assisted laser desorption ionization-time of flight mass spectrometry). Suitably, phenotypic antibiotic testing of may be performed according to the recommendations made by EFSA (EFSA J 16, e05206, doi:10.2903 / j.efsa.2018.5206 (2018)); for example following the official method ISO 10932. An illustrative method for determining antibiotic resistance is detailed in the present Examples. Antibiotic resistance and underlying genes present in Bifidobacterium are known in the art (see e.g. Duranti etal.-, Appl Environ Microbiol. 2017 Feb 1; 83(3): e02894-16.). As such, the skilled person is able to determine whether a test Bifidobacterium is resistant to one or more antibiotics.

[0117] Suitably, the present B. longum subsp. iuvenis strain is not resistant to at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 EFSA relevant antibiotics.

[0118] Suitably, the B. longum subsp. iuvenis strain is not resistant to any one of tetracycline and erythromycin.

[0119] Suitably, the B. longum subsp. iuvenis strain is not resistant to any one of tetracycline, erythromycin, clindamycin and ampicillin.

[0120] Suitably, the B. longum subsp. iuvenis strain is not resistant to any of tetracycline, erythromycin, clindamycin, ampicillin, gentamycin, streptomycin, chloramphenicol and vancomycin.

[0121] Resistance to tetracycline may be afforded by tet(W) or tet(Q) genes which encode ribosomal protection proteins. Suitably, the present B. longum subsp. iuvenis strain may lack a tet(W) gene. Suitably, the present B. longum subsp. iuvenis strain may lack a tet(W) gene encoding a polypeptide shown as SEQ ID NO: 1 or a variant which shares at least 80% sequence identity to SEQ ID NO: 1. Suitably, the variant may share at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity with SEQ ID NO: 1. SEQ ID NO: 1 MKIINIGILAHVDAGKTTLTESLLYASGAISEPGSVEKGTTRTDTMLLERQRGITIQAAVTSFQWHRCKVNIVDT PGHMDFLAEVYRSLAVLDGAILVI SAKDGVQAQTRILFHALRKMNIPTVIFINKIDQAGVDLQSWQSVRDKLSA DIIIKQTVSLSPEIVLEENTDIEAWDAVIENNDKLLEKYIAGEPISREKLVREEQRRVQDASLFPVYYGSAKKGL GIQPLMDAVTGLFQPIGEQGSAALCGSVFKVEYTDCGQRRVYLRLYSGTLRLRDTVALAGREKLKITEMRIPSKG EIVRTDTAYPGEIVILPSDSVRLNDVLGDPTRLPRKRWREDPLPMLRTSIAPKTAAQRERLLDALTQLADTDPLL RCEVDSITHEIILSFLGRVQLEWSALLSEKYKLETWKEPTVIYMERPLKAASHTIHIEVPPNPFWASIGLSVT PLPLGSGVQYKSRVSLGYLNQSFQNAVRDGIRYGLEQGLFGWNVTDCKICFEYGLYYSPVSTPADFRSLAPIVLE QALKESGTQLLEPYLSFTLYAPREYLSRAYHDAPKYCATIETVQVKKDEWFTGEIPARCIQAYRTDLAFYTNGQ SVCLTELKGYQAAVGKPVIQPRRPNSRLDKVRHMFSKIT

[0122] Suitably, the present B. longum subsp. iuvenis strain may lack a tet(Q) gene. Suitably, the present B. longum subsp. iuvenis strain may lack a tet(Q) gene encoding a polypeptide shown as SEQ ID NO: 2 or a variant which shares at least 80% sequence identity to SEQ ID NO: 2. Suitably, the variant may share at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity with SEQ ID NO: 2.

[0123] SEQ ID NO: 2 MRFDNASNWYYCLIQMNIINLGILAHIDAGKTSVTENLLFASGATEKCGRVDNGDTITDSMDIEKRRGITVRAS TTSIIWNGVKCNIIDTPGHMDFIAEVERTFKMLDGAVLILSAKEGIQAQTKLLFNTLQKLQIPTIIFINKIDRAG VNLERLYLDIKTNLSQDVLCMQTWDGSVYPVCSQTYIKEEYKEFVCDHDDNILERYLADSEIPPTDYWNTIIAL VAKAKVYPVLHGSAMFNIGINELMDAITSFILPPASVSDRLSAYLYKIEHDPKGHKRSFLKIIDGSLRLRDWRI NDSEKSIKIKNLKTIYQGREINVDEVGANDIAIVEDMEDFRIGDYLGAEPCLIQGLSHQHPALKSSVRPDKPEER SKVI SALNTLWIEDPSLSFSINSYSDELEISLYGLTQKEIIQTLLEERFSVKVHFDEIKTIYKERPIKKVNKIIQ IEVPPNPYWATIGLTLEPLPLGAGLQIESDISYGYLNHSFQNAVFEGIRMSCQSGLHGWEVTDLKVTFTQAEYYS PVSTPADFRQLTPYVFRLALQQSGVDILEPMLYFELQIPQEASSKAITDLQKMMSEIEDISCNNEWCHIKGKVPL NTSKDYASEVSSYTKGLGIFMVKPCGYQITKDGYSDNIRMNEKDKLLFMFQKSMSLK

[0124] Resistance to erythromycin may be afforded by the erm(49) gene which encodes a rRNA methylase. Suitably, the present B. longum subsp. iuvenis strain may lack a erm(49) gene. Suitably, the present B. longum subsp. iuvenis strain may lack of erm(49) gene encoding a polypeptide shown in SEQ ID NO: 3or a variant which shares at least 80% sequence identity to SEQ ID NO: 3. Suitably, the variant may share at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity with SEQ ID NO: 3.

[0125] SEQ ID NO: 3 MRNIKDTQNFLHSKELVRHLIGICNIKLDDWIEIGPGKGIITNELAHKARKWAIEFDEELYEKLKNKFQSNNK VDIIYGDILNYTPRIPSYCVFSNIPFNITSEILNKFLSDKKNEKMFLIMQYEPFIKYAGNPYGAETLRSMLYKPF FDMDLKYRFDPSDFKPAPQARIVLASFERKQFPDVKKEEEKLYKDFLAYIYTNKGETFFAKIKTLFSSNQIKRVW GQIKIDKTTKISEVPYESILKVFKLFFLYGTDANKQLWNSFNNMNKQNNKLQKNHRNNSKAKSWNSNRKRKPYH RNNV

[0126] Resistance to erythromycin and clindamycin may be afforded by the erm(X) gene which encodes a ribosomal protection protein. Suitably, the present B. longum subsp. iuvenis strain may lack an erm(X) gene. Suitably, the present B. longum subsp. iuvenis strain may lack an erm(X) gene which encodes a protein comprising SEQ ID NO: 4 or a variant which shares at least 80% sequence identity to SEQ ID NO: 4. Suitably, the variant may share at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity with SEQ ID NO: 4. SEQ ID NO: 4 MSAYGHGRHENGQNFLTNHKIINSIIDLVKQTSGPIIEIGPGSGALTHPMAHLGRAITAVEVDAKLAAKLTQETS SAAVEWHDDFLNFRLPATPCVIVGNIPFHLTTAILRKLLHAPAWTDAVLLMQWEVARRRAGVGASTMMTAQWSP WFTFHLGSRVPRTAFRPQPNVDGGILVIRRVGDPKIPIEQRKAFQAMVHTVFTARGRGIGEILRRAGLFSSRSET QSWLRSRGIDPATLPPRLHTNDWIDLFQVTGSSLPHHRPISPSGSSQRPPQQKNRSRRR

[0127] Resistance to streptomycin may be afforded by a mutation within the rpSL gene which encodes a ribosomal S12 protein. More specifically, a mutation at nucleotide position 128, replacing an A residue to a G residue was shown to provide streptomycin resistance (see Kiwaki & Sato; Int J Food Microbiol. 2009 Sep 15;134(3):211-5). Suitably, the present B. longum subsp. iuvenis strain may have an A residue a position 128 of the rpSL gene. Suitably, the present B. longum subsp. iuvenis strain does not comprise a G128A mutation in the rpSL gene. An illustrative rpSL gene sequence comprising an A at position 128 is shown as SEQ ID NO: 5.

[0128] SEQ ID NO: 5 TTGCCTACTATTGAACAGCTCGTCCGTAAGGGACGTCAGGCAAAGCCGAAGAAGTCCAAGACTTTGGCCCTGAAG GGCAGCCCGCTGCGTCGCGGCGTGTGCACCCGTGTCTACACCACCACCCCGAAGAAGCCGAACTCGGCTCTGCGT AAGGTCGCTCGTGTGCGCCTGTCCTCGGGCATCGAAGTCACCGCCTACATTCCGGGCGAGGGCCACAACCTGCAG GAGCACTCCATCGTGCTCGTGCGCGGCGGCCGTGTGAAGGATCTCCCGGGTGTGCGTTACCACATCGTGCGTGGC GCGCTCGATACCCAGGGTGTCAAGGACCGTAAGCAGGGTCGTTCCCTGTATGGAGCAAAGAAGGCGAAGTAA

[0129] Resistance to chloramphenicol may be afforded by the crmX gene which encodes a ribosomal protection protein. Suitably, the present B. longum subsp. iuvenis strain may lack a crmX gene. Suitably, the present B. longum subsp. iuvenis strain may lack a crmX gene encoding a polypeptide comprising SEQ ID NO: 6 ora variant which shares at least 80% sequence identity to SEQ ID NO: 6. Suitably, the variant may share at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity with SEQ ID NO: 6.

[0130] SEQ ID NO: 6 MPFALYMLALAVFVMGTSEFMLAGLLPAIATELDVSVGTAGLLTSAFAVGMWGAPVMAAFARRWPPRLTLIVCL LVFAGSHVIGAMTPVFSLLLITRVLSALANAGFLAVALSTATTLVPANQKGRALSILLSGTTIATWGVPAGALL STALGWRTTFWAIAILCIPAAVGVIRGVTNNVGRSETSATSPRLRVELSQLATPRLILAMALGALNNGGTFAAFT FLAPIVTETAGLAEAWVSVALVMFGIGSFLGVTIAGRLSDQRPGLVLAVGGPLLLTGWIVLAWASHPVALIVLV LVQGFLSFGVGSTLITRVLYAASGAPTMGGSYATAALNIGAAAGPVLGALGLATGLGLLAPVWVASVLTAIALVI MLLT RRALT KTAAEAN

[0131] Carbohydrate-Active Enzymes (CAZymes)

[0132] Suitably, the B. longum subsp. iuvenis encodes a specific profile of Carbohydrate-Active Enzymes (CAZymes).

[0133] Carbohydrate-active enzymes (CAZymes) are responsible for the synthesis and breakdown of glycoconjugates, oligo- and polysaccharides. They typically correspond to 1-5% of the genes in the living organism. Glycoconjugates, oligo- and polysaccharides play essential roles in many biological functions, for example as structure and energy reserve components and in many intra- and intercellular events. The Carbohydrate Active Enzyme (CAZy) classification is a sequence-based family classification system that correlates with the structure and molecular mechanism of CAZymes (www.cazy.org).

[0134] CAZymes include glycoside hydrolyases (GH), glycosyltransferases (GT), polysaccharide lyases (PL), carbohydrate esterases (CE), and carbohydrate-binding module families (CBM).

[0135] Suitably, the CAZyme may be a glycoside hydrolyase (GH). GHs catalyze the hydrolysis of glycosidic bonds between two or more carbohydrates or between a carbohydrate and a noncarbohydrate moiety. In most cases, the hydrolysis of the glycosidic bond is catalyzed by two amino acid residues of the enzyme: a general acid (proton donor) and a nucleophile / base. Depending on the spatial position of these catalytic residues, hydrolysis occurs via overall retention or overall inversion of the anomeric configuration.

[0136] A GH classification system is provided by the CAZy classification. Herein, GHs are divided into families based on molecular function (e.g., GH1, GH2, GH3, GH4, etc.). These families are then further divided into subfamilies based on subgroups found within a family that share a more recent ancestor and, typically more uniform in molecular function (e.g., GH13_1, GH13_2, GH13_3, GH13_4, etc.).

[0137] Suitably, the present B. longum subsp. iuvenis strain encodes a glycosyl hydrolase family 43_17 (GH43_17) enzyme. GH43_17 comprises both a-L-arabinofuranosidase (EC 3.2.1.55) and endo-p-1,4-xylanase (EC 3.2.1.8) activities, with capacity to breakdown complex carbohydrates like arabinan, arabinogalactan, and arabinoxylan. Suitably, the GH43_17 gene comprises SEQ ID NO: 7 or a sequence with at least 60% sequence identity to SEQ ID NO: 7. Suitably, the GH43_17 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 7.

[0138] SEQ ID NO: 7 ATGAAACGAACTGACATCCACCTGCGCGATCCGTTCGTCCTGCCTCACGACGGTGTCTATTACCTGTATGGCACC CGCGCTGATAACGTGTGGGGCGCGATGGATGGTTTTGATTGCTACACCAGCCGCGACCTTGACAATTGGGAGGGT CCGTTCGAGGTGTTCCACAAGCCGGATGAATTCACGGCCGACCGTGCTTACTGGGCGCCCGAATGCTACGAGCGA GACGGTGTATTCCACCTGATTGCCACGCTCGGCGAGCCGGACGGGCGCAAAAGCGTGCACATGCTACGCGCTGAT AGTCCGCTTGATCCGTTCGAATATGTCTGCCGGCTGACCGATCCGAATCAGTCCTGCATTGACGGAACTCTGCAT GGTGAAGGTACCGATATGTGGCTTGTCTACTCGCATTCCTTGGAGGATGTGCCCGCCGGAGACATGGATGCCGTA CGTCTGTCCTCCGACCTGACTCGGACGGTGGGGGAGAGCATGACATTGTTCCAGGCCTCGGATGCGCCGTGGGCG GTGCCGGTGCCGTTCGCGAAAGCGGAATTCGGCATCGACGAGGACGCCTACTTCTCCGATGGTCCCTGCCTGTGC AGGCTTTCCAACGGACGGCTGGCGATGCTGTGGTCGAGCTGGTCGACGGAAGGCGGATATGCAGTCGGCCAGGCC ATCAGCGAATCAGGGTCGATTGCTGGGCCTTGGACGCAATGCCCCGAGCCTCTGCTTAGCCACGGCGGCCACGGC ATGCTGTTCAACGGTCTCGATGGCGTGCTGCGTTACGCGGTCCACTCGCCCAACGACCCCGGCCAGGAACGGCCT ACGTTTTTGTGCGTCGAAGAACAAGACGGGCTGCTGACGATTACGGAATAG Suitably, the GH43_17 gene may encode a protein shown as SEQ ID NO: 8 or a sequence with at least 80% sequence identity to SEQ ID NO: 8. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 8.

[0139] SEQ ID NO: 8 MKRTDIHLRDPFVLPHDGVYYLYGTRADNVWGAMDGFDCYTSRDLDNWEGPFEVFHKPDEFTADRAYWAPECYER DGVFHLIATLGEPDGRKSVHMLRADSPLDPFEYVCRLTDPNQSCIDGTLHGEGTDMWLVYSHSLEDVPAGDMDAV RLSSDLTRTVGESMTLFQASDAPWAVPVPFAKAEFGIDEDAYFSDGPCLCRLSNGRLAMLWSSWSTEGGYAVGQA ISESGSIAGPWTQCPEPLLSHGGHGMLFNGLDGVLRYAVHSPNDPGQERPTFLCVEEQDGLLTITE

[0140] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 43_22 (GH43_22) gene. Suitably, the GH43_22 gene comprises SEQ ID NO: 9 and / or 10, or a sequence with at least 60% sequence identity to SEQ ID NO: 9 or 10. Preferably, the present B. longum subsp. iuvenis strain comprises a GH43_22 gene with at least 60% sequence identity to SEQ ID NO: 9 and a GH43_22 gene with at least 60% sequence identity to SEQ ID NO: 10. Suitably, the GH43_22 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 9 or 10.

[0141] SEQ ID NO: 9 GTGAAGCATTGGAAGAAGATGGCAGCATCGTTGGTTGCAATATCAACGATGATGGCAGTAGTTCCGACGACGTAT GCCATGGAATCGGAAGATTCCCAACCACAGACAACCGATACCGCGACAGTGCAGACTACTAAGGCTGCTGAACCG ACGCTGCTCGCCAGCTGGGACTTCACGGGCAAAAACGGCACCACGAACAGCGCGATTGCCGATTCGACCGGCAAG TACAACCTGACGCTGAAGGACGGCGCCAAGATCGAACAGTACGGTGACCGCAGCACCAACGAGGCGCTCTCACTG CGCGGCGATGGCCAGTACGCCCAGATCGATGACCAGCTGTTCAAGGATGCGGGCGACTCCTTCACTCTGGAGTTC GCGTCCAAGACTCGTCACGACGACAGCGGCAAGTTCTTCTCGTTCATCGTCGGCAAGGACGGCTCGAACGACGCC AACACCACCGATCAGGCCAACGCCAACAAGTACCTGATGTTCTACAACAGCAAGACCGCCATCAAGGGCGTTATC TCAAACAACAACTGGGGTAACGAACAGGGATCCAAGGTCACCGTTTCCGGCAACGACAACAGCTGGGCCGATTAC AAGATTGTCGTGGACGGCACCAACCTTGCCGTGTTCCGCAACAATGCCCTGATTATTTTCAAGGCCAACACCGGC ATCAAGATGAGCGATCTCGGTGCGACCACCGCCTACATCGGCAAGTCGTTCTACTCCGTCGATGAGTACTGGAAT GGTGCAATGGATGATATCAAGGTCTACAGGGGCGCTGACCTGACCATGCCGACCGCCGTTGCGATTTCCGGTACC GGTGTGGTGAACAACAAGCTCACCCTGATTGAGAAGGACTCCACCAAGCTCACCGCCACCGTCACTCCGGACGAC GCCGTGAGCAAGAACGTCACCTGGTCCTCCTCCGATGAGTCCGTGGCCAAGGTCGCCGCAGACGGTACTGTAACC GGCGTCAAGGCTGGTACTGCCACCATCACCGCCACCACTGAGCTGGGTGGTGTGAAGGCCGAACTGCCCGTCACC GTTGAGCCGATGAACGCCCAGAACGCCGCCGCAGCCGACCTCGATGCCGCGATTGCTGCGCTGAAAGTTCCGGCG GCCGAGAATCTGCCGCTAGTCGCCAAGGGCACCAAGAACGGCTCGGCGATTACGTGGAAGTCCTCGGACGAGAAG CTCATTACGTCCACTAACGAGAAGTACGAAAACAAGACCACTGGTGCCGATGACCCGTATCGTGGTGCTGGCATC ATCAATCGTCCGGCCTACGGCGACGGTGATTCCAAGCCGGTTACGCTGACCGCCACCGCTTCCTACAACGGCGGT GAGAAGGTCACCAAGACCATCGAGGTCACTGTCAAGGAGAAGACCCGCATCGCGCCTGACACCGGCTATGCGGCC GTCACTTTTGAGAGCGACAGCAACGGTGGAGAAAAGGCCTGGGTGGCTTCCACTGAGAAGAACGATTTCTTCACG TTTAAGACTCGCAACAATGGCCAGGCGGTACTTACCAATGATGCAGACACGGGTGGCTTGCGTGACATGTTCGTG CTGCGTTCCCACGAAGGCGACAAGTACTACCTGATTGCCACTGATCTCAAGGTCTCGTCAATGGGCTGGAGCCAG AACCAGGTTAACGGTTCTCGGAAAGTTGAGGTCTACGAGTCCACCGATATGATGAACTGGACCCGTACCAACGGC GACGGCAACGGCGGCATCACCATCAACACGCCGAACGCCGGTATGACCTGGGCGCCGGAAGCTTACTGGGATGAT GACCTGAACGCTTACGTGGTGTTCTTCTCTTCCCGCATGTTCACTGATGACACCCGTACCACTCCGGTCAAGAAC GACAAAACCGGCAATAGCTCCTATGCTCAGGTGCGTTACGCCATCACCCGCGACTTCGTGAACTTCACCGAGCCG CAGATGTGGCAGGACACCGGCTACTCGCGCATTGATTCCACCGTGCGTAAGATCGGTGGCTACTACTACCGATTC ACCAAGAATGAGCAGGGCGGTGCCGCTGGCGATTACATCACCACTGGTAAGAGCATCTTCCTTGAGCGTTCCAAG GTGCTGACTGCACCGACCACCGAGGCATCTCCGGGTCAGGACCCGAACACCGGTTGGCAGTGCTCGAGCAGGCGT TGCTGCCGTTCGAAGGACCAGAGACCATCAAGCTCAACAAGGATGACGAACTCAACACGAAGGACGACGACGGCT ACATTCTGCTGTCCGACAACTTCGCCTACCGTGCATTTATGACCACGGGTGCCGAGCTTTCCAAGACCACGTGGG ACAACCCGATGACCAAGCGTTACCCGGACTTCAACAACGAAAAGAAGCCGGTCAAAGCCGAGCCGGGCGCTCAGG GCTACATCACTCAGGGTGCTAACGGCGGTCTGCCGGACAAGGTGCGTCACGGTGCGTTCGTGAACGTGCCTGAGT CTGTGCTCAAGGTGACGAAGTCCTGGACCGCTGCCAACCCGACGCACATCGAGGCTGTTGACTCCACCACCAAGG CCGTGTACAACGCCGGCACCCGCGAGCTCACCGCCACGGTGACCGCCGCCGATAAGGGCACGCTCGCCGGTTCGG TGAAGTTCTCTGCTGGCGACTGGTCCAAGACCGTGAAGCTCGACGCCGAAGGCAAGGCCACTGTGACCCTCCCGG CCAGCGTCTCTGGCACTGTTGCGGTTGCTTACGACGGCTACACCGATGGTTTGGTCAATCCATCCGATACTACGG TTGACGGCATTGAACAGGGCAAGGTCGATTTGGCTGAGCTCAACAAGCAGATCGCTGCCGCCGAAGCGCTCAAGG AATCCGACTACACGGCCGATTCCTGGGCCAAGCTTGCCGCCGCGCTGAAGACTGCCAAGGCCGCGCTCGCCGCTG AGAATCAGGGCGAGGTCGATACCGCCGCAGCCGACCTTAAGACCGCAATCGAAGCCCTGCAGAAGGCTCCGACCA ATCCGGGCGAAGGTGACGGAGATAAGGGCGACGGCAATAAGCCGACTACCCCGACCACCGGCGACAAGACCAACG TCAACAAGCCCGGCAGCGCGCTGAGCAATACCGGTACGGCCGTGCTCGGCCTGGGTGGTGCCGTGGTAGTACTCG CCATCGCCGGCATCTCCCTAACCCTCTGGCGCAAGCGTCGCGCCTGA

[0142] SEQ ID NO: 10 ATGGGAAAGCTGATACGAAAGGCAACCGGACTCACGGTCGGCGTGGCAACACTGCTCGCTGGTCTGGTGCTGCCG ATGACGGCCAGTGCCGAGAGCGCATCGCCAATCGATGCCAGTCCGATCATCCACTATTCATTCGATAACGCACTG ACGTCCAAGACCATCGCCAACGAGGGCAGCGCGGCCAACAGCGATGCCACCCTATCCGGCGACGCCACGGTGGCC AATGGCCAGATCAACCTGACCGGCTCGCAAACCATTAGCGTGCCGACCACGGCCATCGCCGGTAAGAAGGACGTC ACCGTCTCCATCTGGCTCAAGAACAATTACGGCAACGGCAATACCGCCGCCGCGTACATCGGCGCGGCCAAGACC GGCAATTATCCGGCCAACGGTTACTGGCTGCTCAACCCGGCCAACCCGAGTGGCTACGCGAAATCCGTAATGACC AATGCCACTGCGGCCGACCCGAATAACAGCCCGTGGGGCACCGAAGTCGGCCCTGGATCGACGAACGCCGCCATC ACCGGCACCAAGGCCACCAGCGATTTGGCTCTGTACACCACCGTCATCAACGGCACCAACAGCACTATGAGCTTC TACCTCAACGGCAAGCAGGTTGGAGACGCCACCTACGCCATTCCGGCCGGTGGCCTGACCAATTACGGCGATCTC GTCGCCTACATTGGCAAGTCCTCCTACGCTGACCCGAACTCCAAGCTCGACGTGGACGATTACGCCGTATACGAC ACTGCCATCAGCGCCGCAGACGTGACCAAGCTGTATGACGTTCAGGTGCTCGACAAGGCCGAGGCCGCTGTCAAG GCCGCTGTGCCCGCATCCGCTACCGAGGACTTCACCCTGCCGACCAGCGCCGCTGGTGTGAGCGTCGCGTGGAAG TCGGACAACGCAGCCATCGCCGTTGACAACGCCACCGGCAAGGCCACGGTCACTCGTCCGGCCGCAACCGCAGCT GATGCCGAGGTGACCCTCACCGTCACGTTCGGCAACAACGCCAAAACCGCCGCCTACACGGTCCTCGTGCCGAAG CAGCTCTCCGATGCCGAGCAAGCCAAGGCCGACCTTGACGCCATCACCATCGAGGACTCCGACGACATCCGTAGC AACTTCTCCGTGCCCACCAAGGGCAACAATGGTTCGACCATCTCGTGGGGAGTGACCGGTGGCAAGGATATCGCC ACACTAGGCGAAGGCGTGAGCGACAAATCTCGAACGGTCACTGTTAAGCGCCCTGCCGCCGGTAGCGATGCCGCC ACTGTGACGCTCAAAGCCACTGCCAAGTACGATACCGCCACTGAAACTAAGACCTTCACCGTCACCATTCAGCCG ATGCCTGCCGCCGAAGAGAAGGACGAGGCCTACGTGTGGGCGTTCTTCACCGGCGAGGGCGTGGGCGGCGAGAAA ATCAGCCTCGCGGCCTCCAAGGGCAACGATGCGCTCGACTGGAACACGCTGAACAACGGCACGCCGATATTCACT TCCGAGTTTGGCGAGAAGGGTTTGCGCGATCCGTTCATCATGAAGTCCAAGGACGGCGACAAGTTCTACATGCTC GCCACCGATCTGAAGATTGACGGTCGTGCCCCCCTCAACGGGCTGAATGGCTTTGCTGGTGCACAGGCTAACGGT TCCAAGTACATTGAGATCTGGAAGTCCGACGATCTGGTCAACTGGTCCAAGCAAAGCCACGTCAAAGTGAGCTCT GATTACGCAGGCAACACTTGGGCGCCTGAGGCCTACTACGACGAGGAAATCGGCAAGTACGTGGTCTATTGGGCC TCGAACCTGTACGACAACACCGACGAGAACAGCCGCAAGCAGCTGACCTACAACCGCATGGTGTACGTCACCACC GATGACTTCGTCAACTTCTCCGACCCGACAGTGTGGATTGACGTTGATCGCCGAGGCGGTGCAGGCAGTGGATCC ATCGATGTGACCGTGCAAAAGGTAGGGGATACCTACTACCGCATCTACAAAGATGAAAACACGATGTCTTTGCGT CAGGAGAAGTCCACAGATTTGACTGCCGCAATTGGTGGTGCCGGCGTGAAGAACTACGCCGATGCGCTTAAGGGT AGTGCATGGAGCGAAGTTGCCACGAACATCGGTAAAGGCCAGGCTAACGGTTACGGTAAAACCTTCACTTCCGGC GAAGGTCCATCGCTATTCAAGGCCAACGATGGCGATGTGAACGGCTACCAGTACTACCTGTTCGCCGACCAGCCG AGCTATCATCAAGGTCCAAACCACTATGTGCCGATGGCGACTGAGGATATCGCCAGCGGTCAGTGGACCGTTATC GGCAATAAGATGCCTGAGGCGAACTTCCCGACCAACTCCGATGGCGGCAAGCCGCGCCACGGAACCGTGCTGCCC GTGACCCGCGCCCAGTACCAGAAGGTGCTGGAGGCATACGCCCCGGCTGTGGCTGTGAAGTCCGTTGACGCGCTG TCTGCCGAGACAACGGTTGGTGTGGCTCCGACGCTGCCGGAGACCGCGCATCTGACTCATGCGGACGGTTCCGTT TCTGACGTTGCAGTTGAGTGGGATGCCATTGACGCATCTTTCTACGCCAAGACCGGCACCTTCACCGTCAAGGGC ATCACCCAAGACGATTCCCGTATGCCGGTTGAGGCTACCGTCATTGTGAACGGCATCGACCTCTCCAAGGCGACC GTCACCGTCGAACCCAACGAGTTCACCGCAGACGGCGCTGCCAAGGAACCAGCCGTGACCGTTGTACTCGATGGC GCGACGCTCAAGGAAGGCGCCGACTATACGGTGGCCTATACGAACAACGTCGAACCTGGCACTGCCACAGTGACC GTAACCGGCGCTGGCAAGTACTCCGGTACTGTCTCGGCAACGTTCACCATCAAGGCCGCCGAGCCCGGCTCCACG CTGGACAAGTCCAAGTTGCAGGCGCTTGTCGATAAGGTGAAGGGCTATAACAAGGCTGATTACCAGTCTGGTTGG GATGCTTTCGCCGTCGCGCTCGCCGACGCGCAGCAGGTGTTGCAGAACTCCACCGACCAGCAGGAAGTGGACAAG GCGTTGTCTCGGCTCCAGTCCGCCGTCGACAAGCTGGTCAAGAAGTCCGGCGATTCCGGCAAGACCGATGGCAAG GATGACGGCACGCAAAAGCCCGCCGCCAAGCCGGGCAGCGCTCTGTCCAACACCGGCGCCTCGGTGTTCGGTGTG GGTATCACCGCGGTCATACTGCTCGCCGCCGCCGGCGCCGCCTACGCCTTCCGCAAGCGCCGCGCCTGA

[0143] Suitably, the GH43_22 gene may encode a protein shown as SEQ ID NO: 11 or 12, or a sequence with at least 80% sequence identity to SEQ ID NO: 11 or 12. Preferably, the B. longum subsp. iuvenis strain comprises a GH43_22 gene encoding a protein shown as SEQ ID NO: 11 or a sequence with at least 80% sequence identity to SEQ ID NO: 11m and a GH43_22 gene encoding a protein shown as SEQ ID NO: 12, or a sequence with at least 80% sequence identity to SEQ ID NO: 12. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 11 or 12.

[0144] SEQ ID NO: 11 MKHWKKMAASLVAISTMMAWPTTYAMESEDSQPQTTDTATVQTTKAAEPTLLASWDFTGKNGTTNSAIADSTGK YNLTLKDGAKIEQYGDRSTNEALSLRGDGQYAQIDDQLFKDAGDSFTLEFASKTRHDDSGKFFSFIVGKDGSNDA NTTDQANANKYLMFYNSKTAIKGVISNNNWGNEQGSKVTVSGNDNSWADYKIWDGTNLAVFRNNALIIFKANTG IKMSDLGATTAYIGKSFYSVDEYWNGAMDDIKVYRGADLTMPTAVAISGTGWNNKLTLIEKDSTKLTATVTPDD AVS KN VT W S S S D E S VAKVAAD GT VT GVKAGT AT I TAT T E L GGVKAE L P VT VE PMNAQNAAAAD L DAAI AAL KVP A AENLPLVAKGTKNGSAITWKSSDEKLITSTNEKYENKTTGADDPYRGAGIINRPAYGDGDSKPVTLTATASYNGG EKVTKTIEVTVKEKTRIAPDTGYAAVTFESDSNGGEKAWVASTEKNDFFTFKTRNNGQAVLTNDADTGGLRDMFV LRSHEGDKYYLIATDLKVSSMGWSQNQVNGSRKVEVYESTDMMNWTRTNGDGNGGITINTPNAGMTWAPEAYWDD DLNAYWFFSSRMFTDDTRTTPVKNDKTGNSSYAQVRYAITRDFVNFTEPQMWQDTGYSRIDSTVRKIGGYYYRF TKNEQGGAAGDYITTGKSIFLERSKVLTAPTTEASPGQDPNTGWQLLEQALLPFEGPETIKLNKDDELNTKDDDG YILLSDNFAYRAFMTTGAELSKTTWDNPMTKRYPDFNNEKKPVKAEPGAQGYITQGANGGLPDKVRHGAFVNVPE SVLKVTKSWTAANPTHIEAVDSTTKAVYNAGTRELTATVTAADKGTLAGSVKFSAGDWSKTVKLDAEGKATVTLP ASVSGTVAVAYDGYTDGLVNPSDTTVDGIEQGKVDLAELNKQIAAAEALKESDYTADSWAKLAAALKTAKAALAA ENQGEVDTAAADLKTAIEALQKAPTNPGEGDGDKGDGNKPTTPTTGDKTNVNKPGSALSNTGTAVLGLGGAVWL AIAGISLTLWRKRRA SEQ ID NO: 12 MGKLIRKATGLTVGVATLLAGLVLPMTASAESASPIDASPIIHYSFDNALTSKTIANEGSAANSDATLSGDATVA NGQINLTGSQTISVPTTAIAGKKDVTVSIWLKNNYGNGNTAAAYIGAAKTGNYPANGYWLLNPANPSGYAKSVMT NATAADPNNSPWGTEVGPGSTNAAITGTKATSDLALYTTVINGTNSTMSFYLNGKQVGDATYAI PAGGLTNYGDL VAYIGKSSYADPNSKLDVDDYAVYDTAI SAADVTKLYDVQVLDKAEAAVKAAVPASATEDFTLPTSAAGVSVAWK SDNAAIAVDNATGKATVTRPAATAADAEVTLTVTFGNNAKTAAYTVLVPKQLSDAEQAKADLDAITIEDSDDIRS NFSVPTKGNNGSTISWGVTGGKDIATLGEGVSDKSRTVTVKRPAAGSDAATVTLKATAKYDTATETKTFTVTIQP MPAAEEKDEAYVWAFFTGEGVGGEKISLAASKGNDALDWNTLNNGTPIFTSEFGEKGLRDPFIMKSKDGDKFYML ATDLKIDGRAPLNGLNGFAGAQANGSKYIEIWKSDDLVNWSKQSHVKVSSDYAGNTWAPEAYYDEEIGKYWYWA SNLYDNTDENSRKQLTYNRMVYVTTDDFVNFSDPTVWIDVDRRGGAGSGSIDVTVQKVGDTYYRIYKDENTMSLR QEKSTDLTAAIGGAGVKNYADALKGSAWSEVATNIGKGQANGYGKTFTSGEGPSLFKANDGDVNGYQYYLFADQP SYHQGPNHYVPMATEDIASGQWTVIGNKMPEANFPTNSDGGKPRHGTVLPVTRAQYQKVLEAYAPAVAVKSVDAL SAETTVGVAPTLPETAHLTHADGSVSDVAVEWDAIDASFYAKTGTFTVKGITQDDSRMPVEATVIVNGIDLSKAT VTVEPNEFTADGAAKEPAVTWLDGATLKEGADYTVAYTNNVEPGTATVTVTGAGKYSGTVSATFTIKAAEPGST LDKSKLQALVDKVKGYNKADYQSGWDAFAVALADAQQVLQNSTDQQEVDKALSRLQSAVDKLVKKSGDSGKTDGK DDGTQKPAAKPGSALSNTGASVFGVGITAVILLAAAGAAYAFRKRRA

[0145] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 43_27 (GH43_27) gene. Suitably, the GH43_27 gene comprises SEQ ID NO: 13 or a sequence with at least 60% sequence identity to SEQ ID NO: 13. Suitably, the GH43_27 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 13.

[0146] SEQ ID NO: 13 ATGACAACCAAACCATCGATAGGCAAACGCCTGCTCGGCGCGATGCTGGCAGTGCCGATGGCGCTCGCCGGCATG GGAATCGGCGCGACCACGGCGGTCGCGGCCGATACCGTTCCGACCAATAATCTCATCGCCGCCTACGACTTCACC ACGAAGCCAAGTGACGGCAAGACCGTGGCCAACAGTGCGCCGAACGCTACGCTTGGCGCGGCCGAAGTACAGAAC TCCGCCGACTCGCTTTGGGCCGATGATGCCCTCACCCTTTCCGGCGGTGCCAAGACCGGCACCGGCGACTGGGTC AAGCTGCCCTCGAATCTGCTGTCCGGCAAGGACGCCGCCACGGTGCAGTTGGAGGTCAAAGCGGATTCCAGCATG CTCAATGCTTTCCATTTCCTGTGGAACATCGGTAACGACAGCTCCGATACGGAGTATTTCTTCGCCACGCTCAAC TGCGGCAGTTCGCGTAACCCGCTCGTCGGCCTGAAATCGGGCGGTACGGAGACGCTCGTGCAGTCCAGCTCCTGC GTGGCCAAGGCCGACCAATGGTTGTCGGTGACCGCCACCATTGATGGCACCGCCGCGAAACTGTACATCGACGGC ACGCAGGTGGCATCCGGCACCGTGCCGGCCAAACTGTCCAGCGTCAAGGACCAGTCGCTCAACACCATCGGCCGT TCGCCGTGGCCCGACAACCTGTTCAAGGGCGCGGTCTCGAACTTCCGCGTATACGATGCCGCGCTCACCGCCGAT CAGGTCGCCGCGATCAGCACTGCCGATGCCTCAATTCATGCCGGTGAACTCACCGGTTCCGTGCTGAACGGCATC ATCATCCCCACGACGGTCGACGATCCGTTCATTTCGCTGCCCACTGCGAACGGCGTGACGTGGGCGTCCTCCGAT AGCAGCGTCATCGCGACTGACGGCACGGTCAACCAGCCCGCCAAGGGCGAGGCAGCCAAGACTGTCACGCTGACC GCCGCCGTCACGATCCGTGGCCAGACCGCTACGAAGGAATTCACGGTCACAGTCAACCCGACCACGAAAACTGCC GCTGAACAGCTCAAGGAAGCCGCGGCCGGCTACGTGATCCCGTCCGTCGTGCGTTCCGGAGACGCCCTCCCGGCG GCTGTGAATGGCACTACCGTCACGGTTACGTCCACTAAGGACGTAGCCGTCGAGGATGGCAAGATCACCATCGAT GGCGACGAGGCCACGACCGGTACCATCACCGTCGAGTTCTCCAAGAACGGTCTCGCCGGCATCGAGCCCATTACC AAGGTCTTCACCGTAAAGGTGCTGCCCGCCGCGAAGTCCGCGACCATCGCCGCCTATGATTGCAACGCCACCAGC GCCGACGAGGCCAACAACGGCGACATCGCCTACAGCATGCACCTCGCGTTGCAGAACGCTGACGGTTCGTACACC CCGTACAACGAGAATTACGGTATCTTCTTCGCACGTTCGCCGAAGGCGCAGAATCTCAACGAGAACCTCGACGGC AATGATTACCGCAGTCTCAAGGATCCGAGCCTGCTCCGCATGGCCGACGGCACCTATGGCGTGATTTCCGTGCGT ACCAACCGCGGCACCGCCACCGGTGACTCCACCGCGAAGTCCAGCGTGCTCATCGCCACCTCCGAAGACCTGCTC ACCTATAGCGAACAGGAGAACTCCGGTTCCATCGTCGACCTTGGCGAGACCAACGGCGTCAACGCTCCGTACGCC GTGTACGACACCGCCAGCAAGCAGTATGTTGTCGGCTGGGCCGATGACAACGGCGTGGCCAAGTACACCACGTTC GATTCGCTCAAGGGCTCCGCGTCCAAGCATGGCAGCGTACTGTACGGTTCCATCGCCAAGTCCGGCGTACTCGAT GCCGACGGCGTGCAGGGCATCGCGAACTTCCGCTCCGGTGCCACCATCGCGGTGGACGAGGCGACCGTCAAGGCG CTCAACACCCGTTACGGCCGCTCTGAGAACACCGGCACGAGCAATCTCACTGACATCACCGTCGAGAAAGGTTCC TCGATTGATGAGATGACCTCGCAGCTGCCGAAGAACGTGGACCTCACTTACTCCGACGGTTCTACCGGCTCCCTG CCGATTTCCTCATGGAACACTGAGGGTATAGATCTGACGAAGGTGGGTGATTACACTGTCACCGGCACCGTCAAG CAGACCGAATACCAGATTCCGTTCGCCGAGGACCGCGCCGATCCATCGGTGTATAAGTGGCAGTGGACGCATGAG GTCGACGGCAAGGAAGTCACCGAAACCAAGTTCCTGATGATCGCTTCCAACGACATCCAAGGTGATGTCACTTGG CAGCATGGTTCGCCCCACATGCCGTTCCGCATGGCCGACACGATTTCCGGTCTCGCCGACGAGCCGGGCAACCCG AATGCCCTGATTCAGTCGAACGGCTACAACAACAAGGAGGTGTCGCTGCTCAAGGCTGGCGACAAGGACTCCGAG GGTAATGCCATCATGCACAGCTTCTGGGCTCCAGAAATTCATGAGATTGATGGTAGGCTCACGATTCTGTTCATG GCCGGATACGGCAACACATGGTCCAACGGCAAGTCGGTGTACATGCAGCTCAAGCAGGATGCCGACGGTCATGAC CTCGACCCGACCGACCCCGATAACTGGACTGTGCCGACACCGATCTACCGCAATGACGCCTCGCTGCTCAACGGT AACAAGCAGCTCGCAGCCACAGCGTCCGGCGGAGTGGGCATGTCGCTCGACATGACCTATTTCCAGGATGCCGAC GGCAGGTCCTACTACGCCTGGCAGCAGCTCGGCGCCACCTACATCGCCACGATGGATCCGAAGGACCCGGCCCAT GTGACCAGCTCCCCGGTGCGCATCGTCACCCCGGAGTATGCGTGGAACGCCGCCATAGCCGAAGGTCCGAACGTG ACCCTGCGCGACGGCAAGCTGTACCTCATGTTCTCCGGTTCCGGCGTGGGTAAGACATACACCACTGGGCTGGCC GTAGCGGATGCCTCCGGTACTGACCTGACCGACCCGGCCAGTTGGACGGTGCTCAACTACCCGATTCAGAAGTCC GGTCCGTTCAACGGTGAGATGCAGCTCGGCACCGGTCACGGCATGTGGAGCGAGGACGAAGATGGCAACCAGATC TACGTGTTCCACGCCTATGCCACGAAGAATCTCGGATCCGTGAATGCTGCCGGCCGCGACATGTTCGTGCGCCGT GTGCACTGGGCCGCCGACGGCATGCCGGTGTTCGACATGAGCTCTTCCGAGGAGCTGGCGAACAAGATCGTTTCC GTTACGGTGCATGTGGTTGACGATGCGGTTGCGGTCGATAAGTCTGGTTTGTCCAAGGCGCTTGCGTCCGCCAAG CAGCTGCACGGGTCCGACTACACCGCCGCCTCGTGGAAGGCGTTTGCCACGATGCTGGCCTCCGCTGAGAAGGTC TATGCCGACGATACTGCTACGCAGAAGGACGTCGATGACACGACCGTCGCGTTGGTCAAGGCGCAGGCTGCGTTA GTGAAGATTGATGGTTCCGATTCAGGCGATGGCTCGGGCGATTCGACTAAGCCGAGCGACGGTTCGAGCGTCGAT GCGGGAGATAAGACGTGCAACAATCTTGGTTTGTCCAAGACCGGTGCGGCTGTGCTTAGTCTTAGCGGCGTAGCC GTGGCGCTTGCTGTCGCCGGTATCGCTCTGACTCTCCAGCGCAAGCGTCGCGCCTGA

[0147] Suitably, the GH43_27 gene may encode a protein shown as SEQ ID NO: 14 or a sequence with at least 80% sequence identity to SEQ ID NO: 14. Suitably, the protein may comprise a

[0148] 1 sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 14.

[0149] SEQ ID NO: 14 MTTKPSIGKRLLGAMLAVPMALAGMGIGATTAVAADTVPTNNLIAAYDFTTKPSDGKTVANSAPNATLGAAEVQN SADSLWADDALTLSGGAKTGTGDWVKLPSNLLSGKDAATVQLEVKADSSMLNAFHFLWNIGNDSSDTEYFFATLN CGSSRNPLVGLKSGGTETLVQSSSCVAKADQWLSVTATIDGTAAKLYIDGTQVASGTVPAKLSSVKDQSLNTIGR SPWPDNLFKGAVSNFRVYDAALTADQVAAISTADASIHAGELTGSVLNGIIIPTTVDDPFISLPTANGVTWASSD SSVIATDGTVNQPAKGEAAKTVTLTAAVTIRGQTATKEFTVTVNPTTKTAAEQLKEAAAGYVIPSWRSGDALPA AVNGTTVTVTSTKDVAVEDGKITIDGDEATTGTITVEFSKNGLAGIEPITKVFTVKVLPAAKSATIAAYDCNATS ADEANNGDIAYSMHLALQNADGSYTPYNENYGIFFARSPKAQNLNENLDGNDYRSLKDPSLLRMADGTYGVISVR TNRGTATGDSTAKSSVLIATSEDLLTYSEQENSGSIVDLGETNGVNAPYAVYDTASKQYWGWADDNGVAKYTTF DSLKGSASKHGSVLYGSIAKSGVLDADGVQGIANFRSGATIAVDEATVKALNTRYGRSENTGTSNLTDITVEKGS SIDEMTSQLPKNVDLTYSDGSTGSLPISSWNTEGIDLTKVGDYTVTGTVKQTEYQIPFAEDRADPSVYKWQWTHE VDGKEVTETKFLMIASNDIQGDVTWQHGSPHMPFRMADTISGLADEPGNPNALIQSNGYNNKEVSLLKAGDKDSE GNAIMHSFWAPEIHEIDGRLTILFMAGYGNTWSNGKSVYMQLKQDADGHDLDPTDPDNWTVPTPIYRNDASLLNG NKQLAATASGGVGMSLDMTYFQDADGRSYYAWQQLGATYIATMDPKDPAHVTSSPVRIVTPEYAWNAAIAEGPNV TLRDGKLYLMFSGSGVGKTYTTGLAVADASGTDLTDPASWTVLNYPIQKSGPFNGEMQLGTGHGMWSEDEDGNQI YVFHAYATKNLGSVNAAGRDMFVRRVHWAADGMPVFDMSSSEELANKIVSVTVHWDDAVAVDKSGLSKALASAK QLHGSDYTAASWKAFATMLASAEKVYADDTATQKDVDDTTVALVKAQAALVKIDGSDSGDGSGDSTKPSDGSSVD AGDKTCNNLGLSKTGAAVLSLSGVAVALAVAGIALTLQRKRRA

[0150] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 43_29 (GH43_29) gene. Suitably, the GH43_29 gene comprises SEQ ID NO: 15 or a sequence with at least 60% sequence identity to SEQ ID NO: 15. Suitably, the GH43_29 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 15.

[0151] SEQ ID NO: 15 ATGAGTTTCCATGTATCCGCGCAATCGGTTCGCGCGGTGGCCGGTGGACTCGTCGCCGCAGCGACATTGCTGTCA GGCCTTGCCCTTGCGCCGACCGCAATGGCCGCCGATTCAGCCACCGCTGACAACGCGCCCAGCGTTGCCGGTCAC GCGTATAACGAACTGCCGTATAACAATCCTGATGTCACCGTCACCCAAATCGACAATAGCGCACTGCCCAGCTAC ATGCGCAACCCCATCGGGCAGAACGAGGGTATTGACACCCCGAACGATCTTTCGCAGAACTACTACTCTGCAGAT GCATCCGCGCTGAGCTATGACGGCAAACTCTTCGTCTTCACCGGTCACGATGAGGCTTCGCCCGACTACGGCTCC TTCAACATGAAGGACTGGGGCGTATACGTCACCGATGAAGACGGCCTGAATCAAGGCAAATGGACACATTACAAG ACCATCGCCAAGGCAGACCTGTTCAGCTGGGCCACCGGCGATGGCGCGTACGCCGGCCAAGTCGTAGCCGACGAT AACGGCACCCCGAGCGACACTTCCGATGATTGGTTCTACTACTACGTGCCGGTGAAGGACAAGGCTTCTGAGGCG GCTGGACAGGACCCGTTCGCCATCGGCGTGGCCAAGTCGAAGAGTCCGCTCGGCCCGTGGAAGGATACCATCGGC AAGCCGCTGCTCACCACATCGCAAACCCAGATTGAAACCATCGATCCGGCATTCTTTGTGGACGAGGATGGCACC GGATATTTGCACTTTGGTACGTTCGGCACTCAGCTCGCCATCAAGATGAAGAAGGACGCCACAACCGGCCGCACC TCATACACCGAGGTGGAAACCAAGGCTGATGGCACCACGCCGAACCTCCACACCATGAAGGACGCGGACAGCAAC GCGAACGGCCCGAAGGGATTCTTCGAGGCGGCGTGGGTGTTCCGTAAGGGCGATACCTATTACAACGTGTACGAC GGCGGTAAGCCCGGTTCGGGCACGGCCACCTGCGTGGAATCGAACTATCAAGCTTGCATCCAGTACTCCACTTCC GACAGCCCGCTCGGCCCATGGAAGTACCAAGGCGTAATCGTGCCTTCTGGCTCGGCCACCACGATGCACCCCTCG GTGCTCCAGTTCGGCGACAAATGGTATGTGACCTATCACACCGGCGACAAGGAAGGCGGCACCGATTTCCGCCGT GCCGTGTGCATTGATGAAGTCGATTGGACCGCCGACGGCCAGATGGTTTCCACCGCCCATCCAACCAAGGCCGAG AAAACGCAGCCCTCCACCAACGTGGCTCCGTACGCAAAGGTGAGCGCCACGTTCACTGAAACGCCTGCTTGGAAG GGTTCGGTGAACGACGGCCGTGTGTTGCAAACCGCTGTGGTCCCGCCGAATCACTGGACCAACTACCGTTCTATC CCGCAATCGCAGTCCGGCGATTCTCTGGTCTACCAATGGGATGGCACTGTGCGCGTCAACTCGTCTAAGGTTTGG TTCGACGTGGATTCCAACGCTCTGCGCGCGCCCGCCTCGTGGAAGATTCAGTACTTGGACGCGGACGGCACATGG AAGGATGTCATCAACCCGAGTGCCTATACAACGACCACAGGCAAGGCCAACCCCAACGCCGTCACCTTCGATGCG GTGACCACTACTGCCTTAAAGCTCGACATGACCGGTCAAGCTGTGGATGGCGGCTATGCCTCCGTGGCCGTTGCT GAATGGGAAGTCGGCTCCGACTCCAGCGAATCGCCGGCAATCACTGCGCCGAAGAGCGTGACCACCGCCACCGGT ACTGCGCCTACTCTGCCGGCCACAGTGGATGTGAAGTACGGGAACCCAACCGTTGCCTCCCCAGTAATTTGGCGT CCAGTTGATGCTTCCTCGTATGCCAAGGTCGGTTCGTTTACGGCCTACGGCGTGGTCGCCGGCGTGCCCGGTGAG GCAAGCGAGCAGGGCAATGTGTCGGTAAATGTCACCGTGCAGGACGGCTACCAGCCTGCCGCTGATACCACGAAG CCGACTGTAACCGTTGCCGTTACTGCTAACGCAGGCAATAGCGAGTGGCTCACCACCGCTCCGTTCGCCACCGTG CAGGCCACGGACGACACCGCACCTATCGCCAAGCTGGAGATTTCCGCTGATCAAGGCAAGAGCTGGACCACCATC GCCGCGAATGCAAACGCGGCCATTGCCACGCTTTCCCAGCAGGGCGATGTCGAAGTGTGGGCTCGCGCCACCGAT CAGGCCGGCAACGTTTCCGACGTGGCCAAGGCCGGCGGCAAGGTGGACTCCGCCGCGCCAACCGTGACCGCCGCC GCCGATAAGGAGGAGCGCACGCTGACCTTGACCGCTGATGACGGCACCGGTTCCGGTGTCGCATCAATTGAATAC CGCATTGGCACAGACGGTCAATGGGCCACGTACAGCAAGCCGATTGCTGCACCGAGCGCGTCGCGCGCCACCGTG TACTACCGCGCCACCGATAAGGCCGGCAACGTGTCCGCTTCGGCGAAAACCGACATTCCATCCGACACTTCCGTG CCGCTGACCGGCTACATTGAGGGCGATGCCACCGCCACCGATGTGGACGGCAAGGCATCCGGCTGGGTCAAGGGT GCCGCCGCGTTGAACGACGGCAAGATCATTCCCGATATCACCATTGCCAACGAGGATGTCTGGGGCACTTGGCCC AACACCGGTGAGATGCGCCTCGACTACGAGTGGGACCGTGAAGTGACTATCGACTCTAGCCGCGTGCAATTCACC TCGGATGATGGCGGATTGGGTATTCCGGCATCGTGGGAATTGCAGTACTGGGACGCCTTGGCGAACAACGGTGCC GGCAACTTCGTGGATATTCCCGACGCCACCTACACTGTGACCGCCAATTCACCGTCTGCTGGCTGGGCCACCGGC GATGCCAAGGGGTGGTCTGATGGCACGTGGAACACTCCGGTCAAGACTACCAAGTTGCGTATGGTTATCACGTCC GGCTCGGCTTCTCCGGCTGTTGCCGAATGGCAGGTTCATGCCATTGACGACAGTACGCCTGAGCCGCCTGAGCCC ACACCGATCGACAAGACCGAGCTCAAGCAGGCGCTCGCTGACTCGCCTAAGGCTGACGATGCCTCCAAGTACACC GAGACTTCATGGGCGGAGTACGCGGCGGTATTGGATTCGGCGCAGCAGGTGTATAAGGCTGAGGATGCCACCGAA GCTGCGGTGGTGGATGCCGCAACCCAGCTGAAGCAGGCAGCGAAGAAGCTGGTGCTTGTAGCTACGGTGCAAGAT CGTGCCGCGCTGAGCGCTCAGCTCGATGCCGCTGCTGCCGTGGATCGCACAAAGTGGACTGATGAATCGCTGGCC GTGCTTGATTCGGCAGTCGCTACGGCGAATGCGCTGACGAGTGATGGTCAGGCCGCCCAGTCTGACGTACAGGCT GCGACTGAGGCAATCAGCGATGCCATCGCGGGTCTGGTTGAGAAGAGCACCACGAAGCCTGGCCAGGGTGGCGAT AAGCCCGGTTCCGGCACGGACAAGCCCAACCAAGGCAACGATTCCAACCAGAACAAGGGTGATGCAGACTCCGGC AAGCACAAGAAGATACCTGACACCGGTGCAGCCGTGCTTGGTGTTGGCATCCTCGCCGTGGTACTTGCTGTTGCG GGTGTAATCATCCTCAAGCGCCGCAAGTCCGGTACCTGCTAG

[0152] Suitably, the GH43_29 gene may encode a protein shown as SEQ ID NO: 16 or a sequence with at least 80% sequence identity to SEQ ID NO: 16. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 16.

[0153] SEQ ID NO: 16 MSFHVSAQSVRAVAGGLVAAATLLSGLALAPTAMAADSATADNAPSVAGHAYNELPYNNPDVTVTQIDNSALPSY MRNPIGQNEGIDTPNDLSQNYYSADASALSYDGKLFVFTGHDEASPDYGSFNMKDWGVYVTDEDGLNQGKWTHYK TIAKADLFSWATGDGAYAGQWADDNGTPSDTSDDWFYYYVPVKDKASEAAGQDPFAIGVAKSKSPLGPWKDTIG KPLLTTSQTQIETIDPAFFVDEDGTGYLHFGTFGTQLAIKMKKDATTGRTSYTEVETKADGTTPNLHTMKDADSN ANGPKGFFEAAWVFRKGDTYYNVYDGGKPGSGTATCVESNYQACIQYSTSDSPLGPWKYQGVIVPSGSATTMHPS VLQFGDKWYVTYHTGDKEGGTDFRRAVCIDEVDWTADGQMVSTAHPTKAEKTQPSTNVAPYAKVSATFTETPAWK GSVNDGRVLQTAWPPNHWTNYRSIPQSQSGDSLVYQWDGTVRVNSSKVWFDVDSNALRAPASWKIQYLDADGTW KDVINPSAYTTTTGKANPNAVTFDAVTTTALKLDMTGQAVDGGYASVAVAEWEVGSDSSESPAITAPKSVTTATG TAPTLPATVDVKYGNPTVASPVIWRPVDASSYAKVGSFTAYGWAGVPGEASEQGNVSVNVTVQDGYQPAADTTK PTVTVAVTANAGNSEWLTTAPFATVQATDDTAPIAKLEISADQGKSWTTIAANANAAIATLSQQGDVEVWARATD QAGNVSDVAKAGGKVDSAAPTVTAAADKEERTLTLTADDGTGSGVASIEYRIGTDGQWATYSKPIAAPSASRATV YYRATDKAGNVSASAKTDIPSDTSVPLTGYIEGDATATDVDGKASGWVKGAAALNDGKIIPDITIANEDVWGTWP NTGEMRLDYEWDREVTIDSSRVQFTSDDGGLGIPASWELQYWDALANNGAGNFVDIPDATYTVTANSPSAGWATG DAK GW SDGTWNTPVKT T KL RMVI T S G S AS P AVAEWQ VHAI DDSTPEPPEPTPIDKTEL KQALAD S P KAD DAS K YT ETSWAEYAAVLDSAQQVYKAEDATEAAWDAATQLKQAAKKLVLVATVQDRAALSAQLDAAAAVDRTKWTDESLA VLDSAVATANALTSDGQAAQSDVQAATEAISDAIAGLVEKSTTKPGQGGDKPGSGTDKPNQGNDSNQNKGDADSG KH KK I P DT GAAVL GVG I LAWLAVAGVI ILKRRKSGTC

[0154] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 121 (GH121) gene. Suitably, the GH121 gene comprises SEQ ID NO: 17 or a sequence with at least 60% sequence identity to SEQ ID NO: 17. Suitably, the GH121 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 17. SEQ ID NO: 17 ATGCATCAATCAACACGAAAGCGGTGGCTTGCGTCAATCGGCGCGGTTGCAGCGGTCGCCACACTGGCCACCGGC GGTGCAGTCACCGCGCAGGCAGCCGATGCGCCCGTCATCAAGAATGCGGATGTGGCATATCCGTCGTTCAAGGGA TCTGATGATCCGATGAAGACGGCGGCGAACAACACCACATATAACCCTGCCGTCAGCTATCTGCAGGAGACATTC GATAACGACGTGAAGAACCTGGCCGGCATCGACACCGACCATGACTTCTGGATCGATAAGATTCTCACCCGTACT GGTGCACAGCCAACTGGTAAAGGCACGAACGACAAGGGTGCTTACTCGTATGAAGGCTCCGACGGCAACAACTAC CTGTTCACCCGTGGTCGCGCCGCCTACATGTACACGCACACGCCTAATCAGCTCGGTTTTGTGGGTGATACCGCC TACTGGGACCAGACCAGCAGGAGCGGCTTCACCGTTACCGTAAACGCTGATGGATCAAACCAGACCCTTAACGAA GACGCCTCCCAGCGCAAGCAGACGCCGAGCTACTTCACCTCCCTGTTCCAGACCGGTGGCAAGAGCCTCAAGATC AAGGAAGTCAAGTACATCACCTACAACAACGTGATGGTTGCGAACCTCACCGTGGAAAGCACGCAGGACCGCGAT GTCACACTGACCACGGCCTCGCCGTTCGCCGCCGAGGGTGCTGATGGTGCCACCGAACTTACTGGCCGCGTGAAC GTCAAGAACAACCTGACGACCATCTATCCGCGCTTCTCCGCCAACAACCAGGACGGTTCCAACTGGATCGTCAGC GGTGGCAAACTCACCAGCACGTTGAGCCTCAAGGCCAACGAACCGCAGACCGTCAAGATTCAGCTCGGCCTGATC GCCAACGAACTGCCTGACTCCACCAAGGAATATGAGGCCCGTTACACCGGCGACCTTAAGGATGCTGCCGCCTCC TACAAGGATTCCGTGACCACCTACAACAAGTGGTGGGTCGATAACGCTCCCTACGTGGACACTCCGGAAGACAAT ATCGATAAGACCGTGGTCTACCGCTGGTGGCTGAGCCGTTTCAACATGCTCGACGCCAACATGCCTGGCAACACC TTCCAGTACCCGACCTCCATCGAGGGTGTGCTCGGCTACAACAACCAAATCGTGCTCACCTCCGGCATGTTCATG ATGGACCCCAAGTGGTTCCGCAACCCCGAGTACTCCTACGGCACCTGGCTTTCCGCCGGCGATACCGCCAAGAAG AGCAAGGCGGGCTATTACTACTACCACGACAATCCGGGCGACCCGGCCAACTGGAACCATAGCTACACGCAGTAC ATCACGCGCGCCGGCTGGGACTCCTACAAGGTGCACGGCGGTCCGTCCACCGTGGCCGAGGAGCTGGCCGACCAG GGTGCCGAGGACGTGCAAGGTCTACTCGCTTCCAAGAGCGAGCCGGACAACAACGACAACCAGAACAACAATGAC AACAGCTTGATTGACTGGTCCTGGTGGTCGATGACCGGTAACGATGCCGACGCCGTTTCCTTCTCTGAGCCGGGT CGCTCCGGCCAGCGCATGGATCGCGCCGATGGTTCCGCCAATATGTGGGCCAACGCCAATGCGGCTGCTCAGGCC TACAAGGCCGCTGGCGATACCGCCAACGCCGAGAAGATGCAGGCCATCGCCGACAAGATCCAGAAAGAAGTCACC ACTGAACTGTGGGACAAGTCCGACAACCTGCTCAAGCACAAGTGGCTGAACGACGGTGCTTTCGCCAAGTACAAG GAGATCAATAACTACTACCCGTACTCCGAAGGCCTGATGCCTACCGGCAACGAAGATTACAACAAGGCTCTGCGC CTGTTCGAGGATTCCAACGAGTTCCCGATCTTCCCGTTCTTCACCGCCAACCAGGCGGACAAGGCGGCGCTGAAC TTCCCCGGTTCCAACAACTTCTCCATTATCAACGCACAGCCGCTGCTGCAGGTCTATTCAGCCGGCATCCGCAAT TACGATGCAGCCAAGAACGGTTACATCACCAATGAGCAGTTCAAGAAACTGCTGTACTGGGTGGCGTTCGCGCAC TATCAGGGCGGCGATAACAACTACCTTGATCAAAACGAGTTCTGGAACGAGGATAACAACAACGTCGGCGATGTA AACGGTGACGGCGTGATCAACAACCTCGACAAGAACCTTGACGCCGCACAGAACGGCGGCAAGATCACCTACCGC TCCTGGATCCACCACACCCAGCTCGGCACCACGAACTGGACGATGGTCGAGGACGTAGCCGGTATGGTGCCGCGC GAGGATAACAAGATTGAGCTGAACCCGATTGAGATCCCCGGCTGGAACTACTTCACGGTGAACAACCTGAGCTAC CACGGTCAAGATGTTTCCATCGTGTGGGATAAGGACGGCAGCCACTATGGTGGACCTGCTGGCTACAGCCTGTAC GTGGGGGGCAAGCTCGCCTTCACTTCCGACAAGCTCGCACACCTCATTTACGATCCGTCCACGGGCACCGTTGAG GATGCCGACAAGGCCGGCGTAACCATCACCAATGCCGCTGGTTCTGATATCAAGGCCGCCAACCAGGTTGCCTTC ACCGCCGACCAGCGTGTGACCGACCTGTTCGCCAAGTCCGGTGCCAACGTCGACTCCGCTTCCAAGTCCACCACG AATGTGGCCAAGGACGCGGACGTGACCGGTACCACCTACGCCGAGAAGGACACCAACTACCCGGCCAAGAACGCG GTGGACGGCAAGACCGTGATGGAATCGTTCTGGGGTACCAAGGGTTCTGAGAACAAGACCGACACGCTCAATATC AAGTTCAAGGACGGCAAGCAGAAGATCGACGACCTCCGCTTGTACTTCTACCAGAGCTCGTCCAGCCAGACCATC TCCGGCTATGCCGAGCCCGCCAACTACAAGTTGGAGTACCAGAAGGATGACGGCACATGGGCCCCGATTGCGGAT CAGGTGCGCACCCCGAACTACGCGGGCGCGAACTACAACCGTATCCAGTTCACTCCGGTGGAGACCACGACTATC CGCGTCACCTTCACGCCGCAGGCCGGCATGGCCGTCGGTGTCAAGGAGATCGAAGCCTACAACACCGGTATCAAG GCTGACGGCACTTCCGAGAACCAGGCTCCGCAGGTGGATGCTTACGTGTCTTCCAGCACCTCATCCGGTGCCAAG CTCGTCGGTACGGTGAAGGATGACGGTCTGCCCGCAGAAGGCGACGTCACCACCAAGTGGGAGCTGGTTTCCGGC CCCGAGGGCGGTACCGCGAAGTTCGTGGACGATACTGCTGCCAGCACCACCGTCACCTTCAACAAGGAAGGCGAC TACGTTCTGAAGCTCACCGCTTCCGATGGCGAGAAGGAAGGCTCCAAGGAAATCACCGTTCACGGCATCCCCTCT GACGGTACCGTGAACGTAGCCCCGCAGTCGAGCGCCTCTGCCAGCTACACCAACGGCTACCAGCCGAAGGACAAC GCCAAGAAGGTCATCGACGGTCAGGTGGTATACACCAACACGCCGAACGAGACCTGGAACAACTGGGGCGACAAC ACTGGTGTGGAGCCGTGGCTGCAACTGAAGTGGGCCGGCAAGGTGCCACTGAAGAAGGCCAAGGTCTTCTTCTGG ACCGATGGCGGTGGCGTGCCGATGGCCTCATCTTGGAAGCTCCAGTACGCTGACGCTGACGGTAACTGGCAGGAT GTGAAGCTGGCTGACGGCCAGTCCTACACGGTCAATCAGAACGAAGGCAACGAAGTGAAGTTCGCCGACACCGTC GAAACCGACAAGCTGCGCGTGGTCTTCCCGAAGGGCGCCATCGTGGGTGCTTCCGAGTTCGAGGCGTACGCCATC GAGCCGGTGAGCGTGGACGAAGTCAACCGACTGGTGCAGACCGGTTCCAAGGCCGATGATCTGAAGCTGCCCTCC ACCGTGAGCGCCGTATACACCGACGGTTCTCGCCGTGACCTCGCCGTCACGTGGGATAAGGTGACCGACGCTCAG CTGGCCGCCGATGCCGTATTCGATGTCAAGGGCATCGTCGCTGGTGCGCTGAGCGGTACGGTTGCACACATCGCA GCTCGTTCCGATACCGCATTGCAGACCGTGGGTAATGCGCAGCCGGTTGAGCAGACCGTCTACCAGAACGCCAAG TCCATCGACCTGCCCGCCACGGTTCCGGTGAAGTTCCCGAACGGATACAACGACGACCGCAAGGTCACGTGGAAG GATGCCGACATCAAGGCCATCGACCTGACCAAGGTTGGTGACTACGAGGTGGCTGGTACCGTCGACGACGGTTCG TCTTCCGCAGCTGCCAAGCTCACTGTCCACGTGGTTGCCGACCCGAACGGTTCCTCCACTCCTGAGCCTGAGCCT GAGCCGTTGGTCGGTTGGATTGAAGGCAAGGCGACCAAGACCACCATTTCGCCTGATTCCGAGGCGACCTGGTCA CCGGCCGAAGGCAAGCTCAACGACGGCGTAGTCGTCGATGATACTTGGCCGACCACGGATGATCAGAACGTCAAC GACAAGGTCTGGGGTTCTTGGGGCAAGGCAAAGGACGGCATGTACGCCCAGTACGACTTCGGTCAGTCCGTGACC GTTGACCAGAGCCGCGCCCAGTTCTGGGCCAACTTCGCTGAGACTGACGATTCGAAGGGTGGTCTGGAAGTCCCG GACGCTTGGAAGATTCAGTACCTCGCCGAGGATGGTTCTTGGAAGGATGTCGAGCCCACCGAGGATTACACCATT GTGCGTAACTCGCCGGCTTCTCGTGCGGATACCGATGCCAAAGGTTGGAGCACTGTGACCTTCAAGCCGGTCGCC ACCAAGTCGCTGCGACTCGTGCTCACTCCGCACACCGGCAGCAGCACCTTCGGGGCCGCCGTGGCCGAGTGGGGC GTGCATGGTATTGACGGCACCGAGCCTGAACCTACCCCGGTCGACAAGACCGCGCTCGAGTCGGCTCTTGACACA GCCAACGGCCTCGATGCAAGCCGCTACACCGCCGCTTCATGGGCTGAGTTCCAGCAAATCATTGACGCTGCCCAG GCTGTGTACGACGATGCCAACGCCACCGCAGAACAGGTCGCCGAGCAGGTGACCAAGCTCGAGGACGGCCAGAAG GCACTCGTTGCGCTCGCCACCGACGTGGAGAAGTCCACGTTGCAGGCGGCCATCGATGCGGCCAAAGCCGAGGCC GCTTCCGGCAAGTACACGGATAAGAGTGTCGAGGCCTTGAACAAGGCCATCGAGGCTGCGGAAGGTGTGCTCAAG GTCGGTGAGGTCGGTGAGGTCACTCAGGCCGCCGTCCAGGAAGCGTCCGCTTCGCTGAACAAGGCCGTCAAGGCC TTGGAAGAGAAGCCCGCCGCCGAAACGGTGAAGAAGGAGTCCCTCGAGGCTTCCATCGAGCAGGCCAAGAAGGCT GACAAGTCGAAGTACACCGAGGAGGCATGGCAGGCTCTGCAGAGCCAGATTGCCGCCGCTCAGAAGGTGTACGAC GACAAGGATGCCAAGCAGGCCGATGTCGATGCCGCACAGGATGCCCTTGACAAGGCATTTTGGGCCACCAAGGTT GAGCAGAAGCCCGGCTCCCAGCAGCCTGGTGTGACCGACACTGATAAGGATGATAAGGACAACAAGGGTGATCGT GTGCCTCCGACTGGTGCCGCGGTTTCCGTAGTTGCTGCGGCTGCCGTGCTGCTCACCGCCGCAGGCGTGACCATC CTGAAGCGTCGCCAGTCCGGCGACCACGGTTCGGCTCGCCACTCGGCCTGA

[0155] Suitably, the GH121 gene may encode a protein shown as SEQ ID NO: 18 or a sequence with at least 80% sequence identity to SEQ ID NO: 18. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 18.

[0156] SEQ ID NO: 18 MHQSTRKRWLASIGAVAAVATLATGGAVTAQAADAPVIKNADVAYPSFKGSDDPMKTAANNTTYNPAVSYLQETF DNDVKNLAGIDTDHDFWIDKILTRTGAQPTGKGTNDKGAYSYEGSDGNNYLFTRGRAAYMYTHTPNQLGFVGDTA YWDQTSRSGFTVTVNADGSNQTLNEDASQRKQTPSYFTSLFQTGGKSLKIKEVKYITYNNVMVANLTVESTQDRD VTLTTASPFAAEGADGATELTGRVNVKNNLTTIYPRFSANNQDGSNWIVSGGKLTSTLSLKANEPQTVKIQLGLI ANELPDSTKEYEARYTGDLKDAAASYKDSVTTYNKWWVDNAPYVDTPEDNIDKTWYRWWLSRFNMLDANMPGNT FQYPTSIEGVLGYNNQIVLTSGMFMMDPKWFRNPEYSYGTWLSAGDTAKKSKAGYYYYHDNPGDPANWNHSYTQY ITRAGWDSYKVHGGPSTVAEELADQGAEDVQGLLASKSEPDNNDNQNNNDNSLIDWSWWSMTGNDADAVSFSEPG RSGQRMDRADGSANMWANANAAAQAYKAAGDTANAEKMQAIADKIQKEVTTELWDKSDNLLKHKWLNDGAFAKYK EINNYYPYSEGLMPTGNEDYNKALRLFEDSNEFPIFPFFTANQADKAALNFPGSNNFSIINAQPLLQVYSAGIRN YDAAKNGYITNEQFKKLLYWVAFAHYQGGDNNYLDQNEFWNEDNNNVGDVNGDGVINNLDKNLDAAQNGGKITYR SWIHHTQLGTTNWTMVEDVAGMVPREDNKIELNPIEIPGWNYFTVNNLSYHGQDVSIVWDKDGSHYGGPAGYSLY VGGKLAFTSDKLAHLIYDPSTGTVEDADKAGVTITNAAGSDIKAANQVAFTADQRVTDLFAKSGANVDSASKSTT NVAKDADVTGTTYAEKDTNYPAKNAVDGKTVMESFWGTKGSENKTDTLNIKFKDGKQKIDDLRLYFYQSSSSQTI SGYAEPANYKLEYQKDDGTWAPIADQVRTPNYAGANYNRIQFTPVETTTIRVTFTPQAGMAVGVKEIEAYNTGIK ADGTSENQAPQVDAYVSSSTSSGAKLVGTVKDDGLPAEGDVTTKWELVSGPEGGTAKFVDDTAASTTVTFNKEGD YVLKLTASDGEKEGSKEITVHGIPSDGTVNVAPQSSASASYTNGYQPKDNAKKVIDGQWYTNTPNETWNNWGDN TGVEPWLQLKWAGKVPLKKAKVFFWTDGGGVPMASSWKLQYADADGNWQDVKLADGQSYTVNQNEGNEVKFADTV ETDKLRWFPKGAIVGASEFEAYAIEPVSVDEVNRLVQTGSKADDLKLPSTVSAVYTDGSRRDLAVTWDKVTDAQ LAADAVFDVKGIVAGALSGTVAHIAARSDTALQTVGNAQPVEQTVYQNAKSIDLPATVPVKFPNGYNDDRKVTWK DADIKAIDLTKVGDYEVAGTVDDGSSSAAAKLTVHWADPNGSSTPEPEPEPLVGWIEGKATKTTISPDSEATWS PAEGKLNDGVWDDTWPTTDDQNVNDKVWGSWGKAKDGMYAQYDFGQSVTVDQSRAQFWANFAETDDSKGGLEVP DAWKIQYLAEDGSWKDVEPTEDYTIVRNSPASRADTDAKGWSTVTFKPVATKSLRLVLTPHTGSSTFGAAVAEWG VHGIDGTEPEPTPVDKTALESALDTANGLDASRYTAASWAEFQQIIDAAQAVYDDANATAEQVAEQVTKLEDGQK ALVALATDVEKSTLQAAIDAAKAEAASGKYTDKSVEALNKAIEAAEGVLKVGEVGEVTQAAVQEASASLNKAVKA LEEKPAAETVKKESLEASIEQAKKADKSKYTEEAWQALQSQIAAAQKVYDDKDAKQADVDAAQDALDKAFWATKV EQKPGSQQPGVTDTDKDDKDNKGDRVPPTGAAVSWAAAAVLLTAAGVTILKRRQSGDHGSARHSA

[0157] Suitably, the B. longum subsp. iuvenis strain comprises a GH43_17 gene and one or more genes selected from a GH43_22, GH43_27, GH43_29 and GH121 gene as defined herein. Suitably, the B. longum subsp. iuvenis strain comprises a GH43_17, GH43_22, GH43_27, GH43_29 and GH121 gene as defined herein.

[0158] Suitably, one or more of the arabinan-degrading GHs described herein comprises a signal peptide. A ‘signal peptide’ may refer to a short amino acid sequence, typically present at the N-terminus of a polypeptide, which allows the polypeptide to be secreted out of abacterial cell. Without wishing to be bound by theory, this may advantageously allow the present B. longum subsp. iuvenis strain to act as a primary degrader of complex structures of arabinan when present in high molecular weight, usually in the diet. Suitably, a ‘primary degrader’ may refer to a bacterium that is capable of depolymerizing specific polysaccharides to mono-, di-, and oligosaccharides that they can take up and ferment themselves to acidic end products such as acetate or lactate. Suitably, the GH43_22, GH43_27, GH43_29, GH_121, GH43_24 and / or GH30_5 enzyme may comprise a signal peptide. Suitably, each of the GH43_22, GH43_27, GH43_29, GH_121, GH43_24 and GH30_5 enzymes may comprise a signal peptide.

[0159] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family gene that encodes a CAZyme that targets arabinogalactans.

[0160] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 43_24 (GH43_24) gene. Suitably, the GH43_24 gene comprises SEQ ID NO: 19 or a sequence with at least 60% sequence identity to SEQ ID NO: 19. Suitably, the GH43_24 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 19.

[0161] SEQ ID NO: 19 ATGAAGATAAACAATAAGGGCAAGGGCGCTCTTATCGCGGCAATTACCGCCGCGGCAACGCTATTGTCATGCGGG CTGGCCGCTGCAAGTGCCAGTGCGGCAGGTGTGAATTACCTGCCTACCATCGGCCAAGTGCCGACATACACCAAG TTCCAGCCCACAGCCGATCCGGGCAAGAACGCTAGCGATTACTTCCAGCCATATTGGTATGCCAAGAACGCCAAT GATAATGGCGGCACACACATCCAAGCGCACGGTGGCCAAGTGGTCAAGGTTGGCGACGCCTACTACTGGTATGGC GAAGACCGTTCTAACGGTTACGACAACAGCCCCGGTGTTCATGCTTATATGTCGACAGATCTATACAACTGGACC GATCTTGGTGTGGCGCTGCGTGCGGTGACCAGCAAATCTCAGTTGACGGATAAGAGCAATGCCGATTACGCCTAC TTCGACAAGGCCTACAACCTGACCAAGTCCGACGGCAGTGTGGACGCTGCCAAGGCCGACGCAATCTTCCCGTAC CTCAACACCAACCCCGATCAGGATGGTGATGGCGCGGTTGATTCCGTACAGGGCATTTTCGAGCGTCCGAAGATC ATCTACAACAAGAAGAACAAGCAATACGTGCTGTGGTGGCATTCCGATGGAAGCACCACGCCGGGCGGTTCCAAC TATGCACGTGCACTTGCGGGCGTGGCTGTTTCCGACAATCCGGCGGGCCCGTTCACTATGGTGGGTGCCTATCGT TTGCCTAACCAGAACAATTGGAAAGAAGCCGCAGGTAACCCCAGCTGGGGTGAGAACGGTGACAGCCGCGATATG ACTGTGTTCGTGGACCCGAAGGACGACAGTGCCTATGTACTGTATTCTTCCGAAGCCAATGCCACGCTGTACATC GCCAAGCTCAACGATGATTACACCAATGTAGTCAAGACCACGAATGTGGACCAGTCCGAGGGACAAAAGCAGTAC TCTGCTGACGGGCAGTACCCATACATTCTTGCAGACGCTACTACGGATGCCCCGGTGCGTGGCGAAGATTTCCAA ATCGTCAAACAAAATGGTTCGCTGGAAGCTCCTGCCGTATTCCAATATGACGGGCGTTACAACATCATCGCATCT GGTGCAACCGGCTGGGCCCCGAACAAGCAGACCTACTACACCGCCGACTCCATGCTGGGAAGCTGGACCCGTGGC GTGGAAAAGGACGATATCAACGAGAACACGTGGTACAACAACATGCCGGAAGGCGCGGATGGTCTGTTGTCCGTG GGCGATACCCGCGGCACCACATTCGGTTCGCAGTCGGCTAGTGTGCTCGCAGTAGACCAGGAGAAAGGTCACTTC ATCTACCTTGGTGACCGTTGGGATTCCGGTAAAGCCGATTCCACCTATGTTTGGCTGCCGCTGACCATCGGTGAG AACGGCACCATCGAAATGCACAATCCTGCTCAAGAAGGCGAGCCCGACGGTTGGGATCTGAGCTATTGGGGCAAC CATGGTAGCGCCAAGGGCAAGCTGGTCAACTGGACTGTGGAAACCGGCGATGATCTCCCGAAGACCGTGAACACG GGCGGAACCGTTACTCTGCCGGACACCGTCAACGTCAAGGAAGGCGACGATACCATTGCTACCAAGGTGACATGG AATGTGGAAGGCGGTACGGCAGTCAGCAAGTCGACCAAGGCTGCTGGTAACACCTACGCATTCAATGTGCCGGGA ACCTACACCATTACGGGCACTCTTGCCGAGAGCAGTAACTTCAATCCGGGCCGTACATTCCGTAGAACCATCGAT GTTTCCTGCTCCAACCCAATTTCCGGAAGTTGGAAGGAAGCTCATTGGAAGGGCGGCAGCGCGTGCCAGGTTTCT GCGTCCGGCGGTGCTTATGACTTCACGATTACGGACAACGCCAATCGGGGCGTCTGGACGGATCGCAACGAGGGC AGTGCGGTGTACCAGCCTGATGCCCTGGACGTGAACGAAATGCTGGAAACCACGGTCAAGCCGCTCGACTTGGGC GGTAATGGCGATCCGCGCGCCGGTCTGGTGGTCCGTAACGGTCTTACTGGCGCTAACGGCGGCAAGGGATATGCC ACGTTACTTGCCAGCCCAAGCGGCGTTTACATGCAGTACGATTCCAATGCCGATGGCTACATCGATAAGGAAACA TCGCATGTTGGTACCGGCTTCGGCGACCAAGTGCAGCTCAAGCTGGAGCGCACCTCAACCGATACTCTGAAAGGC TACTGGCGTGCTTCCGCGAACGATGAATGGCAGGATGTCGCTACGGTAACGCTGACCGGTGCGGACGTAACCGGG CTCGATGCCGGTGCTTTCGCCACGTCGAACAGCAATGCCGGCGCATTCACCGTGGCCTTCAACGGCACTGCGTTC GGTTCGCAGACTGCTGCTGTGGAGTCCATCGCGGCCAAGGGCCCTGAAGCCACTATCGCCAAGAGGCAGACGCTC GCGCATAAGGACGTGACGGTTACCGCTACGCTCACCAATGGCAAGACGCGTGTACTGGAGCCAGATGAATACACG TTGGAAGGCTTCGACACCACCAAATTGGGCGAGCAAACCGTGACGGTACGCCTTGTCACTGATTCTTCAGTAACT GCCACGCTCACCGTGACTGTGGAAAGCAACCTTGCCCGGTTGTTCTGCTCGTCCGCCGCAGCCTCGAAGTATGAG CCGGCCAGCAGCTGGGCCTCCGCTTCTACGGCCGACCTGACTTGCGACAACAATCTGAGCACCAACTGGTCGAAC TGGGGCACCGGCGACACCTCGCCGTGGCTCAGCTACACCTTCGATAAGGCATATCAGCTGGGCAAGCTCAGCGTT GCGGTGGATAAGGCCAAGGGCGAGGCCGCTCCGAAGAGCTTCACTGTATCGTACCTAGCTGAAGACAACGCCACG TGGACTGATGCCACGCTGCCGGCAGTCACTGTGAATGGTGCTGCTGGAGCCGTGACGGAAGCCGATGTGAGCGCT CTGCCCGCCACCAAGGGCATTCGCCTCAACTTCACCTACGCCGATGGCAATGACTATGCCAAGATCGCTGAAGTA CGCATCGCCGAAGGTGAAGCAACGCCAAAGCCGCAGCCGTCTAGTAACGCCAATCTTGCTGATCTGACTGTGGAT GGCAAGACGGTTGACGGATTCTCCGCGGATATCACCGAATATGCCGGTGCGCTGGCCGGAGACGCTGCTTCTTAC CCGACGGTGGAGGCGACTGCTGCTGACGCGAAGGCTACGGTGCAGGTGGAGCAGGCTTCGACCGAGAACAGCGGC GTGGCCACGGTGACTGTAACTGCTGAGGATGGCACGGCGGAAACCTACACAGTGACATTCGGCGAACTGCCTCAG TTGGCCGAGCTTGCTGTGGAAGTGACCAAGGATTCCTATCAGGTAGGCGATAAGTTCAACGCTGCCGATGTGAAG GTATCCGCCATTTACAAAGTCGGCGATACCGAAACGCTGCGCAAGCTGATTGATCCAACTGATGGTGATCTGAAG TTCACTGGCTTTGATTCTGCCACCGCAGGCACGAAGACCATCACCGTCTCTTATCGTGGCGTGAACGCGACGTTC GAAGTCACGGTCACGGCCACGGAGGTCACTCCCGGCCCTGGAGAGCAGAAGCCCGGCGATACCAACAATCCTGGC AACACTGCTAAGCCCGGTAACACTGCCACGAATAAGCCGGCTGCTAATGGCGCTGCGCCCCTTTCGAATACGGGT GTTGCCGTGGCTGCCATTGCGGTCGTGGTTGTGGTGCTGACAGCTGCGGCTGGTGCCTTGCTCGTCATCCGCAAA CGCCGCGCATAA

[0162] Suitably, the GH43_24 gene may encode a protein shown as SEQ ID NO: 20 or a sequence with at least 80% sequence identity to SEQ ID NO: 20. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 20.

[0163] SEQ ID NO: 20 MKINNKGKGALIAAITAAATLLSCGLAAASASAAGVNYLPTIGQVPTYTKFQPTADPGKNASDYFQPYWYAKNAN DNGGTHIQAHGGQWKVGDAYYWYGEDRSNGYDNSPGVHAYMSTDLYNWTDLGVALRAVTSKSQLTDKSNADYAY FDKAYNLTKSDGSVDAAKADAIFPYLNTNPDQDGDGAVDSVQGIFERPKIIYNKKNKQYVLWWHSDGSTTPGGSN YARALAGVAVSDNPAGPFTMVGAYRLPNQNNWKEAAGNPSWGENGDSRDMTVFVDPKDDSAYVLYSSEANATLYI AKLNDDYTNWKTTNVDQSEGQKQYSADGQYPYILADATTDAPVRGEDFQIVKQNGSLEAPAVFQYDGRYNIIAS GATGWAPNKQTYYTADSMLGSWTRGVEKDDINENTWYNNMPEGADGLLSVGDTRGTTFGSQSASVLAVDQEKGHF IYLGDRWDSGKADSTYVWLPLTIGENGTIEMHNPAQEGEPDGWDLSYWGNHGSAKGKLVNWTVETGDDLPKTVNT GGTVTLPDTVNVKEGDDTIATKVTWNVEGGTAVSKSTKAAGNTYAFNVPGTYTITGTLAESSNFNPGRTFRRTID VSCSNPISGSWKEAHWKGGSACQVSASGGAYDFTITDNANRGVWTDRNEGSAVYQPDALDVNEMLETTVKPLDLG GNGDPRAGLWRNGLTGANGGKGYATLLASPSGVYMQYDSNADGYIDKETSHVGTGFGDQVQLKLERTSTDTLKG YWRASANDEWQDVATVTLTGADVTGLDAGAFATSNSNAGAFTVAFNGTAFGSQTAAVESIAAKGPEATIAKRQTL AHKDVTVTATLTNGKTRVLEPDEYTLEGFDTTKLGEQTVTVRLVTDSSVTATLTVTVESNLARLFCSSAAASKYE PASSWASASTADLTCDNNLSTNWSNWGTGDTSPWLSYTFDKAYQLGKLSVAVDKAKGEAAPKSFTVSYLAEDNAT WTDATLPAVTVNGAAGAVTEADVSALPATKGIRLNFTYADGNDYAKIAEVRIAEGEATPKPQPSSNANLADLTVD GKTVDGFSADITEYAGALAGDAASYPTVEATAADAKATVQVEQASTENSGVATVTVTAEDGTAETYTVTFGELPQ LAELAVEVTKDSYQVGDKFNAADVKVSAIYKVGDTETLRKLIDPTDGDLKFTGFDSATAGTKTITVSYRGVNATF EVTVTATEVTPGPGEQKPGDTNNPGNTAKPGNTATNKPAANGAAPLSNTGVAVAAIAVWWLTAAAGALLVIRK RRA Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 127 (GH127) gene. Suitably, the GH127 gene comprises SEQ ID NO: 21 or a sequence with at least 60% sequence identity to SEQ ID NO: 21. Suitably, the GH127 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 21.

[0164] SEQ ID NO: 21 ATGAACGTTACAATCACTTCCCCGTTCTGGAAGCGGCGTCGCGACCAGATTGTCGAATCCGTCATCCCCTACCAG TGGGGCGTGATGAACGACGAAATCGACACCACAGTGCCCGACGACCCGGCCGGTAACCAGCTGGCTGACAGCAAA AGCCACGCGGTCGCCAATCTGAAGGTTGCCGCCGGCGAATTGGACGACGAATTCCACGGCATGGTGTTCCAGGAT TCCGACGTCTACAAGTGGCTTGAGGAAGCCGCTTATGCGCTGGCCTACCATCCGGATCCCGAACTCAAGGCGCTG TGCGATCGCACGGTCGATCTCATCGCCCGCGCTCAGCAGCCGGACGGCTACTTGGACACTCCGTACCAGATCAAG TCCGGCGTATGGGCCGACCGCCCGCGCTTCAGCCTGATTCAGCAAAGCCACGAGATGTATGTGATGGGTCACTAC ATCGAAGCCGCCGTCGCCTACCATCAGGTGACCGGCAACGAGCAGGCCCTTGAAGTCGCCAAGAAGATGGCCGAC TGCCTGGATGCCAACTTCGGGCCCGAAGAAGGCAAGATTCATGGCGCCGACGGCCACCCGGAAATCGAACTCGCC CTCGCCAAACTGTACGAGGAAACCGGCGAAAAGCGTTACCTGACGCTCTCCCAATACCTCATCGACGTGCGCGGC CAAGACCCTCAGTTCTACACCAAGCAGCTGAAGGCCCTGAACGGCGACAACATCTTCCCCGACCTCGGCTTCTAC AAGCCCACCTACTTCCAGGCCGCCGAACCTGTGCGCGACCAGCAGACCGCGGATGGCCACGCCGTGCGCGTCGGC TACCTGTGCACTGGTGTGGCCCATGTGGGCCGACTGCTCGGCGATCGGGGACTGATCGACACCGCCAAGCGTTTC TGGACGAACATCGTCGCCCGTCGTATGTATGTCACCGGCGCGATTGGTTCCACCCACGTGGGCGAGTCGTTCACC TACGACTATGATCTGCCGAACGACACGATGTACGGTGAGACCTGTGCTTCCGTGGCTATGAGCATGTTCGCCCAG CAGATGCTCGACCTCGAGCCCAAGGGCGAATACGCCGACGTGCTGGAGAAGGAACTGTTCAACGGTTCCATTGCC GGCATCTCGCTCGACGGCAAGCAGTACTACTACGTCAATGCACTGGAGACCACGCCTGACGGACTGGATAACCCG GACCGTCACCACGTGCTCTCCCACCGCGTCGACTGGTTCGGCTGCGCCTGCTGCCCGGCCAACATCGCCCGACTC ATCGCCTCCGTGGACCGCTACATCTACACCGAGCGCGACGGCGGCAAGACCGTGCTGAGCCACCAGTTCATCGCC AACACAGCCGAATTCGCTTCCGGCCTGACGGTCGAGCAGCGTTCGAACTTCCCGTGGGATGGCCATGTGGAATAC ACGGTGAGCCTGCCCGCCAGCGCCACTGACAGCTCGGTCCGTTTCGGACTGCGCATCCCCGGCTGGTCGCGGGGC TCCTACACGCTGACCGTGAACGGCAAGCCCGCAGTGGGTTCGCTGGAAGACGGCTTCGTATACCTTGTGGTCAAC GCCGGCGATACGTTGGAGATTGCGCTCGAGCTCGACATGTCCGTGAAGTTCGTGCGCGCCAACTCCCGCGTGCGC TCCGATGCCGGTCAGGTGGCCGTGATGCGCGGACCGCTGGTCTACTGCGCCGAACAGGTCGATAATCCCGGTGAT TTGTGGAACTATCGTCTGGCCGATGGCGTCACCGGTGCGGATGCCGCTGTGGCTTTCCAGGCCGACTTGCTGGGT GGAGTCGATACCGTTGATTTGCCGGCAGTGCGCGAGCACGCCGACGAGGATGACGCGCCGCTGTACGTGGATGCC GACGAACCGCGTGCGGGTGAGCCCGCGACGCTGCGCTTGGTGCCGTACTACTCGTGGGCCAACCGCGAGATAGGC GAGATGCGTGTCTTCCAGCGTCGATAA

[0165] Suitably, the GH127 gene may encode a protein shown as SEQ ID NO: 22 or a sequence with at least 80% sequence identity to SEQ ID NO: 22. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 22.

[0166] SEQ ID NO: 22 MNVTITSPFWKRRRDQIVESVIPYQWGVMNDEIDTTVPDDPAGNQLADSKSHAVANLKVAAGELDDEFHGMVFQD SDVYKWLEEAAYALAYHPDPELKALCDRTVDLIARAQQPDGYLDTPYQIKSGVWADRPRFSLIQQSHEMYVMGHY IEAAVAYHQVTGNEQALEVAKKMADCLDANFGPEEGKIHGADGHPEIELALAKLYEETGEKRYLTLSQYLIDVRG QDPQFYTKQLKALNGDNIFPDLGFYKPTYFQAAEPVRDQQTADGHAVRVGYLCTGVAHVGRLLGDRGLIDTAKRF WTNIVARRMYVTGAIGSTHVGESFTYDYDLPNDTMYGETCASVAMSMFAQQMLDLEPKGEYADVLEKELFNGSIA GISLDGKQYYYVNALETTPDGLDNPDRHHVLSHRVDWFGCACCPANIARLIASVDRYIYTERDGGKTVLSHQFIA NTAEFASGLTVEQRSNFPWDGHVEYTVSLPASATDSSVRFGLRIPGWSRGSYTLTVNGKPAVGSLEDGFVYLWN AGDTLEIALELDMSVKFVRANSRVRSDAGQVAVMRGPLVYCAEQVDNPGDLWNYRLADGVTGADAAVAFQADLLG GVDTVDLPAVREHADEDDAPLYVDADEPRAGEPATLRLVPYYSWANREIGEMRVFQRR Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 30_5 (GH30_5) gene. Suitably, the GH30_5 gene comprises SEQ ID NO: 23 or a sequence with at least 60% sequence identity to SEQ ID NO: 23. Suitably, the GH30_5 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 23.

[0167] SEQ ID NO: 23 ATGAAGGTACTGAGCAAATCGCTTGCTGCAATGGTTGCGGCGGCAACACTAGTGGGAGGAGGGGCGTTTGCGGTT GCCGGCACTGCGTATGCGGCTGATAACGATGCCATTACCGTGACCCCGAACCCGTGGTATGCCAACAGTTTCGAT GGCTGGGGCACCTCGCTGGCTTGGTTCGCCAACGCCACCGGCAGCCTCGGCGAGGAATCGGCCATCACCACCAAT CTCGGCGATGACGCTTCCAAGGCTAAGGCTGTGGAATACGGCAAACAGCTGCGCGAACAGTTCTACCAGTCCATC TTCGGTGATGAAGGACTGGACCTGAACATGGCCCGCTACAACGTGGGCGGCGGCAATGCCTCCGATGTTGCCTAC GGCTACCCATTCATGCGCCAAGGCGCTGCCGTGCCTGGCACGTGGAAAGATGACGCCACCGGCTCCGGCACGTAT GGCAATGGCGTAACCACCAAGCAGGCCGACAAAGACAAGCTGGCTGCGGCATTCGACCCGACTGACGACAACCAG TATGACTTCTCCAAGTCCGCCGCCCAAGACTGGTGGATTGAGCGCGGTGCCACCGGCGATAACCCTGACATCACC GACGTAGAGGCCTTCGCCAACTCCGCTCCGTGGTTCCTGACCAACAGCGGTTACGCCACTGGTGGACGTAACTCC GGTAGCAATAATCTTGCAAACCCTGAGAAATTCGCTCAGTACATGGCCAAGAACGTCGAGCACCTCGAAAGCCTT GGCGCAAACGTTGACACGGTCGAGCCGTTCAACGAGTCCGAGACCAGTTACTGGGGCACTCCGGGCGACATGGCT TCGAAGTACACCGATGAGAGCGATGACAACACCAAGCTCATTAACAACTACTGGGATAAGTACTACTCCGACAAA GATAAGTCCGTCACCCCATACGCCAACGCGCTGAAGAAGCCGCAGGAGGGTATGCATGTCAGCAACGCCCAGCAG CAGCAGACGATTACCGCACTCGCTGAGGCGCTCAAGGACAATGATGACACCATCATCGCAGCCACCGATGCCACG AACTCCGCCGACTTCGTCAAGTCGTACAACCAGTACCCGCAGGCGATCAAGGACCTTATCGGCCAGTACAACGTT CACGCCTACTCCGACAGCAACCAGATGCAGTCGCGCGATATCGCTCAGGCAGACGGCAAGAAGCTGTCGATGAGC GAGGTGGACGGCTCCTGGCAGTCTGGCTCCTACAACCCGTACGGTTTCGACAACGCGCTGGGCATGATGAGCAAG ATCAGCTCCAACGTCACCCGCCTGCAGTCCAAGGACTTCACCTTCTGGCAGGTGGTCGAGGACCTCTACAACATG CAGATGGGCTCGAATGTGAATCCGGCCGGTGAGAACACCAACTGGGGCACCGTGCTCATCGACTTCGACTGCACC GTGGCTGGCATGGACGGCAAGCTCTACTCCGAGCGCCGCGTGAACAACAACGGCGGTACCACCGATGGACTTGAA CCGTGCACGGTTATTGCAAACGCCAAGTACAACGGCGTCAAGGCCATCACCCACTTCATCCACGCGGGCGACAAG GTCATCGCCAACAACGATGAAGACAACAACATGACTGCCACCTCCGACGATGGCAAGACACAGACCGTCATCCAC CGCAACTCCGGCACCTCTGACCAGACCTTCGTCATCGACCTGTCGAAGTACGGCGAGATTGCCGACAACGCTTAC GGTGAGCTCTACCTGACCACCGAAACCTCTGCCGAAGACAAGAACGCGGGTGTCGATTCCGCCACTCCGGAAGTC TTCGCCAAGACCAGCAACGTCAAGCAAGCTGAAGGCTCTGTGATGATTGACAAGGCTGCCAAGACCGCTACGGTC ACTGTGCCCGCCCGTTCTATCGCCTCCATCCAGCTCACTGGCGTGACCGGCTACGCCAAGGATGCTGCCGTCGAG ACCGGCGACACTTACCAGCTCGTTGGTAAGCAGTCCGGCAAGGCCGTGGCTGATACCACTTCTGGTGATTCCGCG CTGTCCCTGGCCAACGTCGCTTCCGATGCCGAGAACGCCAAGAAGCAGACTTGGACCTTTACCCAGATCGAGCAG CCCGCCGACTCCGAGCGCCCTGATCTCAAGGTTTATGTGATTACTAACGCCGAAGGCAAGGTGCTGGTGTCCAAG GATGGCACGAACGCGCTTTCCAACGAAACGGTTGAGGCCGCTAAGTCCGACCCGGCTGCCAAGTGGATTCTCAAC ACTTCCGATGGTTCGACCTACCAGCTGCTCAATGCCGCGACTAAGACGAACCTCGATGTGGATAACTCTGGTACC ACAGTCGGCACGAAGGTTGGCTTGTGGCAGTCACCGAGCGGCACTTCGCCGTCCGCCAACCAGACATGGACTCTA CGCAATGTAACGCCGACCAGCCAGAAGACCGTGAACGTGCAGACCGCCGTTAACGAGAAGGCCGCGCTGCCGACC GAAGTCACGCTCTACTACACCTGGGGCGAAGGCAAGGCCACGGTTGCCAACTGGGATACTTCCAAGGTCGATGTG GCCAAGGAAGGCACCTACGAAGCCACCGCTACCGCCACCGATGTGTACGGCAACGAGTTCAATGTCGCCGCTACG GTCTACGTTGGCGCGCTCACCGTTTCCGATCCGGTATCGGCTACAGTGCTGGCCGGCACCAGTGCGAGCGAGGCG AAGGCCGCGCTTGAGGCTGCGCCGGTGTATCTGCACGTCAAGGCATCGCCTGCATTCGAGGGCGATGCGGCTAAG GTTACGTGGAACTTCGATGGGCTTGATACCAAGCTCGCCGATGCCAAGGCTGGCGACAACATTGCCGTGACCGGT ACTTACCAGCTGGACGACGCGACCACGATTGCGCTGAAGGGCGCGATCTATGTCACCGCCGCCACGCCTGAGAAT GTGGCCGACACTGCTTCCAGCCTGACCGTGACCAACCAGCAGACGGAATACAGCAAGGGCGATCAGTGGAAGAAG CTCACCGATGGTGACACGTCAGCTGAAGCCTGGGTGACGTGGAACTCTGCTGGTGACTATTCCGCCAGCCCGACC GCCACGATTGACTTCGGCTCTGAGTGTGAGCTTAGCAGCGTGACCATTACGTATGGTGACAAGGCTCCGGCTTCC GCCAAGGCCGAGTACACCACTGATGGCGAGACGTGGATGCAATTCGGTAGCGATGTTAAGCCTGCCGCAGGCCAG ACGGTGACGTTCAAGGCCGATAAGGGCACAGTGAATGCCACGAAGGTGCGCATTGTGAACACCGTGAACAACGAC TACATGAACGCCACCGAAATTCAGGCATTCGTGACGCCGGTTCAGGGTGCTGCGAAGAACATCGCCGCGGCCTCT GGCACGAACTTCTCGGTGAACTTCCAGGAGGGTGCCTCCGCTTCCAAGGCCATCGATGGTGACACTACGTCAAAG GGTTGGTCCACTTGGGCTTCCACCGCCTCGACGGTGGACCCGGTCGCCACGTTCACCTTCGACGAAGCTCAGACC ATCACCGAAGTGAAGACCTTCTTCTACTACGATGGTCGTGCGTCTTGGCCGAAGAGCCAGACGCTGGAATACCAG GATGAGGCTGGCGAATGGCATGGAGTCGGTACCAAGGATGGCTGGAAGATACAGGCCGGCGATGCCGGCTCTGGC TCCGACGGCATCACCGCCGCCGACACCCCGACCGTTGACTTCGTGCTCGGCACCCCGGTAAAGGCCAAGGCCATC CGCCTGACTAACACATTGCAGGACACCAAGGTGTACATCAACGTGGCTGAGATCCAGGTGTTCGCACAAGACAGC ACGGTACTCACCCCGCAGCCAGCATCCGATGCCACGCTGGGCGACCTGCGTCTTGACGGCGAAACCGTTGAAGGC TTCGACCCGGCCAAGACCGACTACACGGTTGATCTGCCGGTCGACGCCGAGGCAAACCCGGTGCTGCAGGCCTTC GCCACCGACAATGCCGCCGCCGTCAAGGTGACTGGCGACGCGGTTGAGAACGGCCAGCTTGGCGGCAAGGCCGCC ATTACGGTGACCTCAGCCGACGAGTCTGAGACGAAGACCTACACGGTGACCTTCAACGCCTTCACTTTGGCTTCG CTCAAGGTGATCGGACCCACGAAGACCGAGTACGCCATCGGCGACAAGCTCGATACCGCCGGTCTGAAGGTGACT GCCGTCTACCAGAGTGGCGACAAGACCAAGGAAGTGCCGGTCGCTCTTGACGACCCGCAGCTTGCGATTGGCTCG TTCGACTCCACCACCGCAGGCAAGAAGGCGATTACCGTCTCCTACCGTGGTGTGACCGCGACCTTCAACGTCACG GTCAAGGCCAACGCAGTCGCCCCTGGCCCTGAAGAACAGAAGCCCGGCAACACCAACAAGCCCGGTGCCACCGGC AGCGGCAACAAGAACACGGTGGCCAACACCGGTTCCAGTGTTGCCGCCATCGCTGGCGCTGTCGCTCTGCTGGCC GCTGCCGCGGGTGCACTGTTCATGCTGCGCAAGCGTGCATAG

[0168] Suitably, the GH30_5 gene may encode a protein shown as SEQ ID NO: 24 or a sequence with at least 80% sequence identity to SEQ ID NO: 24. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 24.

[0169] SEQ ID NO: 24 MKVLSKSLAAMVAAATLVGGGAFAVAGTAYAADNDAITVTPNPWYANSFDGWGTSLAWFANATGSLGEESAITTN LGDDASKAKAVEYGKQLREQFYQSIFGDEGLDLNMARYNVGGGNASDVAYGYPFMRQGAAVPGTWKDDATGSGTY GNGVTTKQADKDKLAAAFDPTDDNQYDFSKSAAQDWWIERGATGDNPDITDVEAFANSAPWFLTNSGYATGGRNS GSNNLANPEKFAQYMAKNVEHLESLGANVDTVEPFNESETSYWGTPGDMASKYTDESDDNTKLINNYWDKYYSDK DKSVTPYANALKKPQEGMHVSNAQQQQTITALAEALKDNDDTIIAATDATNSADFVKSYNQYPQAIKDLIGQYNV HAYSDSNQMQSRDIAQADGKKLSMSEVDGSWQSGSYNPYGFDNALGMMSKISSNVTRLQSKDFTFWQWEDLYNM QMGSNVNPAGENTNWGTVLIDFDCTVAGMDGKLYSERRVNNNGGTTDGLEPCTVIANAKYNGVKAITHFIHAGDK VIANNDEDNNMTATSDDGKTQTVIHRNSGTSDQTFVIDLSKYGEIADNAYGELYLTTETSAEDKNAGVDSATPEV FAKTSNVKQAEGSVMIDKAAKTATVTVPARSIASIQLTGVTGYAKDAAVETGDTYQLVGKQSGKAVADTTSGDSA LSLANVASDAENAKKQTWTFTQIEQPADSERPDLKVYVITNAEGKVLVSKDGTNALSNETVEAAKSDPAAKWILN TSDGSTYQLLNAATKTNLDVDNSGTTVGTKVGLWQSPSGTSPSANQTWTLRNVTPTSQKTVNVQTAVNEKAALPT EVTLYYTWGEGKATVANWDTSKVDVAKEGTYEATATATDVYGNEFNVAATVYVGALTVSDPVSATVLAGTSASEA KAALEAAPVYLHVKASPAFEGDAAKVTWNFDGLDTKLADAKAGDNIAVTGTYQLDDATTIALKGAIYVTAATPEN VADTASSLTVTNQQTEYSKGDQWKKLTDGDTSAEAWVTWNSAGDYSASPTATIDFGSECELSSVTITYGDKAPAS AKAEYTTDGETWMQFGSDVKPAAGQTVTFKADKGTVNATKVRIVNTVNNDYMNATEIQAFVTPVQGAAKNIAAAS GTNFSVNFQEGASASKAIDGDTTSKGWSTWASTASTVDPVATFTFDEAQTITEVKTFFYYDGRASWPKSQTLEYQ DEAGEWHGVGTKDGWKIQAGDAGSGSDGITAADTPTVDFVLGTPVKAKAIRLTNTLQDTKVYINVAEIQVFAQDS TVLTPQPASDATLGDLRLDGETVEGFDPAKTDYTVDLPVDAEANPVLQAFATDNAAAVKVTGDAVENGQLGGKAA ITVTSADESETKTYTVTFNAFTLASLKVIGPTKTEYAIGDKLDTAGLKVTAVYQSGDKTKEVPVALDDPQLAIGS FDSTTAGKKAITVSYRGVTATFNVTVKANAVAPGPEEQKPGNTNKPGATGSGNKNTVANTGSSVAAIAGAVALLA AAAGALFMLRKRA

[0170] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 43_32 (GH42_32) gene. Suitably, the GH42_32 gene comprises SEQ ID NO: 25 or a sequence with at least 60% sequence identity to SEQ ID NO: 25. Suitably, the GH42_32 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 25.

[0171] SEQ ID NO: 25 ATGACCGCAACCATCAGCAACGGTGTATCCGCCAGCTACAGCCCTGCGGAAGACGAGCTCGGCGCAGCTGACCCC ACCGCCTTGCTTGCCGAATCTGGCGATTTGAAGCCGCTGGCCGAACGCACTTATACGAATCCGGTTCCATATGCG GACGGTAAGTCCCATACCGCGCCCGACCCGTTCGTGCTCAAATACCGCGACCTCTACTACTGCTATGCCACCGAC GAGCACGGCATTCTGGTCTCCACCTCACCGGACATGGTGCACTGGACCTCACATGGATTCTGCTACACCGAAGCC GGACGCAGAAACTTCTGGGCCCCATCGGTGATTCTCATCAACGGCGTCTTTCACATGTACTTCTCGAATATGCCG GCCGAGGAGACCGACACCCACACGGAAATCATGCGTGTGGCCGTGAGCGAGGATCCGCTCGGCCCGTTCGAAAAG AAAGCGGAGCTGTTCAACACCTTCGCCATCGACTCCCAAGTGGTCTATGGCGATGACGGCCAGTTGTACTTGCTT TACGCCGACAATCAGGTCACCGGCCTGAGCGATGACCGGCCCGGAACCTCCGTGATGATCGATCGCCTTGTGACC CCGTATTCGCGTGAGAACAAACCGCGCCCGCTCATCGTGCCCACCATGGACGAGGAGATCTTTGCCCGCAACCGT TTCGGCGATGGCCGCGACTGGCACACCGTAGAAGGCGCCACATACTTCGCCTACCGTGACCGCGCGTTCATCACC TACTCGGCCAACGCCTACGAGCATGAGGACTACTTCGTCGGATACTCGTACGCACAGCTGCCGAATAAGCAGGCC GACGCCCACATCGATCAGCTCGATTGGACGAAACAGCTCAACGAGAACCGCTTCGATCCGCTGCTTATCCGCAGC CCAAAGGTTGAAGGCACGGGCCACAACTCCATAGTCAAAGCGCCCAATGCCGTTGATGACTGGATTGTCTACCAC GGCCGTAACGCCGATGACGAGCTGTATGTGGGCACCGAACAGCGCGTAATGCGCATCGACCCGCTGTACTACGCC GAAGGAGGGCTCGACACCCCAGGACCTACCGCCGCCGCTCAAAGCGCACCGCTGTATGGCACTGTGCATGATGAT TTTGCGGATGGCCTGAACGCCGGATGGTCGGTTATTTCCGGTGCGGCCCACACCGAATCCGATGTGGACGGTCAC GCGCTTGTTGCCGACGAATCCAGTGTATTCATCGCTGTGTCGGGCAAATCGTCCGCAACCCAAGTGATTGACGTC TGGGCCAAAGCTCCCGTCACCCCACTGGGCGCACGATTCGGTATCGTGGTGCGGTACCAGGATGCCAACAACCTC ACCAAACTCGAGGTGGATGCTGGCCGTCAGGTAATTAGCGTGGTCGATGTGATCGGCGGCGTTGCCTCCGAACGC GTGACCAATGCCGACCTCCATGACTTCGATTCCCATGCCTGGCATGAGTACCGGCTTGAGCGCCGCTACTGCAGG CTGGAGATCCGCATTGATGGCCGTTTCGCCGCGTCCTGCACCATCAGTGATAAGCCCGGTCGGGCGGGATTGTTC TCGTTGCGAACGGGGGCCGCGTTCAGCGCATATGCGGCCACTGAACATGTGAATCTGTGGGGTGCCGGATTGCGG GATCTCGGTCGAGAATTGCATGCTGACCGCCGACTCGTCATCGACGGCGGCGTGAGGTCCAGCGGCGTGTGTCCG GTAACACTCGAACTGGCATACCCGCTGGTCAGCAACCGTTTCGTCCTTGATTTCGCTGGGCAGACGAGCCGTGGG CAGGCGCTGTTGTCTCTTGGCGAATACCGTTTGTCCGGCACGGCATCATCCGTGGAGTTCATGCGCAACGGCAAG TCTCTGCCTTCCACCCCGGAGCCGGCCAGGCTGCGTGTCTTTGAAGACAACGTCCGCCGTGACCGTTCGGGCCGA GCCGTGCTCACCATCCGTATCGAAGCTCTGAACGGCACGATGCGACTGCACCTACGTGGCAAAACCTGGCAGGTG CCGTTTGCGGACAATGCGGCCCGTGCCCGTATCACTCTTGATCGCGCATCCCTGACCGGATACGAGAGGACATCG CTGGAATCCAGCATCGAGGAAAGGAGTGCGTCCGGCAATTGA

[0172] Suitably, the GH42_32 gene may encode a protein shown as SEQ ID NO: 26 or a sequence with at least 80% sequence identity to SEQ ID NO: 26. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 26.

[0173] SEQ ID NO: 26 MTATISNGVSASYSPAEDELGAADPTALLAESGDLKPLAERTYTNPVPYADGKSHTAPDPFVLKYRDLYYCYATD EHGILVSTSPDMVHWTSHGFCYTEAGRRNFWAPSVILINGVFHMYFSNMPAEETDTHTEIMRVAVSEDPLGPFEK KAELFNTFAIDSQWYGDDGQLYLLYADNQVTGLSDDRPGTSVMIDRLVTPYSRENKPRPLIVPTMDEEIFARNR FGDGRDWHTVEGATYFAYRDRAFITYSANAYEHEDYFVGYSYAQLPNKQADAHIDQLDWTKQLNENRFDPLLIRS PKVEGTGHNSIVKAPNAVDDWIVYHGRNADDELYVGTEQRVMRIDPLYYAEGGLDTPGPTAAAQSAPLYGTVHDD FADGLNAGWSVISGAAHTESDVDGHALVADESSVFIAVSGKSSATQVIDVWAKAPVTPLGARFGIWRYQDANNL TKLEVDAGRQVISWDVIGGVASERVTNADLHDFDSHAWHEYRLERRYCRLEIRIDGRFAASCTISDKPGRAGLF SLRTGAAFSAYAATEHVNLWGAGLRDLGRELHADRRLVIDGGVRSSGVCPVTLELAYPLVSNRFVLDFAGQTSRG QALLSLGEYRLSGTASSVEFMRNGKSLPSTPEPARLRVFEDNVRRDRSGRAVLTIRIEALNGTMRLHLRGKTWQV PFADNAARARITLDRASLTGYERTSLESSIEERSASGN

[0174] Suitably, the B. longum subsp. iuvenis strain comprises one or more genes selected from a GH43_24, GH127, GH30_5, and GH 43_32 gene as defined herein.

[0175] Suitably, the B. longum subsp. iuvenis strain comprises a GH43_17 gene and one or more selected from a GH43_24, GH127, GH30_5, and GH 43_32 gene as defined herein.

[0176] Suitably, the B. longum subsp. iuvenis strain comprises a GH43_17, GH43_24, GH127, GH30_5, and GH 43_32 gene as defined herein.

[0177] Suitably, the B. longum subsp. iuvenis strain comprises a GH43_17, GH43_22, GH43_27, GH43_29, GH121, GH43_24, GH127, GH30_5, and GH 43_32 gene as defined herein. Suitably, the B. longum subsp. iuvenis strain comprises a GH43_17, GH43_22, GH43_27, GH43_29, GH121, GH43_24, GH127, GH30_5, GH 43_32, as defined herein.

[0178] GH43 17 gene cluster

[0179] Suitably, the B. longum subsp. iuvenis strain may comprise one or more genes encoding for a family 31 glucosidase (GH31), an ABC transporter, a Lac-I type regulator, a MFS transporter and / or an AraC family transcriptional regulator.

[0180] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 31 (GH31) gene. Suitably, the GH31 gene comprises SEQ ID NO: 27 or a sequence with at least 60% sequence identity to SEQ ID NO: 27. Suitably, the GH31 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 27.

[0181] SEQ ID NO: 27 ATGACAACTTCATTCACCATCGACGGCAACGCCCTGATCTGGACCGGGGACGGCGAAACCCTGCGCATCGAACCT TGGGAAGAGAACAGCGTACGTGTACGCGCCACCCGCAACCGTGGCTTCGGCCCGGTCGATTGGGCGCTTCTGGAA CCGAAGAATGAATCCGGCCGTGTCGCAGACATCGCCGTCGGCGAGGACGGCGAACACGCCAGCCTGACCAACGGC AGCATCACCGTTAAAGCGGATTCGAATCATGCTCCATTGCTGTCTGCCGGATATGAAACCTTCCGGTGTGACCTG AGCTTCTGGAACGCCGAAGGCGAACTCCTGTTCCGCGAATATCCACAAGGTGGGTCGCTTTTGCTCAAGGCGCGT GACTACACTCCGGTGTCCGGTGAAAGCTTCGCCGTGACCACGTCTTTCAGCGCCGATCCCAAAGAACGGCTGTAT GGCATGGGCGAATACCAACAGGACGTGCTTGACCTCAAAGGCTCCACCTTTGAACTTGCGCACCGTAATTCCCAA GCCTCCGTGCCGTTCGTCGTCTCCTCCAAGGGGTACGGCTTCCTGTGGCACAATCCGGCTATTGGCCGCGCCACT TTTGGACGCAACCGAACCGAATGGGCGGCTCAGTCCACTGACCAGATTGACTACTGGGTCACCGCCGGTGACTCC TACGCGCAGATCGAATCGCAATATGCCGACGCCACCGGACATGCGCCAGTCATGCCTGAATGGGGTATGGGCTTC TGGCAGTGCAAGCTGCGTTACTGGAACCAGGAACAATTGCTTGACGTGGCCCGAGGCTTCAAATCCCGGAACATC CCGCTAGACCTCATCGTCATTGACTTCTTTCACTGGCCTCATTTGGGCGACTATAAGTTCGAGGACGAATTCTGG CCTGATCCCGAGGCCATGGTCGCCGAGCTCAACAGCATGGGCGTCAAGCTCATGGTGTCTGTGTGGCCGCAGGTC TCGGTCTCATCCGAGAACTTCGTGGAGATGAAGCGCAACAACTATCTGGTAAGCGCTGAAGCTGGGCTCAATCTT GACATGATGTTCGAAGAGCCGTGCGTCAACTATGATCCCACCAACCCGGGAGCTCGCAAATTTGTGTGGGACAAG TGCAAGGCCAACTATTGGGACAAGGGCGTGCGCGCCTTCTGGCTGGATGAGGCCGAACCCGAATATGGTGTCTAC GATTTTCGCAACTACCGCTACCACATGGGCAGCGACCTCAACGTGGGTAACGTCTATCCGCAGGCTTACAACCGC GGATTCTACGAGGGGCAGATAGAAGCCGGCATGGAAGGCGAGATCGTTAACCTGACTCGATGTGCGTGGGCTGGA TCTCAACGTTACGGATCGTTGGTCTGGTCTGGAGACGTTGGCTCCACATTCGCCGATCTGAAATCGCAGATTACC TGTGCTATTCACATGGGTATGGCTGGCATCCCTTGGTTCACTACAGACATGGGCGGCTTCCATGATGGGGTGATC GATTCGGATTCATTCAAGGAGCTGCTGGCCCGCTGGTGCGCGTTCTCCTGCTTCCTGCCCGTCATGCGCAACCAT GGTGACCGCAGCCTGGGGGAGTCGACCGGCAAGCAAACCATCACCAAGGCAACCGGTGAGCACCGTTCGCCTTCG GGCGCGGACAACGAGCCATGGAGCTATGGCCCTGAAATGGAGTCCATATTCCGTAAATACATCGCCGTGCGCGAG GTCATGCGCCCGTATACCCGTGAACTGTTCCAGTCTGCCCATGAGCAGGGTCAGCCGTTGGTGCGAGGACTGTTC TACGAGTTTCCGACCGATGAACACGTGGCCGACATTGCGGACGAATACCTGTACGGTCCTGACATTCTTGTGGCT CCCGTAGTCGAGGCCGGTGCTGCTTCCCGTAGCGTCTACCTTCCTGGCGATGAGACGACCACTTGGACTGATTTG CGAGACGGTGCCGTATACGCGGGTGGGCAGAGCATCGAGTCGTCTGCAGCAATCGACACGGTCCCTGCCTTTGCG CGAGATGGTCGGGACCATGGTTTGATTGGTCTGTTGTAG

[0182] Suitably, the GH31 gene may encode a protein shown as SEQ ID NO: 28 or a sequence with at least 80% sequence identity to SEQ ID NO: 28. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 28.

[0183] SEQ ID NO: 28 MTTSFTIDGNALIWTGDGETLRIEPWEENSVRVRATRNRGFGPVDWALLEPKNESGRVADIAVGEDGEHASLTNG SITVKADSNHAPLLSAGYETFRCDLSFWNAEGELLFREYPQGGSLLLKARDYTPVSGESFAVTTSFSADPKERLY GMGEYQQDVLDLKGSTFELAHRNSQASVPFWSSKGYGFLWHNPAIGRATFGRNRTEWAAQSTDQIDYWVTAGDS YAQIESQYADATGHAPVMPEWGMGFWQCKLRYWNQEQLLDVARGFKSRNIPLDLIVIDFFHWPHLGDYKFEDEFW PDPEAMVAELNSMGVKLMVSVWPQVSVSSENFVEMKRNNYLVSAEAGLNLDMMFEEPCVNYDPTNPGARKFVWDK CKANYWDKGVRAFWLDEAEPEYGVYDFRNYRYHMGSDLNVGNVYPQAYNRGFYEGQIEAGMEGEIVNLTRCAWAG SQRYGSLVWSGDVGSTFADLKSQITCAIHMGMAGIPWFTTDMGGFHDGVIDSDSFKELLARWCAFSCFLPVMRNH GDRSLGESTGKQTITKATGEHRSPSGADNEPWSYGPEMESIFRKYIAVREVMRPYTRELFQSAHEQGQPLVRGLF YEFPTDEHVADIADEYLYGPDILVAPWEAGAASRSVYLPGDETTTWTDLRDGAVYAGGQSIESSAAIDTVPAFA RDGRDHGLIGLL

[0184] Suitably, the present B. longum subsp. iuvenis strain comprises one or more ABC transporter genes. Suitably, the ABC transporter genes comprise SEQ ID NO: 29-31 or sequences with at least 60% sequence identity to SEQ ID NO: 29-31. Suitably, the ABC transporter gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 29-31. Suitably, the present B. longum subsp. iuvenis strain comprises a gene with at least 60% sequence identity to SEQ ID NO: 29, a gene with at least 60% sequence identity to SEQ ID NO: 30 and a gene with at least 60% sequence identity to SEQ ID NO: 31.

[0185] SEQ ID NO: 29 ATGACGCATCGTAGCACCTGGTGGAAAACCGCTCTCGGCATCATATTGACGCTCATCATGATGTTTCCTGTCTAC TGGATGATCAACATCTCGTTCACTGGTAAGGCATCCATTCGTTCCGGCGACCTGTGGCCCAAGGATTTCACCTTT GACAACTACGCCCGCGTAATCGCCGACCAAATGCCCTATCTGGGCACTTCCATCCTCGTAGCGGTATGCTGCGTG ATTCTAACGCTGGTCATCGCACTGCCTGCCGCCTACGCACTGGCTTTGCTGCGCTGTCCAGGCAGCGGCGCGCTC AGCTTCCTGCTCATCGTGGCTCAGATGATTCCCGCCGTCGTGATGTCGCTCGGCTTCTACGAGATTTATAACAAC ATTGGTCTGCTCGATACGTTGCCCGGCCTGATCCTCGCCGACTCGACCATTGCGGTGCCGTTCGCGGTCATGCTC CTGACTTCTTTCATGGCCGGCATCCCGCGGTCCCTGCTTGAGGCCGCCGAAGTGGATGGAGCCTCACGTACCCGT CGCTTCTTTTCCATTGTCATCCCGTTATCGCGCAATTCGATCGTGACCGTCTCCCTGTTCGCTTTCCTATGGTCT TGGAGCGACTTCCTGTTCGCTTCCACCCTTGACTCCGGCGGCGGCAAGATGCGCCCGATCACTATGGGTCTGTAC AACTATATCGGTGCGCAGACCCAGGAATGGGGGCCGATGATGGCCACCGCAGTGCTTGCATCCATTCCCGCGACC ATCCTGCTTGTCTTCGCCCAGAAGTACGTCGCCGCAGGCGTGACCGCCGGTGCTGTTAAGGACTAA SEQ ID NO: 30 ATGACAGCCTCAACAACAAGCCCCGTTCGCCGGGCAAAGTCCGGCACTCCGGTCCGGGCCAAACTGGCCATCGCC GGATTCATTGCCCCACTGATTATCTACTTGGTAATCTTTTACGCGTTCCCGCTCATCCAGAACGTGTCAATGAGC CTGCACCGATACACGCGACGAACCTTCGTTACCGGAGATGCGCTGTTCGTGGGTCTCGACATCTACAAGGAAGTC ATTTCCTCCGTGGAGTTCTGGCCGGTTGTGGGGCAGACCTTCGTGTTCGTGGTCGTCTCGCTGATATTCCAATAT GTAATCGGCTTGGCCCTGGCGGTGTTCTTCAACGATAACTTCAAGCTCTCTGGTGTGCTGCGCGGCATCATGCTG GTTCCGTGGCTGTTGCCGCTGATTGTTTCTGGAACCGTCTGGCAGTGGATGATGGACCCTGACTCCGGCATCCTC AACATGTTCCTCGGTCTGTTTGACATCGAACCCATCTGGTGGCTCCAGGCGGATAACTCGCTGTGGGCCGTCATC ATCGCCAACATCTGGCTGGGAATCCCCTTCAACCTCGTGATCCTGTATTCCGGCCTACAGAACATCAGCGGCGAC CTGTATGAAGCCGCCTCCCTCGATGGCTGCAACGCCTGGCAGCGCTTCTGGAAGATCACCTTCCCTCTCCTGAAG CCCGTCACTTCGATCACCCTGTTGCTCGGCTTCGTCTATACATTGAAGGTCGTTGACGTGATCTGGATGATGTCC CAGGGAACCGGCACCTCGCGTACCCTCGCCACCTGGGCCTATTCGATGGCATTTGGCAAGGGAACTTCAATGACT ATCAAATACTCGGAGGCTTCGGTGCTCGGCACGATTCTCATCATCGTGGCGTTGATTTTCGGACTGATTTACCTG CGGGTCCAGAAGACCCAGGAAACCTGCTAA SEQ ID NO: 31 ATGAAGTCCAATACCGCTCTTAAGATAACCGCCGCATTATGCTCCTGCGCCATGCTTGTCGGCGTCAGCGCCTGT GGTTCGAGCAACAGCACCACGGATGATAAGGTGATCGAATGGTGGGATGACTGGACCCGCCACGAGGATGGCTCC GAGTTCGACAAACTGGTCAAGGCGTGTGCGCCCGAAGGCTACACAATTGAGCGCCAAGCCATCGCCACTTCCGAC CTGCTCAACAACCTCACCACCGCAATCAAGGAAGACAATGGCCCGGATGTTGCGGTCATCGACAACCCGATGATT CCGTCCGCCGTCGATGCGGGTTTGGTTGCTGGTTCCGACGAAACTGGTCTTGACGTTTCTGCCTGGGATGAGAAC CTTGAGGCTCCGGGCGTAGTGGACGGCCAGGCATATGGCGTGCCGCTGGGCGGATCCAACACGTTGGGTCTTATG TACAACCCCACCATCATTGAGGCAGCCGGTGTGGATGTATCCACCATCACCGATTGGGATTCGCTCAACGCGGCC ATCAAGAAGGTCGTTGACGCCGGATACAAGGGCATTACGTTCTCGGGCATCTCGGGTGAGGAAGGCGTCTTCCAG TTCCTGCCTTGGTTCTGGGGCGCAGGTGGTGATCTGTCCAAGCTTGACTCCCAGGCGCAGAAGGACGCCGAAGAC CTGCTTTCCGGGTGGATCAGCAAGGGATGGGCTCCCAAGTCCGCCACGACCAACACCCAGTCGGCCTCCTGGGAT CTGTTCCTGGCTGGCGACTACGGATTTGCTGAAATCGGCACCTGGATGCAGTCCGAGGCAGACGAGGCCGGAGCC AAACTTATTCCGATCCCCGCAAAGGATGGCGGCGTGGCCACCGTGCCGACCGGTGGCGAGTTCGCCATGGTCGCC TACCACAAGAAGGATGCGGAATCCCACTACAAGCTCGCCAATCAGGTTATCGAATGTCTTTCCGAGGACGAGACT CTGCTTAAGGTAAGCAACGCTCTGAGCAACCTCGCTGCCAAGAAGGCCGTGCGTGCCGAGCAGCTCGCGGCTAGC GACGGCTTGGCTCAGTGGAAGGAATCCATCGAGAACGCCGCCGGCCGTACCTCCGACTTGGGTCTCAAATACGAG GAAGCCTCCGCAAGCATCTCCGAATCCCTGCTGGCGGCCCTTAACGCGGCTTGA

[0186] Suitably, the ABC transporter genes may encode a proteins shown as SEQ ID NO: 32-34 or polypeptide with at least 80% sequence identity to SEQ ID NO: 32-34. Suitably, the gene may encode a polypeptide with at least 80%, at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 32. Suitably, the gene may encode a polypeptide with at least 80%, at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 33. Suitably, the gene may encode a polypeptide with at least 80%, at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 34.

[0187] SEQ ID NO: 32 MTHRSTWWKTALGIILTLIMMFPVYWMINISFTGKASIRSGDLWPKDFTFDNYARVIADQMPYLGTSILVAVCCV ILTLVIALPAAYALALLRCPGSGALSFLLIVAQMIPAWMSLGFYEIYNNIGLLDTLPGLILADSTIAVPFAVML LTSFMAGIPRSLLEAAEVDGASRTRRFFSIVIPLSRNSIVTVSLFAFLWSWSDFLFASTLDSGGGKMRPITMGLY NYI GAQTQEWGPMMATAVLAS I PAT I LLVFAQKYVAAGVTAGAVKD SEQ ID NO: 33

[0188] MTASTTSPVRRAKSGTPVRAKLAIAGFIAPLIIYLVI FYAFPLIQNVSMSLHRYTRRTFVTGDALFVGLDI YKEV ISSVEFWPWGQTFVFVWSLIFQYVIGLALAVFFNDNFKLSGVLRGIMLVPWLLPLIVSGTVWQWMMDPDSGIL NMFLGLFDIEPIWWLQADNSLWAVIIANIWLGIPFNLVILYSGLQNISGDLYEAASLDGCNAWQRFWKITFPLLK PVTSITLLLGFVYTLKWDVIWMMSQGTGTSRTLATWAYSMAFGKGTSMTIKYSEASVLGTILIIVALIFGLIYL RVQKTQETC SEQ ID NO: 34 MKSNTALKITAALCSCAMLVGVSACGSSNSTTDDKVIEWWDDWTRHEDGSEFDKLVKACAPEGYTIERQAIATSD LLNNLTTAIKEDNGPDVAVIDNPMIPSAVDAGLVAGSDETGLDVSAWDENLEAPGWDGQAYGVPLGGSNTLGLM YNPTIIEAAGVDVSTITDWDSLNAAIKKWDAGYKGITFSGISGEEGVFQFLPWFWGAGGDLSKLDSQAQKDAED LLSGWISKGWAPKSATTNTQSASWDLFLAGDYGFAEIGTWMQSEADEAGAKLIPIPAKDGGVATVPTGGEFAMVA YHKKDAESHYKLANQVIECLSEDETLLKVSNALSNLAAKKAVRAEQLAASDGLAQWKESIENAAGRTSDLGLKYE EASASISESL LAALNAA

[0189] Suitably, the present B. longum subsp. iuvenis strain comprises a Lac-I type regulator gene. Suitably, the Lac-I type regulator gene comprises SEQ ID NO: 35 or a sequence with at least 60% sequence identity to SEQ ID NO: 35. Suitably, the Lac-I type regulator gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 35.

[0190] SEQ ID NO: 35 ATGGTGACCATCAACGACGTGGCGCGGGAGGCAGGAGTCTCCAAAACCACGGTCTCATTCGTGCTTTCGGGCTCG CGCCCCGTTGCTGCAGCCACCGAACAACGTATCCGTGAGGCAATGGACAGACTCGGCTATACCGTCAATCATGCC GCCCGCAGCTTGTCCACTTCGAAGACCATGACCATAGCCGTGGTGACCAGCAACCGGCAGGACGCCTACTTTGAC ATTGCCCGTGGCACATACATCAACGGCTTATCCCGAGCAGCCGCCGAAACCGGCTACGACATGCTCATCACTAAC GATCCAGACGGCTCCGCTACGGAGAACGCCTGCCAATCACACAAGGCGGATGGGCTGGTTTTTTTAGACGTCAGG CAGAACGATCCGCGTGTGCCGATTGCCGCTGAATCCGGCATTCCAACAGTCTCGCTAGGAGTCCCAGTCAATCCA ATGAATCTTGATGTGGTCGACACCGACTTCACGGACATGGCGGCCTCGACCATGCGTACACTGCACGATGCCGGA CACCGCCGCGTCAGCGTCATCACGCTCAGTAGCCGGGTGATTGCCGAACAACTCAACGACACCGCTCGATTCCTC AGGGAAATCGAACGTTCCGGAGAACGACTTGGCATGCATGCCACTATCCGACATTGCTCTACAAGGCCCGGAATC ATCGACACAGACATCGCTCGCATTCTTGACGGTCGAGGTGAGGACACCGCATTCGTCATCCATAATGAATCGGCC GTATTGGTGTTCAGACGGGCAGTGGAACATCGCGGACTGCGCATCCCCGAGGATATCTCCGTCATCGCCATCAAT GAAAAGCAGATGTCGGACGCTCTGTATCTGCCATATTCCGCCTACGAAAACGACGTGGAACTGGTCACCCAATCT GCCGTCAATACGCTTGTGGACCGTATCGAACATCCCGAGCTGACGCCGACACGAACGTTGATCAAGGCCTCGTAC ATAGATCGAGACTCCGTGGCCAATATCTGA

[0191] Suitably, the Lac-I type regulator gene may encode a protein shown as SEQ ID NO: 36 or a sequence with at least 80% sequence identity to SEQ ID NO: 36. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 36.

[0192] SEQ ID NO: 36 MVTINDVAREAGVSKTTVSFVLSGSRPVAAATEQRIREAMDRLGYTVNHAARSLSTSKTMTIAVVTSN RQDAYFDIARGTYINGLSRAAAETGYDMLITNDPDGSATENACQSHKADGLVFLDVRQNDPRVPIAAE SGIPTVSLGVPVNPMNLDVVDTDFTDMAASTMRTLHDAGHRRVSVITLSSRVIAEQLNDTARFLREIE RSGERLGMHATIRHCSTRPGIIDTDIARILDGRGEDTAFVIHNESAVLVFRRAVEHRGLRIPEDISVI AINEKQMSDALYLPYSAYENDVELVTQSAVNTLVDRIEHPELTPTRTLIKASYIDRDSVANI

[0193] Suitably, the present B. longum subsp. iuvenis strain comprises a facilitator superfamily (MFS) gene. Suitably, the MFS gene comprises SEQ ID NO: 37 or a sequence with at least 60% sequence identity to SEQ ID NO: 37. Suitably, the MFS gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 37.

[0194] SEQ ID NO: 37 ATCGCCGAGTTCCATTACGCTATCGGGCATTTTCATTGTGCCGGTCATCGGATTGGTTGCTCAGGCATTCCCGGA CAGCTCGCTCTCCAGCGTGCAGATGATTGTTTCGGCATCACTCTGACCGCACTGGTTGGCGCTTGGCTGACCGGC AAACTCGCCAGCATTCTATCCCGGAAGACCGTGGCACTGATTGGTGCAGGCGGCATGCTGCTGTTCGGTCTGCTG CCGTACTTCGTGCATTCCAGTCTGGCTGCAGTCATCGCGTTTTCCGCGTTGATGGGCGTATGCCTAGGCTTTATC AACAACGTGCTGCCTACTTTGATCTCCGTGCACTACGAGGGCGATGAGCGACAGTCGATTATGGGTCAGCAGGTT GCCGTGGCCAGCATCGGTGCGATGGTGTTCATGACCGTGGCCGGCAAACTCGCCACCGCACAGTGGTATCACGCC TACCTCATCTACTTGTTCGCCGCCGTGGTGCTGGTGGTCTGCGCATTCACGCTGCCCACCAAGAATGGTGAGACG GACGAAGCCGGCCGGATTCAGGGAACGGGGCCTTCCGCGTCGATTCGCGAGGTTATGACCGGCAAACTGTGGTTC TTGGTTGTTGCCGGCTTCTTCTTCCTTCTGGCGAACAATGCCTACAGCAACAACTTGTCCCTGTTGGTCGAGCAG CGCGGCTTGGGCGATGCCGGAACCGCTGGACTGATTTCCACCATCGGACAGTTCGGCGGACTGCTGGCTGGTTTG TGCGTCGGTCTTATGGTCCGATTCGTGAAGAACCATTTGCTGATGGTCGGCTTCATTGTCGAGGGCCTGTCTTTG CTGCTGCTTGGCTGCTCGGCCAGCCTGCCACTGCTCATCATCGGCAGTTTCTTTGCCGGAGCCGGCCTGAGCATC TACTATGCGCAGGCGCCATTCCTCGTCACCGTCATCGAAAAGCCCTACCTCATCCCGCTGGGCATTGCTGCCATG ACCACGGCCAACGCACTGGGCGGATTTGCCAGCCCTGTGCTCGTCAACGCGATTAACGGACTGTTTGGTTCGCAC GCGGCCGGCGCGATGTTCATCGGTGCCGCGATTGCTCTGGCCGGAGCGGTGGCTCTCGGTGTGAGCGGATTCCAA AAGAAGTGCCTCGAAAGCGCGAAGTGA

[0195] Suitably, the MFS gene may encode a protein shown as SEQ ID NO: 38 or a sequence with at least 80% sequence identity to SEQ ID NO: 38. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 38.

[0196] SEQ ID NO: 38 MAEFHYAIGHFHCAGHRIGCSGIPGQLALQRADDCFGITLTALVGAWLTGKLASILSRKTVALIGAGGMLLFGLL PYFVHSSLAAVIAFSALMGVCLGFINNVLPTLISVHYEGDERQSIMGQQVAVASIGAMVFMTVAGKLATAQWYHA YLIYLFAAWLWCAFTLPTKNGETDEAGRIQGTGPSASIREVMTGKLWFLWAGFFFLLANNAYSNNLSLLVEQ RGLGDAGTAGLISTIGQFGGLLAGLCVGLMVRFVKNHLLMVGFIVEGLSLLLLGCSASLPLLIIGSFFAGAGLSI YYAQAPFLVTVIEKPYLIPLGIAAMTTANALGGFASPVLVNAINGLFGSHAAGAMFIGAAIALAGAVALGVSGFQ KKCLESAK

[0197] Suitably, the present B. longum subsp. iuvenis strain comprises an AraC family transcriptional regulator gene. Suitably, the AraC gene comprises SEQ ID NO: 39 ora sequence with at least 60% sequence identity to SEQ ID NO: 39. Suitably, the AraC gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 39.

[0198] SEQ ID NO: 39 ATGGAGCGCGATGCTTTCCGGCTGCCGGGCCTCACCGCCGGCGATGACAACCAGTATGCCGATCACACGCTCACC GGCATGGCAGCCGATGCGGCGAACGTCATAGCCGCAGGCGGTCCCGCCCCGCTGACTAGCTTCGGCACTGTCGCT CAAGCCGCCCATCTCAATCCAGATGACGGCTTCGGCATCATTGGCCATGATCTTGCACACCCATCGCACCTACAC CGGCATGACTATATGGAAATCACGCACGCCATCGCCGGTACGGTACTGGTCTGGGTCGAAGGAGAGACCAACGTG CTGACACAGGGCGGCACCATACTCATCAAGCCTGGAGCCCGTCATCTCATCTCCCCCATCATCGAATACGGGCAA ACACCACACGAGGCGGACATCCTGATTAAACCCGAGCTCATCAGGCAATGCCGCATTCCGATTCTGGAAGCAGCC GGCGCCGACCGGATGTTCATTAGCTGGCTTGACGATGACCGGCAGACCCACTGCCTGCTGGCAGCCGGCAAGCAC CACGCCGGCGAGGCCGCTATCAGCCGCATGTTCATCGCCTACTGCATCAACGCAACCTACAGGCCAGACTTCACC GTCATCGGCAACCTGCTCGAGCTGTTCCACGAAACGTCCCGAGTCTTGGAACACCAGCCACGTACCGATCCGCTG ATCGCCGCCATCATCGAAACCATCACGGCAGATCCCGCCACGGCCCACAACCAGGCCATAGCGGACACACTTGGA TACAGCGTGGGATATCTGTCCCGGTACGCGCGCAAGCACAGCGGGCACACACTCGGCCAACTCATCAACGAGGAA AGGCTCCGACTCGGCGCCGAACTGCTCGTCACCACCGACGACACCATTGCCGAAATCACCCGAACCATTGGCTAC GAAAGTCCAGCCTATTTCCATAAACTCTTCCGCAGCCGCTACCTCATTACCCCCGACCGCTACCGCAACGACTTC CGTATCGCATTACGTTGCGGATGA

[0199] Suitably, the AraC gene may encode a protein shown as SEQ ID NO: 40 or a sequence with at least 80% sequence identity to SEQ ID NO: 40. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 40.

[0200] SEQ ID NO: 40 MERDAFRLPGLTAGDDNQYADHTLTGMAADAANVIAAGGPAPLTSFGTVAQAAHLNPDDGFGIIGHDLAHPSHLH RHDYMEITHAIAGTVLVWVEGETNVLTQGGTILIKPGARHLISPIIEYGQTPHEADILIKPELIRQCRIPILEAA GADRMFISWLDDDRQTHCLLAAGKHHAGEAAISRMFIAYCINATYRPDFTVIGNLLELFHETSRVLEHQPRTDPL IAAIIETITADPATAHNQAIADTLGYSVGYLSRYARKHSGHTLGQLINEERLRLGAELLVTTDDTIAEITRTIGY ESPAYFHKLFRSRYLITPDRYRNDFRIALRCG

[0201] Suitably, the B. longum subsp. iuvenis strain comprises a MFS transporter and an AraC family transcriptional regulator gene. Suitably, the B. longum subsp. iuvenis strain comprises a GH43_17, a MFS transporter and an AraC family transcriptional regulator gene. Suitably, the GH43_17, MFS transporter and AraC family transcriptional regulator genes are comprised in a gene cluster.

[0202] As used herein, a ‘gene cluster’ may refer to a group of genes that are located next to each other in a chromosome.

[0203] Suitably, the B. longum subsp. iuvenis strain comprises each of a GH31, an ABC transporter, a Lac-I type regulator, a MFS transporter and / or an AraC family transcriptional regulator gene.

[0204] Suitably, the B B. longum subsp. iuvenis strain comprises a GH43_17, a MFS transporter, an AraC, a GH31, an ABC transporter, and a Lac-I type regulator gene. Suitably, the GH43_17, MFS transporter, AraC family transcriptional regulator, GH31, ABC transporter, and Lac-I type regulator genes are comprised in aa gene cluster as described above.

[0205] Suitably, the B. longum subsp. iuvenis strain further comprises a xylulose kinase gene and / or a xylose isomerase gene. Suitably, the xylulose kinase gene and / or xylose isomerase genes are comprised in a gene cluster as defined above.

[0206] Suitably, the xylulose kinase gene comprises SEQ ID NO: 41 or a sequence with at least 60% sequence identity to SEQ ID NO: 41. Suitably, the xylulose kinase gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 41.

[0207] SEQ ID NO: 41 ATGACGAGAGTACTGGTTGCCGGCGTAGATACGTCAACTCAATCAACAAAGGTCCGCATTACGGACGC CGCCACCGGCGAACAGGTTCGGTTCGGGCAGGCCAAGCACCCGGATGGCACCTCGGTCAACCCGGAAT TCTGGTGGGAGGCCTTCACCAAGGCCGCCGAGCAGGCCGGCGGGCTTGACGATGTCGCGGCCCTCGCG GTTGGCGGCCAGCAGCATGGCATGGTCATTCTCGACAAGCAGGGCAACGTGATTCGCGATGCGATGCT CTGGAATGACACCAGTTCCGCCCCGCAGGCCGCCGCCCTGATCGACAAGCTCGGTGCAACTCCGGCCG AGGGCGACGAACCGGACGACGTGACCGCCCGCGGCAAGCAGCGCTGGGTCAAGGCCGTCGGGTCCTCC CCCGTCGCTTCCTACACGCTGACCAAGGTGGCGTGGGTGGCCGAGAACGAGCCTGAGAACGCCAAGAA GATTGCCGCCGTCTGTCTGCCGCACGATTGGCTGAGCTGGCGTATCGCCGGCTATGGCCCGGTGGCCG AGGGCGAGGACGCTCATCTCGAAGCCCTGTTCACCGACCGTTCCGACGCTTCCGGCACCATTTACTAC GATGCCGCGCATGACGAGTACCGCCGCGATCTCATCGCCATGGTGCTGACCCCCGCCGAGGGCGAGGA AGCCGCCAAGGCCCACGCCGACGCCATTGTGCTGCCCACCGTGCTGGGCCCGCATGAGGCAGCCGCCG TCAAGGCCGACCCCGCCATTGCCGGCAAGGACGTTGAAGGCGGCTGCATCATCGGCCCCGGCGGCGGA GACAATGCCATGGCCTCGCTGGGCCTCGGCATGGCCGTGGGCGATGTGTCCGTATCGCTCGGCACCTC CGGCGTGGCCGCGGCCATCGCTGAAAACCCGGTGTACGACCTGACCGGAGCGATTTCTGGCTTTGCCG ACTGCACCGGTCATTATCTGCCGCTTGCCTGCACCATCAACGGTTCGCGCATTCTGGACGCCGGTCGC GCCGCCCTTGGCGTGGACTACGACGAGCTGGCCGAACTGGCCTTTAAGGCCGAGCCGGGTGCCGGCGG CATCACCCTGGTGCCGTACTTCGACGGCGAGCGTACGCCGAACCGTCCGGACGCCACCGCCTCGCTGA CTGGCCTGACCCTGCACAACACCACCAAGGAGAATCTGGCTCGTGCGTTCGTCGAAGGCCTGCTGTGT TCCCAGCGCGACTGCCTCGAGCTGATTCGTTCGCTGGGTGCCGAGATCAACCGCATCCTGCTCATTGG CGGTGGCGCGAAGTCCGTGGCCATCCGCACGCTGGCCCCCTCAATCCTCGGCATGGACGTGACCCGTC CGGCCACCGACGAATATGTGGCCATCGGCGCCGCCCGTCAGGCCGCCTGGGTGCTGTCCGGCGAGGCC GAACCGCTGACCTGGCAACTCACCATCGAGGGCGTGGAGACCGGCGAGCCCACCGAAGCCGTGTACGA GGCATACGCCAAGGCGCGCGGCTGA

[0208] Suitably, the xylulose kinase gene may encode a protein shown as SEQ ID NO: 42 or a sequence with at least 80% sequence identity to SEQ ID NO: 42. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 42.

[0209] SEQ ID NO: 42 MTRVLVAGVDTSTQSTKVRITDAATGEQVRFGQAKHPDGTSVNPEFWWEAFTKAAEQAGGLDDVAALAVGGQQHG MVI LDKQGNVI RDAMLWNDTS SAPQAAALI DKLGATPAEGDEPDDVTARGKQRWVKAVGS S PVAS YTLTKVAWVA ENEPENAKKIAAVCLPHDWLSWRIAGYGPVAEGEDAHLEALFTDRSDASGTIYYDAAHDEYRRDLIAMVLTPAEG EEAAKAHADAIVLPTVLGPHEAAAVKADPAIAGKDVEGGCIIGPGGGDNAMASLGLGMAVGDVSVSLGTSGVAAA IAENPVYDLTGAISGFADCTGHYLPLACTINGSRILDAGRAALGVDYDELAELAFKAEPGAGGITLVPYFDGERT PNRPDATASLTGLTLHNTTKENLARAFVEGLLCSQRDCLELIRSLGAEINRILLIGGGAKSVAIRTLAPSILGMD VT RPAT DE YVAI GAARQAAWVL S GEAE P LTWQLT I EGVET GE PT EAVYEAYAKARG

[0210] Suitably, the xylose isomerase gene comprises SEQ ID NO: 43 or a sequence with at least 60% sequence identity to SEQ ID NO: 43. Suitably, the xylose isomerase gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 43.

[0211] SEQ ID NO: 43 ATGGGTCTGTGGGATGTTGACAAGATCGAGTACGTCGGCCGCGCCAAAGGACCGAAGGAAGACTTCGCCTTCCAT TACTACGATGCCGACAAGGTCGTTGCCGGCAAGAAGATGAAGGATTGGCTGCGCTTCGGCGTTGCTTGGTGGCAC ACCTTCAACCAGGAACTGGTTGATCCGTTCGGCACCGGCACCGCGCACCGCCCGTACTACAAGTACACCGATCCG ATGGACCAGGCTCTGGCCAAGGTCGACTACGCCTTCGAGCTGTTCCAGAAGCTGGGCGTCGAGTACTTCTGCTTC CACGATCGTGACATCGCCCCCGAAGGCGACACCCTGCGCGAGACCAACGCCAACCTCGACAAGGTCGTTGACAAG ATCGACGAGAATATGAAGTCCACCGGTGTCAAGCTGCTGTGGAACACCTCCTCCCTGTTCACCAACCCGCGCTTC GTGTCCGGCGCCGCCACTTCTCCGTTCGCCGACATCTACGCCTACGCCGGTGGCCAGCTCAAGAAGAGCTTGGAG ATCGGCAAGCGCCTGGGCGCCGAGAACTACGTGTTCTGGGGTGGCCGCGAAGGCTACGAGAACCTGTGGAACACC GAGATGAAGCGCGAGACCGACCACATCGCCAAGTTCTTCCACATGTGCGCAGATTACGCCAAGGAAATCGGCTTT GAGGCCCAGTTCCTGATCGAGCCGAAGCCGAAGGAGCCGACGCTGCACCAGTACGACTTCGATGCCGCCACCGCC ATCGAGTTCCTGCGCAACCACGACCTGACCGACGTCTTCAAGCTGAACTTGGAAGGCAACCACGCCAACCTGGCC GGCCACACCTACCAGCACGAGATCCGCGTGGCCCGCGAGTCCGGCTTCCTCGGTTCCCTCGACGCCAACCAGGGC GACAAGCTCATCGGCTGGGATATGGACGAGTTCCCGACCGATCTGTACGAGACCGTCGCCGTCATGTGGGAAGTC CTGCAGGCCGGCTCCATCGGACCTCACGGTGGTCTGAACTTCGACGCCAAGCCGCGCCGTACCTCCTTCTACGAG GAGGACCTGTTCCGCTCCCACATCGCCGGCATGGATGCCTACGCCGCCGGCCTGCTGGTTGCCGACAAGATGAAC CAGGACGGCTTCATCCAGAATCTTCAGGCCGAGCGCTACAGCTCCTACGACTCCGGCATCGGCAAGGACATCGAC GAGGGCAACGTCACCTTGGCCGACCTCGAAGCCTACAGCCTCGACAAGCCGCAGTCCGAGCTCATCGCCGCCACC AAGTCCGATCACCTCGAGTCCGTCAAGGCCACCATCAACAACTACATCATTGATGCCCTGGCTGAGGTCGAGTGA

[0212] Suitably, the xylulose isomerase gene may encode a protein shown as SEQ ID NO: 44 or a sequence with at least 80% sequence identity to SEQ ID NO: 44. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 44.

[0213] SEQ ID NO: 44 MGLWDVDKIEYVGRAKGPKEDFAFHYYDADKWAGKKMKDWLRFGVAWWHTFNQELVDPFGTGTAHRPYYKYTDP MDQALAKVDYAFELFQKLGVEYFCFHDRDIAPEGDTLRETNANLDKWDKIDENMKSTGVKLLWNTSSLFTNPRF VSGAATSPFADIYAYAGGQLKKSLEIGKRLGAENYVFWGGREGYENLWNTEMKRETDHIAKFFHMCADYAKEIGF EAQFLIEPKPKEPTLHQYDFDAATAIEFLRNHDLTDVFKLNLEGNHANLAGHTYQHEIRVARESGFLGSLDANQG DKLIGWDMDEFPTDLYETVAVMWEVLQAGSIGPHGGLNFDAKPRRTSFYEEDLFRSHIAGMDAYAAGLLVADKMN QDGFIQNLQAERYSSYDSGIGKDIDEGNVTLADLEAYSLDKPQSELIAATKSDHLESVKATINNYIIDALAEVE

[0214] Human milk oligosaccharide

[0215] Suitably, the present B. longum subsp. iuvenis strain preferentially utilizes 3- fucosyllactose (3-FL) compared to other B. longum subsp. iuvenis strains as demonstrated by a better growth.

[0216] Suitably, the present B. longum subsp. iuvenis strain may have a growth rate of at least 0.6 k when cultured in the presence of 3-FL. Suitably, the present B. longum subsp. iuvenis strain may have a growth rate of at least 0.7 k, at least 0.8 k or at least 0.9 k when cultured in the presence of 3-FL. Growth rate may be calculated by culturing a bacterium on a given substrate, or mixture of substrates, for a period of time and modelling the growth curve using a logistic growth model, to obtain the relative growth rate k. Without wishing to be bound by theory, preferential growth on 3-FL is considered to be advantageous as levels of 3-FL rise in human breastmilk during the weaning period. Preferential growth on 3-FL indicates that the present B. longum subsp. iuvenis strain may be particularly adapted to survive and grow in the microbiome during the weaning phase.

[0217] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 25 (GH25) gene. Suitably, the GH25 gene comprises SEQ ID NO: 45 or a sequence with at least 60% sequence identity to SEQ ID NO: 45. Suitably, the GH25 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 45.

[0218] SEQ ID NO: 45 ATGAGCAATCCAACAAATGATGGTATCAACTTGAATTACCTCGCAAACGTGCGTCCCTCGTCGCGACAGCTTGTC TGGCAGCGTATGGAGATGTATGCCTTCATACACTTCGGCATGAATACCATGACAGACAGGGAATGGGGTCTTGGG CATGAGGATCCGGCGCTGTTCGATCCACAGAATGTAGATGTGGAACAGTGGATGGATGCGCTGGTGGCTGGTGGA ATGACTGGTGTCATCTTGACGTGCAAGCATCATGATGGATTCTGCCTGTGGCCATCGCGTTACACGCAGCATACC GTTGCCGCCTCGCCGTGGAGGGACGGAAAAGGGGATCTCGTTCGTGAGGTCAGTGAGTCCGCCAGACGTCATGGA CTGAAGTTCGGCGTATACCTGTCTCCGTGGGATCGAACCGAAGAATCCTATGGCAAAGGCAAGGCATATGACGAT TTCTACGTCGGACAATTGACTGAGTTGCTCACCCAGTACGGACCGATTTTCTCCGTATGGCTGGATGGTGCCAAT GGTGAGGGCAAGAACGGCAAGACTCAGTATTACGACTGGGATCGTTACTACAACGTCATTCGTTCGCTTCAACCC AATGCGGTGATATCCGTATGCGGTCCCGACGTTCGCTGGGCTGGAAATGAAGCCGGACATGTACGTGACAACGAA TGGAGTGTCGTGCCCCGACGACTGCGTTCGGCGGAACTGACTATGGAAAATTCACAGCAGGAGGACGATGCGTCC TTTGCTTCTACGGTTCGCTCTCAAGATGACGACCTTGGAAGTCGTGAGGCGGTTTCCGGATACGGGGATGACGTC TGTTGGTACCCAGCTGAGGTCGATACCTCCATTCGCCCTGGATGGTTCTATCACAAGTATGAAGACGACAAGGTC ATGAGCGCAGATCAGCTTTTTGACCTCTGGCTTTCCGCAGTCGGCGGTAATTCGTCTCTTCTGCTCAATATTCCT CCGTCTCCAGAAGGACTGTTCGCAGAACCGGATGTGGAGTCGCTCAAGGGGCTGGGAAGCCGTATCAATGAATTC CGCAAAGCATTGGCTTCGTCTTGTTGCGAGGTCAAGACCAGCAGCGCGGACGAAACTGCAATGCGACTTCTCGAT GGGAATCAGGACACGTATTGGTCTCCTGATGCCAATGACGTGGCCCCTGCCGTCACGCTCACTTTCCCGCAGCTG ACGACGATCAATGCCGTTGTGGTTGAAGAGGCCATAGAGTATGGGCAGCGCATTGAACATATGCGCGTTACTGGT GTGCTATCTGATGGTACTGAGTGTGTACTCGGCCAGTTCGGCACAGTGGGATACCGCAGGATACTCCGCTTCGAC GATGTCGAAGTATCTTCGGTTACCCTACATGTGGATGATTCAAGGTTCACGCCAATGATCAGCCGTGCAGCTGCG GTGCGGATATAA

[0219] Suitably, the GH25 gene may encode a protein shown as SEQ ID NO: 46 or a sequence with at least 80% sequence identity to SEQ ID NO: 46. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 46.

[0220] SEQ ID NO: 46 MSNPTNDGINLNYLANVRPSSRQLVWQRMEMYAFIHFGMNTMTDREWGLGHEDPALFDPQNVDVEQWMDALVAGG MTGVILTCKHHDGFCLWPSRYTQHTVAASPWRDGKGDLVREVSESARRHGLKFGVYLSPWDRTEESYGKGKAYDD FYVGQLTELLTQYGPIFSVWLDGANGEGKNGKTQYYDWDRYYNVIRSLQPNAVISVCGPDVRWAGNEAGHVRDNE WSWPRRLRSAELTMENSQQEDDASFASTVRSQDDDLGSREAVSGYGDDVCWYPAEVDTSIRPGWFYHKYEDDKV MSADQLFDLWLSAVGGNSSLLLNIPPSPEGLFAEPDVESLKGLGSRINEFRKALASSCCEVKTSSADETAMRLLD GNQDTYWSPDANDVAPAVTLTFPQLTTINAVWEEAIEYGQRIEHMRVTGVLSDGTECVLGQFGTVGYRRILRFD DVEVS S VT LHVDD S RFT PMI S RAAAVRI

[0221] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family 95 (GH95) gene. Suitably, the GH95 gene comprises SEQ ID NO: 47 or a sequence with at least 60% sequence identity to SEQ ID NO: 47. Suitably, the GH95 gene comprises a sequence with at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 47.

[0222] SEQ ID NO: 47 ATGAAACTCACATTCGATGGAATCTCTTCGTGCTGGGAAGAAGGCATCCCGCTCGGCAACGGACGCATGGGAGCG GTCCTGTGTTCCGAACCGGAAACCGACGTGCTGTATCTCAACGACGACACCCTTTGGTCAGGATATCCACACGCG GAAACCTCGCCGGTGACGCCGGAGATTGTGGCCAAGGCACGCCAGGCGTCGTTGCAGGACGACTACACCGCCGCC ACGCGAATCATCAAGGAAGCCACACTGCAGGAAAAGGACGAACAGATTTACGAGCCATTCGGAACGGCCCGTATT CAGTACTCGACCCCTGCAGACGGCCGTGAGAGCATGAAACGCCAGCTGGATCTTGCAAGGGCGCTCGCCGGTGAA ACATTCCAGATGGGTGATGCCAACGTTCATGTCGACGCATGGTGCAGCGAGCCTGATGACCTGTTGGTCTACAGG ATGTCATCGGATGCGCCGGTTGATGTGAACATCAGTGTCGCCGGCACTTTCCTCAAACAATCGCGCGCCTCGTTG GAAACGGTATCCGACGGTCATCGGGCCACACTCGTCGTCATGGGCCGGATGCCTGGACTCAACATCGGGCTCCTC CCTCATCCTTCCGAACATCCTTGGGAAGATGAGCAGGACGGAACCGGAATGGCGTACGCCGGTGCGTTCTCCCTT ACCGTCACAGGTGGCGACATCAATGTGGACGACAACAGTCTGCAATGTTCGCACATCACCGGATTATCGCTCCGC TTCCGCAGTATGAGCGGATTCAAGGGAAGCGACCAGCAGCCGGAACGAAGCATGACGGTTATCGCCGACCATCTG GAGAAAACCATCGACGAGTGGTCGACCGACCTGCAGACCATGCTCGACCGCCATATCGCGGACTACCGCAGATAT TTCGACAGGGTGGCCATCCATCTCGGTTCAGCCCATGATGACGATACGGAACTACCGTTCTCGGCGATCCTTCGC TCGGATGAGAACAAAGAACCGCATCGTCTGGAGATGCTGGCGGAGGCAATGTTCGATTTCGGCCGGTATATGCTT ATCTCCTCGTCCAGGCCACACACCCAGCCGGCGAATCTGCAGGGGATTTGGAACCATAAGGACTTCCCAAACTGG TACAGCGCCTACACGACGAACATCAACGTCGAGATGAACTATTGGATGACCGGCCCCTGCGCGCTCAAGGAGCTC ATCGAGCCGCTCGTCTCCATGAATGAGGAGCTGCTGGCACCGGGGCACGATGCCGCTGACAGGATTCTCGGCTGC CGAGGATCGGCTGTCTTCCATAATGTCGATCTCTGGCGTAGGGCCCTTCCTGCGAACGGCGATCCGATGTGGGCG TTCTGGCCGTTCGGCCAGGCATGGATGTGCCGGAACCTGTTCGATGAATATCTGTTCAACCAGGATGCATCGTAC CTGGCCCGCATCTGGCCGATCATGCGGGACAACGCGCGATTCTGCATGGATTTCCTATCGGAGACAGAGCATGGG CTGGCCCCGTCCCCTGCAACATCACCGGAGAACTGTTTCCTGGTGAACGGAGAACCGGTATCCGTTGCGCAAAGC AGTGAGAATGCCACGGCCATCGTGCGTAATCTGCTTGATGATTTGATTCAGGCTTCTCACGATCTGGAAAACCTT GACGAAGAGGACAGAAATCTGGTCCGTGAAGCGGAATCCGTCCGTTCCCAACTGGCTGAAACGCGATTGGGAGCT GATGGAAGAGTCCTTGAATGGAACGACGAATTCATCGAATCCGATCCACAGCACCGCCATCTGTCCCACCTTTAC GAACTGCATCCTGGTGCAGGCATCACGTCTAAGACTCCGCGTCTGGAGGAAGCCGCGAGAAAATCCCTCGAAGTG CGTGGCGATGATGGTTCCGGTTGGAGCATCGTATGGCGCATGATCATGTGGGCACGTCTGCGTGATGCGGAACAC GCCAAACGAATCATAGGCATGTTCCTACGGCCGGTGGATGCGAACGCTGAAACCAATCTGCTGGGCGGAGGAGTG TACGACAGCGGATTATGCGCCCACCCGCCGTTCCAGATCGACGGGAACCTTGGATTCCCGGCGGCCTTGTCGGAG ATGCTCGTCCAAAGCCACGATGGCTGGATTCGCGTTCTTCCGGCCCTGCCGGAGGATTGGCATGAGGGAAGCTTC CATGCGCTCCGCGCAAGAGGTGGAATCCAAGTGGATGCGACCTGGACGGATCAGACAGTGGAATATACGTTGCGC TGTTCGAAGCCCACGGAGATTACGCTGAACGTTCTGGGGACTGATATGGGACGTGTCGCATTGTCTCCGGATAAG CCATTCAAGGGAACCATCCGGCGTTAA

[0223] Suitably, the GH95 gene may encode a protein shown as SEQ ID NO: 48 or a sequence with at least 80% sequence identity to SEQ ID NO: 48. Suitably, the protein may comprise a sequence with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 48.

[0224] SEQ ID NO: 48 MKLTFDGISSCWEEGIPLGNGRMGAVLCSEPETDVLYLNDDTLWSGYPHAETSPVTPEIVAKARQASLQDDYTAA TRIIKEATLQEKDEQIYEPFGTARIQYSTPADGRESMKRQLDLARALAGETFQMGDANVHVDAWCSEPDDLLVYR MSSDAPVDVNISVAGTFLKQSRASLETVSDGHRATLWMGRMPGLNIGLLPHPSEHPWEDEQDGTGMAYAGAFSL TVTGGDINVDDNSLQCSHITGLSLRFRSMSGFKGSDQQPERSMTVIADHLEKTIDEWSTDLQTMLDRHIADYRRY FDRVAIHLGSAHDDDTELPFSAILRSDENKEPHRLEMLAEAMFDFGRYMLISSSRPHTQPANLQGIWNHKDFPNW YSAYTTNINVEMNYWMTGPCALKELIEPLVSMNEELLAPGHDAADRILGCRGSAVFHNVDLWRRALPANGDPMWA FWPFGQAWMCRNLFDEYLFNQDASYLARIWPIMRDNARFCMDFLSETEHGLAPSPATSPENCFLVNGEPVSVAQS SENATAIVRNLLDDLIQASHDLENLDEEDRNLVREAESVRSQLAETRLGADGRVLEWNDEFIESDPQHRHLSHLY ELHPGAGITSKTPRLEEAARKSLEVRGDDGSGWSIVWRMIMWARLRDAEHAKRIIGMFLRPVDANAETNLLGGGV YDSGLCAHPPFQIDGNLGFPAALSEMLVQSHDGWIRVLPALPEDWHEGSFHALRARGGIQVDATWTDQTVEYTLR CSKPTEITLNVLGTDMGRVALSPDKPFKGTIRR

[0225] Suitably, the present B. longum subsp. iuvenis may comprise a GH25 and a GH95 gene as defined herein.

[0226] Lacto-N-fucopentaose I (LNFP-I)

[0227] Among the fucosylated HMO glycans in breastmilk is the pentasaccharide lacto-N-fucopentaose I (LNFP-I). HMO glycans are already included as prebiotics in a number of infant formulae and supplements. However, LNFP-I has not been included in such compositions due to challenges around its efficient industrial production at scale. Advances in biotechnology and glycobiology are removing these barriers.

[0228] The present inventors have surprisingly found that the presence of LNFP-I as a carbohydrate source can support the growth of B. longum subsp. iuvenis and further boost the production of beneficial metabolites in a synergistic manner.

[0229] The composition or combination of the invention comprises lacto-N-fucopentaose I (LNFP-I).

[0230] In some embodiments, LNFP-I is present in a total amount of from 10 mg / L to 5000 mg / L of the composition or combination according to the invention or of from 0.01 g / 100 g to 4 g / 100 g of the nutritional composition or combination according to the invention.

[0231] In some embodiments, LNFP-I is present in a total amount of from 25 mg / L to 4000 mg / L of the composition or combination according to the invention or of from 0.02 g / 100 g to 3.75 g / 100 g of the nutritional composition or combination according to the invention. Suitably, LNFP-I is present in a total amount of from 50 mg / L to 2500 mg / L, for example from 60 mg / L to 2000 mg / L, for example from 80 mg / L to 1500 mg / L, for example from 100 mg / L to 1000 mg / L, for example from 200 mg / L to 800 mg / L of the composition or combination according to the invention. Suitably, LNFP-I is present in a total amount of from 0.04 g / 100 g to 2 g / 100 g, for example from 0.05 g / 100 g to 1.6 g / 100 g, for example from 0.06 to 1.2 g / 100g, for example from 0.07 g / 100 g to 0.8 g / 100 g, for example from 0.1 g / 100g to 0.7 g / 100g of the composition or combination (dry weight).

[0232] In one embodiment, the composition or combination comprises from 0.015 wt.% to 3.8 wt.%, preferably from 0.08 wt.% to 1.2 wt.%, of lacto-N-fucopentaose I (LNFP-I) of the total wt.% of the composition or combination.

[0233] LNFP-I may be isolated by chromatography or filtration technology from a natural source such as animal milks. Suitably, the animal milk as used herein may be cow, sheep, goat, camel or buffalo milk. Preferably, the animal milk is cow’s milk. Preferably, the LNFP-I may be produced by biotechnological means using specific fucosyltransferases and / or fucosidases either through the use of enzyme-based fermentation technology (recombinant or natural enzymes) or microbial fermentation technology. In the latter case, microbes may either express their natural enzymes and substrates or may be engineered to produce respective substrates and enzymes. Single microbial cultures and / or mixed cultures may be used. Fucosylated oligosaccharide formation can be initiated by acceptor substrates starting from any degree of polymerization (DP), from DP = 1 onwards. Suitable techniques for producing LNFP-I are known in the art (see, for example, Hu et al., Carbohydr Polym, 2022, 297: 120017 and Derya et al., J Biotechnol., 2020, 318: 31-38). Alternatively, LNFP-I may be produced by chemical synthesis from lactose as initial acceptor substrate building an LNT backbone and free fucose as final donor substrate or by starting from LNT for example, produced by biotechnology or chemical synthesis, and using fucose. Fucosylated oligosaccharides are also available for example from DSM of the Netherlands (for example, GlyCare™ 3FL 9001 and GlyCare™ LNFP-I / 2FL 8001) or from Elicityl of France (for example, 2FL, 3FL, DFL, LNFP-I).

[0234] HMO mixture

[0235] The composition or combination of the invention comprises a HMO mixture consisting of 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT). The composition or combination of the invention also comprises a HMO mixture consisting of 2'-fucosyl lactose (2FL) and 3-fucosyllactose (3FL).

[0236] In some embodiments, the HMO mixture consists of 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), and 3-fucosyllactose (3FL).

[0237] In some embodiments, the HMO mixture consists of 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), and lacto-N-neotetraose (LNnT).

[0238] In some embodiments, the HMO mixture consists of 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), 3-fucosyllactose (3FL), and lacto-N-neotetraose (LNnT).

[0239] In one embodiment, the HMO mixture comprises 2FL in an amount of from 16 wt% to 85 wt%. Suitably, the HMO mixture may comprise 2FL in an amount of from 31 wt% to 82 wt%, preferably from 41wt% to 70 wt%. Suitably, the HMO mixture may comprise 2FL in an amount of from 16 wt% to 69 wt%, preferably from 22 wt% to 59 wt%. Suitably, the HMO mixture may comprise 2FL in an amount of from 34 wt% to 85 wt%, preferably from 40 wt% to 71 wt%. Suitably, the HMO mixture may comprise 2FL in an amount of from 20 wt% to 60 wt%, preferably from 22 wt% to 55 wt%.

[0240] In one embodiment, the HMO mixture comprises LNT in an amount of from 4 wt% to 40 wt%. Suitably, the HMO mixture may comprise LNT in an amount of from 10 wt% to 27 wt%, preferably from 14 wt% to 23 wt%. Suitably, the HMO mixture may comprise LNT in an amount of from 9 wt% to 24 wt%, preferably 12 wt% to 21 wt%. Suitably, the HMO mixture may comprise LNT in an amount of from 10 wt% to 40 wt%, preferably 12 wt% to 26 wt%. Suitably, the HMO mixture may comprise LNT in an amount of from 4 wt% to 30 wt%, preferably 6 wt% to 20 wt%.

[0241] In one embodiment, the HMO mixture comprises DFL in an amount of from 1 wt% to 14 wt%. Suitably, the HMO mixture may comprise DFL in an amount of from 4 wt% to 11 wt%, preferably from 6 wt% to 10 wt%. Suitably, the HMO mixture may comprise DFL in an amount of from 2 wt% to 10 wt%, preferably from 3 wt% to 8 wt%. Suitably, the HMO mixture may comprise DFL in an amount of from 4 wt% to 14 wt %, preferably from 5 wt% to 10 wt%. Suitably, the HMO mixture may comprise DFL in an amount of from 1 wt% to 12 wt %, preferably from 2 wt% to 8 wt%. In one embodiment, the HMO mixture comprises 6SL and 3SL combined in an amount of from 7 wt% to 34 wt%. Suitably, the HMO mixture may comprise 6SL and 3SL combined in an amount of from 9 wt% to 34 wt%, preferably from 11 wt% to 29 wt%. Suitably, the HMO mixture may comprise 6SL and 3SL combined in an amount of from 8 wt% to 26 wt%, preferably from 11 wt% to 22 wt%. Suitably, the HMO mixture may comprise 6SL and 3SL combined in an amount of from 9 wt% to 31 wt%, preferably from 10 wt% to 28 wt%. Suitably, the HMO mixture may comprise 6SL and 3SL combined in an amount of from 7 wt% to 23 wt%, preferably from 8 wt% to 22 wt%.

[0242] In one embodiment, the HMO mixture comprises 3FL in an amount of from 10 wt% to 50 wt%. Suitably, the HMO mixture may comprise 3FL in an amount of from 10 wt% to 50 wt%, preferably from 11 wt% to 43 wt%. Suitably, the HMO mixture may comprise 3FL in an amount of from 10 wt% to 50 wt%, preferably from 13 wt% to 46 wt%.

[0243] In one embodiment, the HMO mixture comprises LNnT in an amount of from 6 wt% to 30 wt%. Suitably, the HMO mixture may comprise LNnT in an amount of from 6 wt% to 30 wt%, preferably from 7 wt% to 22 wt%. Suitably, the HMO mixture may comprise LNnT in an amount of from 3 wt% to 25 wt%, preferably from 5 wt% to 20 wt%.

[0244] In some embodiments, the HMO mixture consists or consists essentially of:

[0245] i. 16 wt% to 69 wt% of 2FL;

[0246] ii. 9 wt% to 24 wt% of LNT;

[0247] iii. 2 wt% to 10 wt% of DFL;

[0248] iv. 8 wt% to 26 wt% of 6SL and 3SL combined; and

[0249] v. 10 wt% to 50 wt% of 3FL.

[0250] In some preferred embodiments, the HMO mixture consists or consists essentially of:

[0251] i. 22 wt% to 59 wt% of 2FL;

[0252] ii. 12 wt% to 21 wt% of LNT;

[0253] iii. 3 wt% to 8 wt% of DFL;

[0254] iv. 11 wt% to 22 wt% of 6SL and 3SL combined; and

[0255] v. 11 wt% to 43 wt% of 3FL.

[0256] In some embodiments, the HMO mixture consists or consists essentially of:

[0257] i. 34 wt% to 85 wt% of 2FL;

[0258] ii. 10 wt% to 40 wt% of LNT;

[0259] iii. 4 wt% to 14 wt% of DFL; iv. 9 wt% to 31 wt% of 6SL and 3SL combined; and

[0260] v. 6 wt% to 30 wt% of LNnT.

[0261] In some preferred embodiments, the HMO mixture consists or consists essentially of:

[0262] i. 40 wt% to 71 wt% of 2 FL;

[0263] ii. 12 wt% to 26 wt% of LNT;

[0264] iii. 5 wt% to 10 wt% of DFL; and

[0265] iv. 10 wt% to 28 wt% of 6SL and 3SL combined; and

[0266] v. 7 wt% to 23 wt% of LNnT.

[0267] In some embodiments, the HMO mixture consists or consists essentially of:

[0268] i. 20 wt% to 60 wt% of 2FL;

[0269] ii. 4 wt% to 30 wt% of LNT;

[0270] iii. 1 wt% to 12 wt % of DFL;

[0271] iv. 7 wt% to 23 wt% of 6SL and 3SL combined;

[0272] v. 10 wt% to 50 wt% of 3FL; and

[0273] vi. 3 wt% to 25 wt% of LNnT.

[0274] In some preferred embodiments, the HMO mixture consists or consists essentially of:

[0275] i. 22 wt% to 55 wt% of 2 FL;

[0276] ii. 6 wt% to 20 wt% of LNT;

[0277] iii. 2 wt% to 8 wt % of DFL;

[0278] iv. 8 wt% to 22 wt% of 6SL and 3SL combined;

[0279] v. 13 wt% to 46 wt% of 3FL and

[0280] vi. 5 wt% to 20 wt% of LNnT.

[0281] In the context of the present invention, the LNFP-I and the HMO mixture combined may be collectively referred to as a HMO mixture consisting of:

[0282] LNFP-I, 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0283] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0284] This terminology may be used interchangeably.

[0285] In some embodiments, the HMO mixture consists or consists essentially of: i. 20 wt% to 46 wt% of 2FL;

[0286] ii. 11 wt% to 17 wt% of LNT;

[0287] iii. 2 wt% to 7 wt% of DFL;

[0288] iv. 9 wt% to 21 wt% of 6SL and 3SL combined;

[0289] v. 9 wt% to 34 wt% of 3FL; and

[0290] vi. 5 wt% to 32 wt% of LNFP-I.

[0291] In some preferred embodiments, the HMO mixture consists or consists essentially of:

[0292] i. 22 wt% to 42 wt% of 2FL;

[0293] ii. 12 wt% to 15 wt% of LNT;

[0294] iii. 3 wt% to 6 wt% of DFL;

[0295] iv. 9 wt% to 19 wt% of 6SL and 3SL combined;

[0296] v. 11 wt% to 32 wt% of 3FL; and

[0297] vi. 10 wt% to 19 wt% of LNFP-I.

[0298] In some embodiments, the HMO mixture consists or consists essentially of:

[0299] i. 27 wt% to 41 wt% of 2FL;

[0300] ii. 8 wt% to 15 wt% of LNT;

[0301] iii. 4 wt% to 6 wt% of DFL;

[0302] iv. 8 wt% to 18 wt% of 6SL and 3SL combined;

[0303] v. 13 wt% to 21 wt% of LNnT; and

[0304] vi. 7 wt% to 33 wt% of LNFP-I.

[0305] In some preferred embodiments, the HMO mixture consists or consists essentially of:

[0306] i. 32 wt% to 39 wt% of 2 FL;

[0307] ii. 10 wt% to 14 wt% of LNT;

[0308] iii. 4 wt% to 6 wt% of DFL;

[0309] iv. 7 wt% to 15 wt% of 6SL and 3SL combined;

[0310] v. 16 wt% to 20 wt% of LNnT; and

[0311] vi. 11 wt% to 23 wt% of LNFP-I.

[0312] In some embodiments, the HMO mixture consists or consists essentially of:

[0313] i. 29 wt% to 40 wt% of 2FL;

[0314] ii. 8 wt% to 13 wt% of LNT;

[0315] iii. 3 wt% to 11 wt % of DFL;

[0316] iv. 3 wt% to 15 wt% of 6SL and 3SL combined; v. 11 wt% to 35 wt% of 3FL;

[0317] vi. 1 wt% to 18 wt% of LNnT; and

[0318] vii. 2 wt% to 24 wt% of LNFP-I.

[0319] In some preferred embodiments, the HMO mixture consists or consists essentially of:

[0320] i. 32 wt% to 39 wt% of 2 FL;

[0321] ii. 9 wt% to 12 wt% of LNT;

[0322] iii. 3 wt% to 11 wt % of DFL;

[0323] iv. 4 wt% to 15 wt% of 6SL and 3SL combined;

[0324] v. 12 wt% to 35 wt% of 3FL;

[0325] vi. 1 wt% to 17 wt% of LNnT; and

[0326] vii. 4 wt% to 14 wt% of LNFP-I.

[0327] When the composition or combination is in liquid form, the total HMO concentration is typically in the range from 0.5 to 10 g / L, preferably in the range from 1 to 7.5 g / L. Specific examples of the concentration level of total HMO, when the composition or combination is in liquid form, include 1 to 5 g / L, 1 to 4 g / L, 2 to 5 g / L, 1 to 3 g / L or 2 to 4 g / L.

[0328] When the composition or combination is in solid form, the total HMO concentration is typically in the range from 0.35 to 7 wt% (g total HMO / 100 g dry composition), preferably in the range from 0.35 to 5 wt%. Specific examples of the concentration level of total HMO, when the composition or combination is in dry form, include 0.5 to 3.5 wt% (g total HMO per 100 g dry composition), 0.5 to 2.5 wt%, 1 to 3.5 wt%, 0.5 to 2 wt% or 1 to 2.5 wt%.

[0329] Further probiotics

[0330] Bifidobacterium lonqum subsp. infantis

[0331] In some embodiments, the composition or combination of the invention further comprises Bifidobacterium longum subsp. infantis.

[0332] Bifidobacterium longum is a bacterium of the Bifidobacterium genus which is present in the human gastrointestinal tract. In 2002, three previously distinct species of Bifidobacterium, B. infantis, B. longum, and B. suis, were unified into a single species named B. longum with the biotypes infantis, longum, and suis, respectively (Sakata, S., et al., 2002. International journal of systematic and evolutionary microbiology, 52(6), pp.1945-1951).

[0333] Any suitable Bifidobacterium longum subsp. infantis strain may be used in the present invention. Such strains will be well-known to the skilled person. Suitable strains include Bifidobacterium longum subsp. infantis LMG 11588 (also known as Bifidobacterium longum subsp. infantis NCC3039 or Bifidobacterium longum subsp. infantis ATCC 17930) and Bifidobacterium longum subsp. infantis ATCC 15697 (also known as Bifidobacterium longum subsp. infantis NCC 3078).

[0334] The Bifidobacterium longum subsp. infantis may be a strain having at least 95%, at least 96%, at least 97%, at least 98%, at least 99% (suitably, at least 99.9%) ANI to Bifidobacterium longum subsp. infantis strain known to the skilled person.

[0335] Suitably, the Bifidobacterium longum subsp. infantis has at least 95%, at least 96%, at least 97%, at least 98%, at least 99% (suitably, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%) ANI to Bifidobacterium longum subsp. infantis LMG 11588 (also known as Bifidobacterium longum subsp. infantis NCC3039 or Bifidobacterium longum subsp. infantis ATCC 17930). Preferably, the Bifidobacterium longum subsp. infantis has at least 99.9% ANI to Bifidobacterium longum subsp. infantis LMG 11588.

[0336] An example of a microorganism genome that has at least 99.9% ANI with B. longum subsp. infantis LMG 11588 can be found in PATRIC (https: / / www.patricbrc.org), genome ID 1678.111. Hence, suitably the B. longum subsp. infantis having the PATRIC genome ID 1678.111 may be used in the present invention.

[0337] Bifidobacterium longum subsp. infantis LMG 11588 is sold by the Belgian Coordinated Collections of Microorganisms (BCCM) under the LMG accession number LMG 11588.

[0338] Bifidobacterium longum subsp. infantis ATCC 15697 is sold by the American Type Culture Collection (ATCC) under the accession number ATCC 15697.

[0339] The composition or combination according to the invention may contain from 103to 1012cfu of Bifidobacterium longum subsp. infantis, more preferably from 107toand 1012cfu such as from 108to 1010cfu of Bifidobacterium longum subsp. infantis per g of composition or combination on a dry weight basis. Suitably, the Bifidobacterium longum subsp. infantis is administered to the subject in an amount of at least about 106cfu / day, at least about 107cfu / day, or at least about 108cfu / day. Suitably, the Bifidobacterium longum subsp. infantis is administered to the subject in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less.

[0340] In one embodiment, the Bifidobacterium longum subsp. infantis is viable. Bifidobacterium animalis subsp. lactis

[0341] In some embodiments, the composition or combination of the invention further comprises Bifidobacterium animalis subsp. lactis.

[0342] Any suitable Bifidobacterium animalis subsp. lactis (B. lactis) strain may be used in the present invention. Such strains will be well-known to the skilled person. Suitable strains include Bifidobacterium animalis subsp. lactis CNCM I-3446.

[0343] The Bifidobacterium animalis subsp. lactis may be a strain having at least 95%, at least 96%, at least 97%, at least 98%, at least 99% (suitably, at least 99.9%) ANI to a Bifidobacterium animalis subsp. lactis strain known to the skilled person.

[0344] Suitably, the Bifidobacterium animalis subsp. lactis has at least 95%, at least 96%, at least 97%, at least 98%, at least 99% (suitably, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%) ANI to Bifidobacterium animalis subsp. lactis CNCM I-3446. Preferably, the Bifidobacterium animalis subsp. lactis has at least 99.9% ANI to Bifidobacterium animalis subsp. lactis CNCM I-3446.

[0345] Bifidobacterium lactis CNCM I-3446 was deposited with the Collection Nationale de Cultures de Microorganismes (CNCM), Institut Pasteur (INSTITUT PASTEUR, 25 RUE DU DOCTEUR ROUX, F-75724 PARIS CEDEX 15, FRANCE) by NESTEC S. A. (NESTEC S. A., AVENUE NESTLE 55, CH-1800 VEVEY) according to the Budapest Treaty on 7thJune 2005 receiving the deposit number CNCM I-3446.

[0346] The composition or combination according to the invention may contain from 103to 1012cfu of Bifidobacterium animalis subsp. lactis, more preferably from 107to 1012cfu such as from 108to1010cfu of Bifidobacterium animalis subsp. lactis per g of composition or combination on a dry weight basis. Suitably, the Bifidobacterium animalis subsp. lactis is administered to the subject in an amount of at least about 106cfu / day, at least about 107cfu / day, or at least about 108cfu / day. Suitably, the Bifidobacterium animalis subsp. lactis is administered to the subject in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less.

[0347] The composition or combination according to the invention may contain from 103to 1012cfu of Bifidobacteria (e.g. a combination of Bifidobacterium longum subsp. infantis and Bifidobacterium animalis subsp. lactis) more preferably from 107to 1012cfu such as from 108to 1010cfu of Bifidobacteria (e.g. of a combination of Bifidobacterium longum subsp. infantis and Bifidobacterium animalis subsp. lactis) per g of composition or combination on a dry weight basis. Suitably, the Bifidobacteria (e.g. a combination of Bifidobacterium longum subsp. infantis and Bifidobacterium animalis subsp. lactis) are administered to the subject in an amount of at least about 106cfu / day, at least about 107cfu / day, or at least about 108cfu / day. Suitably, the Bifidobacteria (e.g. a combination of Bifidobacterium longum subsp. infantis and Bifidobacterium animalis subsp. lactis) are administered to the subject in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less.

[0348] In one embodiment, the Bifidobacterium animalis subsp. lactis is viable.

[0349] Therapeutic use

[0350] The present inventors have surprisingly found that the combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture can synergistically increase production of one or more beneficial metabolites, such as amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, and nitrogenous organic compounds, or derivatives thereof, in the gastrointestinal tract, e.g. the intestine, of a subject.

[0351] As described below, each of amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, and nitrogenous organic compounds are beneficial metabolites associated with improving health, and / or treating and / or preventing disease.

[0352] In a first aspect, the invention provides the composition or combination of the invention for use in therapy in a subject, optionally by promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, or derivatives thereof, in the gastrointestinal tract of the subject.

[0353] In a further aspect, the invention provides the composition or combination of the invention for use in therapy in a subject, optionally by promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, in the gastrointestinal tract of the subject.

[0354] In a further aspect, the invention provides the composition or combination of the invention for use in promoting bone growth and / or bone development in a subject, optionally by promoting the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject. In some preferred embodiments, the therapy is promoting bone development, such as bone growth and / or bone strength and / or bone quality.

[0355] In a further aspect, the invention provides the use of a composition or combination according to the invention for the manufacture of a medicament for a subject, for example by promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, and nitrogenous organic compounds, or derivatives thereof, in the gastrointestinal tract of the subject.

[0356] In a further aspect, the invention provides the use of a composition or combination of the invention for the manufacture of a medicament for promoting bone growth and / or bone development in a subject, optionally by promoting the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0357] In a further aspect, the invention provides a method of promoting bone growth and / or bone development in a subject, optionally by promoting the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject, the method comprising administering a combination or composition of the invention to the subject.

[0358] Amino acids, peptides and proteins

[0359] In some embodiments, the composition or combination of the invention promotes the production of at least one amino acid, peptide and / or protein, or derivatives thereof, in the gastrointestinal tract of a subject.

[0360] Amino acid, peptide and protein derivatives and associated metabolites (e.g. polyamines, indole compounds, phenols, etc) have various health benefits. For example, amino acid derivatives, such as indoles, exert anti-microbial properties. They are thought to reinforce the epithelial barrier integrity thus playing a key role in improving gastro-intestinal health (Front Immunol. 2022 Jun 17; 13:903526).

[0361] In one aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one amino acid, peptide and / or protein in the gastrointestinal tract of the subject.

[0362] In another aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one amino acid in the gastrointestinal tract of the subject. In another aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one peptide in the gastrointestinal tract of the subject.

[0363] In another aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one protein in the gastrointestinal tract of the subject.

[0364] In a further aspect, the invention provides the composition or combination of the invention for use in promoting bone growth and / or bone development in a subject, by promoting the production of at least one amino acid, peptide and / or protein in the gastrointestinal tract of the subject.

[0365] Vitamin

[0366] In some embodiments, the composition or combination of the invention promotes the production of at least one vitamin in the gastrointestinal tract of a subject.

[0367] Vitamins can modulate the gut microbiome via several mechanisms, and as such display a diverse array of health benefits. For example, vitamins have anti-microbial properties, participate in energy generation, restore bone health among many other health benefits (Nutr Res. 2021 Nov;95:35-53).

[0368] In one aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one vitamin in the gastrointestinal tract of the subject.

[0369] In a further aspect, the invention provides the composition or combination of the invention for use in promoting bone growth and / or bone development in a subject, by promoting the production of at least one vitamin in the gastrointestinal tract of the subject.

[0370] Nucleotides

[0371] In some embodiments, the composition or combination of the invention promotes the production of at least one nucleotides and / or associated metabolites in the gastrointestinal tract of a subject.

[0372] Nucleotides and associated metabolites have a crucial role in cellular and energy metabolism as well as protein synthesis. They exert significant effects on cell proliferation and differentiation, particularly those found in the immune system and gastrointestinal tract (Nutr J. 2006 Jun 8;5:16). In one aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one nucleotide or associated metabiolites in the gastrointestinal tract of the subject.

[0373] In a further aspect, the invention provides the composition or combination of the invention for use in promoting bone growth and / or bone development in a subject, by promoting the production of at least one nucleotide or associated metabolites in the gastrointestinal tract of the subject.

[0374] Bile acids

[0375] In some embodiments, the composition or combination of the invention promotes the production of at least one bile acid in the gastrointestinal tract of a subject.

[0376] Bile acids have significant influence over the metabolism of macronutrients (lipids, carbohydrates, proteins) as well as the overall balance between pro-inflammatory and antiinflammatory responses in the body (Signal Transduct Target Ther. 2024 Apr 26;9(1):97). Thus, bile acids may exert various health benefits in a subject.

[0377] In one aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one bile acid in the gastrointestinal tract of the subject.

[0378] In a further aspect, the invention provides the composition or combination of the invention for use in promoting bone growth and / or bone development in a subject by promoting the production of at least one bile acid in the gastrointestinal tract of the subject.

[0379] Neurotransmitters

[0380] In some embodiments, the composition or combination of the invention promotes the production of at least one neurotransmitter in the gastrointestinal tract of a subject.

[0381] Neurotransmitters play a vital role in transmitting information within the central nervous system (CNS) and peripheral nervous system. These chemical messengers are crucial for the proper functioning of the brain, as they regulate neuronal growth, differentiation, and survival. They can influence various functions including emotions, movements, sleep patterns and are essential in the gut-brain axis (Int J Mol Sci. 2022 May 25;23(11):5954).

[0382] In a first aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one neurotransmitter in the gastrointestinal tract of the subject. SCFA

[0383] In some embodiments, the composition or combination of the invention promotes the production of SCFA in the gastrointestinal tract of a subject, for example when the HMO mixture consists of LNFP-I, 2FL, DFL, LNT, 6SL, 3SL, and 3FL. Preferably, the composition or combination of the invention increases the total SCFA levels in the gastrointestinal tract of a subject.

[0384] Suitably, the SCFA may be selected from acetate (Ethanoate, C1:0), butyrate (Butanonate, C4:0) and / or propionate (Propanoate, C3:0). Suitably, the composition or combination of the invention increases the total SCFA levels in the gastrointestinal tract of a subject. Suitably, ‘total SCFA’ refers to the sum of acetate, butyrate and propionate.

[0385] SCFAs may be produced, for example, by fermentation of dietary fiber, such as oligosaccharides (e.g. HMOs of the invention), in the gut (e.g. by Bifodobacteria).

[0386] SCFAs and their derivatives contribute to the preservation of intestinal mucosa integrity, enhance glucose and lipid metabolism, regulate energy expenditure, and modulate the immune system.

[0387] SCFAs have diverse physiological roles in body functions; they can affect the production of lipids, energy and vitamins; affect appetite and cardiometabolic health; and have roles in lowering blood pressure in experimental models. SCFAs have been shown to have an important role in preventing and / or controlling a number of infections and immune responses (Cell Host & Microbe; 2016; 20(2); 202-214). For example, SCFAs have been shown to have a protective affect against RSV (Nat Comm; 2019; 10; 3273); influenza virus (Immunity; 2018; 48(5); 992-1005 and PNAS; 2018; 16(8); 3118-3125); viral bronchiolitis (J Exp Med; 2018; 215(2); 537-557) and general microbe infection (Immunity; 2019; 50(2); 432-445).

[0388] Notably, SCFA produced in the gut impacts systemic levels and local SFCA levels in other local organs, for example, the lungs. The SCFA effects mediated by the composition or combination of the invention may be systemic. As such, the effects may systemically prevent or reduce the risk of an infection as described herein. The SCFA effects may occur locally in the gut, the lungs and / or the skin of the subject. Suitably, the SCFA effects may occur in the gut of the subject. Suitably, the SCFA effects may occur in the lungs of the subject. Accordingly, the SCFA effects may improve the health of a particular organ or system or prevent or reduce the risk of an infection in a particular organ or system.

[0389] The production of short-chain fatty acids (SCFAs), particularly acetate, by the gut microbiota plays a pivotal role in systemic physiological processes, including bone development and maintenance. SCFAs are primarily generated through the fermentation of dietary fibers by anaerobic bacteria in the colon. Among these, acetate is the most abundant, accounting for approximately 60% of total SCFAs, followed by propionate and butyrate. These metabolites are absorbed and distributed systemically, where they exert regulatory effects on various tissues, including bone.

[0390] SCFAs influence bone metabolism through several mechanisms. They act as signaling molecules via G-protein coupled receptors (GPR41, GPR43, and GPR109A), which are expressed on immune cells, epithelial cells, and bone-resident cells. Activation of these receptors by SCFAs modulates immune responses and inflammation, both of which are critical in bone remodeling. In particular, GPR43 activation by acetate has been shown to promote the differentiation of regulatory T cells and suppress pro-inflammatory cytokines, thereby creating a favorable environment for osteogenesis (Mann et al., H. H. Short-chain fatty acids: linking diet, the microbiome and immunity. Nat Rev Immunol 24, 577–595 (2024). https: / / doi.org / 10.1038 / s41577-024-01014-8, Nature Reviews Immunology), [nature.com]

[0391] The metabolic reprogramming of bone cells, particularly the shift toward glycolysis in osteoblasts, is influenced by SCFA signaling and is essential for the energy-intensive process of bone matrix production (Choi et al., one metabolism – an underappreciated player, npj Metab Health Dis 2, 12 (2024). https: / / doi.org / 10.1038 / s44324-024-00010-9, Nature).

[0392] [nature.com]

[0393] In early life, the establishment of the gut microbiota and the production of SCFAs are shaped by factors such as delivery mode, breastfeeding, and diet. Breastfed infants exhibit higher levels of SCFA-producing bacteria, including Bifidobacterium and Lactobacillus species, which contribute to elevated acetate levels in the gut. These microbial communities and their metabolic outputs are crucial during infancy, a period marked by rapid skeletal growth and mineralization. The temporal dynamics of SCFA production show a marked increase in acetate levels during the first two years of life, coinciding with critical windows of bone development (Mann et al., 2024). [nature.com]

[0394] Furthermore, SCFAs have been shown to influence the expression of genes involved in bone formation through epigenetic mechanisms. Acetate and other SCFAs can inhibit histone deacetylases (HDACs), leading to increased histone acetylation and the activation of osteogenic genes. This epigenetic modulation enhances the differentiation of mesenchymal stem cells into osteoblasts and supports the maintenance of bone homeostasis.

[0395] Collectively, these findings underscore the beneficial role of SCFAs, particularly acetate, in promoting bone growth and development. These effects are especially significant in infants and young children, where optimal bone accrual is essential for long-term skeletal health. Nutritional strategies that enhance SCFA production, such as the inclusion of fermentable fibers in the diet, may therefore represent a promising approach to support bone health from early life onward.

[0396] The mechanisms and evidence for SCFA-driven bone formation are described in Zulfiqar et al. (Animal Nutrition 22 (2025) 242–258). SCFA influence osteoblasts (bone-forming cells) and support bone homeostasis (page 247). Figure 3 visually summarizes the molecular pathways by which SCFAs, derived from dietary fiber, enhance osteoblast differentiation and function. Short-chain fatty acids, such as butyrate and propionate, enhance osteoblast differentiation and bone formation via GPR43-dependent activation of Wnt / β-catenin signaling, a critical pathway for osteoblastogenesis. Activation of GPR43 by SCFAs stabilizes β-catenin, promoting the expression of osteogenic genes like Runx2 and Osterix, while also suppressing sclerostin, a Wnt inhibitor, to amplify bone anabolism (page 251).

[0397] In a first aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one SCFA in the gastrointestinal tract of the subject.

[0398] In a further aspect, the invention provides the composition or combination of the invention for use in improving respiratory health, and / or gastrointestinal health in a subject by promoting the production of at least one SCFA in the gastrointestinal tract of the subject.

[0399] In a further aspect, the invention provides the use of a composition or combination according to the invention for use in promoting bone growth and / or bone development in a subject, by promoting the production of at least one SCFA in the gastrointestinal tract of the subject.

[0400] In a further aspect, the invention provides the use of a composition or combination according to the invention for use in promoting bone development, such as bone growth and / or bone strength and / or bone quality in a subject by promoting the production of at least one SCFA in the gastrointestinal tract of the subject.

[0401] Fatty acids and lipids

[0402] In some embodiments, the composition or combination of the invention promotes the production of at least one fatty acid or lipid in the gastrointestinal tract of a subject.

[0403] In a first aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one fatty acid or lipid in the gastrointestinal tract of the subject. In a further aspect, the invention provides the use of a composition or combination according to the invention for use in promoting bone growth and / or bone development in a subject, by promoting the production of at least one fatty acid or lipid in the gastrointestinal tract of the subject.

[0404] Urea

[0405] In some embodiments, the composition or combination of the invention promotes the production of at least one urea derivative or nitrogenous organic compound in the gastrointestinal tract of a subject.

[0406] Urea derivatives and nitrogenous organic compounds are responsible for maintaining nitrogen balance (e.g nitric oxide) and bioavailability (Nutrients. 2018 Jul 19; 10(7):921 ). Their benefits also include atherogenic-endothelial protection as well as anti-microbial properties (Nutrients.

[0407] 2018 Jul 19; 10(7):921 ).

[0408] In a first aspect, the present invention provides the composition or combination of the invention for use in therapy in a subject by promoting the production of at least one urea derivative or nitrogenous organic compound in the gastrointestinal tract of the subject.

[0409] In a further aspect, the invention provides the composition or combination of the invention for use in promoting bone growth and / or bone development in a subject by promoting the production of at least one urea derivative or nitrogenous organic compound in the gastrointestinal tract of the subject.

[0410] Bone growth / development

[0411] In a healthy subjects there are many conditions characterised by the need to increase bone formation. For example, in the case of bone fractures, it is necessary to stimulate bone growth in order to accelerate complete repair of the bone.

[0412] Although there exists to-day a large variety of active compounds for stimulating bone formation, there is a constant need for new active compounds, in particular owing to the limited success of the current treatments. Furthermore, in view of the chronic character of some conditions caused by an imbalance in bone metabolism, there is a need for new active compounds which it will be possible to use in the long term in man and animals, and which are likely to be available in the form of a food additive, for example in the form of a nutritional composition.

[0413] Moreover, at an earlier stage, the growth and development of the human skeleton requires an adequate supply of many different nutritional factors. Classical nutrient deficiencies are associated with stunting (e.g. energy, protein, Zn), rickets (e.g. vitamin D) and other bone abnormalities (e.g. Cu, Zn, vitamin C). There is evidence to suggest that peak bone mass and later fracture risk are influenced by the pattern of growth and nutritional exposures in childhood. However, it is challenging to define dietary reference values using bone health as a criterion, and the question of what type of diet constitutes the best support for optimal bone growth and development remains open (see e.g. Prentice, A., et al., 2006. Proceedings of the Nutrition Society, 65(4), pp.348-360).

[0414] Several approaches may be taken to improve the intake of growth-limiting nutrients, including administration of micronutrient supplements, fortification of food with micronutrients or improved dietary intake. However, particularly in populations where dietary quality is poor, several micronutrient deficiencies can co-occur, in which case growth may be affected by more than one growth-limiting nutrient (see e.g. Rivera, J. A., et al., 2003. The Journal of nutrition, 133(11), pp.4010S-4020S).

[0415] Thus, there is a demand for new nutritional interventions to promoting bone growth, enhancing bone growth and / or bone strength and / or increasing bone strength, for example in young children suffering from stunted growth and / or faltering growth.

[0416] In one aspect, the invention provides the use of a composition or combination according to the invention for use in promoting bone growth and / or bone development in a subject, optionally wherein the composition or combination promotes the production of one or more of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject. Adenosine monophosphate (AMP) has been linked to increased weight gain, overall growth in formula-fed infants based on findings from several randomized clinical trials (Pediatrics. 2010 Oct; 126(4):e946-53 and Am J Clin Nutr. 2008 Jun;87(6):1785-92).

[0417] In a further aspect, the invention provides the use of a composition or combination comprising Bifidobacterium longum subsp. iuvenis, a HMO mixture, and arabinan for use in promoting bone growth and / or bone development in a subject, optionally wherein the composition or combination promotes the production of one or more of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0418] In a further aspect, the invention provides the use of a composition or combination comprising or consisting of Bifidobacterium longum subsp. iuvenis and arabinan for use in promoting bone growth and / or bone development in a subject, optionally wherein the composition or combination promotes the production of one or more of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject. In a further aspect, the invention provides the use of a composition or combination according to the invention for use in preventing and / or increasing bone strength in a subject, optionally wherein the composition or combination promotes the production of one or more of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0419] In a further aspect, the invention provides the use of a composition or combination comprising Bifidobacterium longum subsp. iuvenis, a HMO mixture, and arabinan for use in increasing bone strength in a subject, optionally wherein the composition or combination promotes the production of one or more of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0420] In a further aspect, the invention provides the use of a composition or combination comprising or consisting of Bifidobacterium longum subsp. iuvenis and arabinan for use in increasing bone strength in a subject, optionally wherein the composition or combination promotes the production of one or more of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0421] The composition or combination of the present invention may promote bone growth and / or strength. In a further aspect, the invention provides the use of a composition or combination according to the invention for use in promoting bone growth and / or strength in a subject, optionally wherein the composition or combination promotes the production of SCFA, vitamins and / or nucleotides, or derivatives thereof (such as AMP), in the gastrointestinal tract of the subject.

[0422] Within the context of the present invention, the term “promoting bone growth and / or bone strength, or increasing bone strength” may refer to, in particular, one or more of the following physiological processes: bone catch-up growth, bone mass acquisition, optimization of peak bone mass, promotion of bone formation, promotion of bone anabolism, promotion of bone mineralization, increase of bone mineral density and micro-architecture, modulation of bone biomechanical properties, and modulation the ratio of bone formation.

[0423] As used herein, “promoting bone growth and / or strength” may refer to the support of normal bone growth and / or strength, for example during childhood and adolescence. Supporting normal bone growth and / or strength may result in normal bone anatomy and physiology. Suitable methods and parameters to determine bone growth and bone strength will be known to the skilled person (see e.g. Donnelly, E., 2011. Clinical Orthopaedics and Related Research, 469(8), pp.2128-2138). Suitably, normal bone growth and / or strength may be determined using one or more bone parameter selected from: trabecular bone volume fraction (BV / TV), trabecular thickness (Tb. Th), bone mineral density (BMD), bone mineral content (BMC), cortical bone volume (Ct. BV), medio-lateral diameter, antero-posterior diameter, bone ultimate force (FMax), and bone stiffness. In some embodiments, normal bone growth and / or strength is determined using one or more bone parameter selected from: bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone volume fraction (BV / TV), and cortical bone volume (Ct. BV). Suitable methods to determine these parameters will be available to the skilled person.

[0424] In some embodiments, the combination or composition of the invention improves one or more bone parameter selected from: trabecular bone volume fraction (BV / TV), bone mineral density (BMD), bone mineral content (BMC), cortical bone volume (Ct. BV), medio-lateral diameter, antero-posterior diameter, bone ultimate force (FMax), and bone stiffness.

[0425] In some embodiments, the combination or composition of the invention improves one or more bone parameter selected from: bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone volume fraction (BV / TV) and / or cortical bone volume (Ct. BV).

[0426] In some embodiments, promoting bone growth and / or bone strength, or increasing bone strength comprises an improvement in one or more bone parameter selected from: trabecular bone volume fraction (BV / TV), bone mineral density (BMD), bone mineral content (BMC), cortical bone volume (Ct. BV), medio-lateral diameter, antero-posterior diameter, bone ultimate force (FMax), and bone stiffness.

[0427] In some embodiments, promoting bone growth and / or bone strength, or increasing bone strength comprises an improvement in one or more bone parameter selected from: bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone volume fraction (BV / TV) and / or cortical bone volume (Ct. BV).

[0428] In some preferred embodiments, bone development is bone growth and / or bone strength and / or bone quality.

[0429] In a further embodiment, the composition or combination of the invention improves bone mineral density (BMD) by at least or equal to 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3% or 5%.

[0430] In a preferred embodiment, composition or combination of the invention improves bone mineral density (BMD) by between 0.1% and 5%, between 0.2% and 3%, more preferably between 0.2% and 2%, and most preferably between 0.3% and 1%. In a further embodiment, composition or combination of the invention improves trabecular and cortical bone volume fraction and / or trabecular thickness (Tb. Th) by at least or equal to 1%, 2%, 3%, 4%, 5%, 7%, 10%, 15%, 23%, 25%, 28%, 30% 35%, 40%, 45% or 50%.

[0431] In a further embodiment, composition or combination of the invention improves trabecular bone volume fraction by at least or equal to 1%, 2%, 3%, 4%, 5%, 7%, 10%, 15%, 23%, 25%, 28%, 30% 35%, 40%, 45% or 50%.

[0432] In a further embodiment, composition or combination of the invention improves cortical bone volume by at least or equal to 1%, 2%, 3%, 4%, 5%, 7%, 10%, 15%, 23%, 25%, 28%, 30% 35%, 40%, 45% or 50%.

[0433] In a further embodiment, composition or combination of the invention improves trabecular thickness (Tb. Th) by at least or equal to 1%, 2%, 3%, 4%, 5%, 7%, 10%, 15%, 23%, 25%, 28%, 30% 35%, 40%, 45% or 50%.

[0434] In a preferred embodiment, composition or combination of the invention improves trabecular and cortical bone volume fraction and / or trabecular thickness (Tb. Th) by between 1% and 45%, more preferably between 2% and 40%, more preferably between 3% and 35%, and most preferably between 4% and 35%.

[0435] In a preferred embodiment, composition or combination of the invention improves trabecular bone volume fraction by between 1% and 45%, more preferably between 2% and 40%, more preferably between 3% and 35%, and most preferably between 4% and 35%.

[0436] In a preferred embodiment, composition or combination of the invention improves cortical bone volume by between 1% and 45%, more preferably between 2% and 40%, more preferably between 3% and 35%, and most preferably between 4% and 35%.

[0437] In a preferred embodiment, composition or combination of the invention improves trabecular thickness (Tb. Th) by between 1% and 45%, more preferably between 2% and 40%, more preferably between 3% and 35%, and most preferably between 4% and 35%.

[0438] The supply of the composition according to the invention to an animal organism induces simultaneously a stimulation of bone formation, the overall increase of bone mineralisation, and hence of the bone density, being the result of the induction of these two mechanisms.

[0439] In order to determine whether a subject presents a state of reduced bone mass and as a consequence requires a supply of the composition according to the present invention, the specialist skilled in the art will be able to refer in particular to the report of the World Health Organisation (WHO) of 1994 entitled " Assessment of fracture risk and its application to screening for post-menopausal osteoporosis" (WHO Technical Series-843).

[0440] A composition according to the invention is also designed for individuals presenting symptoms of bone deficit resulting from a fracture, an operation or also a dental disease.

[0441] As has already been mentioned above, many disorders linked to an imbalance of bone metabolism, such as osteoporosis, develop gradually over a long period of time and require chronic treatments. Their prevention or their treatment can hence be carried out by means of a regular supply of the composition according to the present invention, preferably in the form of a nutritional composition.

[0442] Similarly, a regular nutritional supply of the composition according to the present invention to the subjects, is such as to make possible the production of a high bone density and an elevated peak bone mass.

[0443] The composition or combination of the present invention may promote catch-up growth e.g. in subjects with stunted growth and / or faltering growth. In a further aspect, the invention provides the use of a composition or combination according to the invention for use in promoting catchup growth in a subject, optionally wherein the composition or combination promotes the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0444] As used herein, “catch-up growth” may refer to height velocity above the limits of normal for age for at least 1 year after a transient period of growth inhibition and may be complete or incomplete (see e.g. Wit, J. M. and Boersma, B., 2002. Journal of Pediatric Endocrinology and Metabolism, 15, pp.1229-1242). Suitable methods and parameters to determine catch-up growth will be known to the skilled person. Suitably, catch-up growth may be determined using height velocity or height standard deviation score (see e.g. Frongillo, E. A., Leroy, J. L. and Lapping, K., 2019. Advances in Nutrition, 10(3), pp.372-379 and Desmond, C. and Casale, D., 2017. PloS one, 12(12), p.e0189135).

[0445] In some embodiments, the catch-up growth is determined in absolute terms of linear growth (i.e. the height deficit from the healthy reference population mean is reduced). In some embodiments, the catch-up growth is determined in relative terms of linear growth (i.e. the height-for-age z-score is improved and / or passes the -2SD or -1SD cut-off points).

[0446] Non-therapeutic use In a further aspect, the invention provides use of the composition or combination of the invention to promote the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject.

[0447] In a further aspect, the invention provides a method of promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, the method comprising administering to the subject the composition or combination of the invention.

[0448] In some embodiments, the one or more beneficial metabolites are at least one amino acid, peptide or protein.

[0449] In some embodiments, the one or more beneficial metabolites are at least one vitamin.

[0450] In some embodiments, the one or more beneficial metabolites are at least one nucleotide and / or associated metabolites.

[0451] In some embodiments, the one or more beneficial metabolites are at least one bile acid. In some embodiments, the one or more beneficial metabolites are at least one neurotransmitter.

[0452] In some embodiments, the one or more beneficial metabolites are at least one SCFA.

[0453] In some embodiments, the composition or combination of the invention increases total SCFA production.

[0454] In some embodiments, the one or more beneficial metabolites are at least one fatty acid or lipid.

[0455] In some embodiments, the one or more beneficial metabolites are urea and / or nitrogenous organic compounds.

[0456] The use or method of the present invention may be referred to as a non-therapeutic use or method. In some embodiments, the subject is a healthy subject.

[0457] Subject

[0458] The subject is a juvenile mammal, an infant, a young child or a child. In some preferred embodiments, the composition according to the invention is for use in infants, young children or children.

[0459] In one embodiment, the subject is an infant. In one embodiment, the subject is a young child. In one embodiment, the subject is a child.

[0460] In some preferred embodiments, the composition or combination according to the invention is for use in infants or young children. It is particularly adapted for infants under 6 months of age. The composition or combination may be particularly useful for preterm infants and / or low or very low birth weight infants. In another particularly interesting embodiment, the composition or combination is used in infants delivered via Caesarean section. Antibiotic administration is a recommended medical practice for C-section birth in order to prevent infection. Such interventions are potent disruptors of microbial communities (the mother’s or the child’s) and C-section born infants may have a delayed and less optimal colonization of the large intestinal tract.

[0461] The infants, young children or children may be born term or preterm. In a particular embodiment, the composition or combination of the invention is for use in infants, young children or children that were born preterm. Preterm infants may be at increased risk of poor nutrient utilization, impaired lean body mass growth, and fat accumulation in the visceral area later in life. Thus, in one embodiment the composition or combination of the invention is for use in preterm infants.

[0462] In one embodiment, the subject is an infant or a young child that was born small for gestational age or low birth weight.

[0463] Infants or young children with low birth weight may or may not be preterm, and similarly, infants or young children who are small for gestational age may or may not be preterm.

[0464] The composition or combination of the present invention may also be used in an infant or a young child that was born by C-section or that was vaginally delivered.

[0465] All infants and young children can benefit from the invention as all of them are or can be, at a certain age, susceptible to acquiring an unbalanced intestinal / gut microbiota.

[0466] In some advantageous embodiments of the invention, the composition or combination is for use juvenile mammals, infants or young children having a fragile or unbalanced microbiota or dysbiosis of microbiota, such as preterm infants, infants born by Caesarean-section, infants born small for gestational age or with low birth weight, hospitalized infants / young children, infants / young children treated or having been treated by antibiotics, infants / young children sick at birth including necrotizing enterocolitis (NEC), and / or infants / young children suffering or having suffered from gut infection.

[0467] It is indeed foreseen that the composition or combination of the invention may be even more beneficial to infants born with possibly impaired gut microbiota or fragile infants / young children (such as prematurely born infants and / or infants born by C-section). It is also foreseen that the composition or combination of the invention may be even more beneficial to infants / young children exhibiting intestinal disorders (such as diarrhea, infections or colic), especially after birth, for example, during the first 4 weeks after birth.

[0468] In embodiments of the invention, the infants born prematurely or born by caesarean section or born small for gestational age or with low birth weight, or exhibiting unbalanced or abnormal gut microbiota or suffering or having suffered from gut infection, are targeted by the composition or combination of the present invention, and especially when the infants are 0-6 months of age. Without being bound by the theory, it is believed that younger infants benefit even more from the composition or combination of the invention, especially when the infants have (or are at risk of having) an unbalanced intestinal microbiota and / or have a fragile health condition (as exemplified by the conditions cited above).

[0469] The composition or combination can be administered (or given or fed) at an age and for a period that depends on the needs.

[0470] In one embodiment, the infants or young children are 0-36 months of age, such as 0-12 months or 0-6 months of age. It is foreseen that the composition or combination of the invention may be even more beneficial to infants just after birth (0-4 weeks or 0-8 weeks) as their intestinal tract may be more fragile.

[0471] The subject to be treated is preferably a human being, but the subject may also be a juvenile non-human mammal, such as a non-human mammal selected from the group consisting of pig, cow, horse, dog, cat, goat, sheep and rabbit.

[0472] In some embodiments, the juvenile mammal is a pet.

[0473] A pet may be a mammal such as dogs or cats, or rodents such as mice, rats, and guinea pigs, rabbits, etc. In some embodiments, the pet is a small dog breed.

[0474] The term “juvenile mammal” may refer to a non-human mammal that has not yet reached adulthood.

[0475] In some embodiments the composition or combination according to the invention can be for use before and / or during the weaning period. In some preferred embodiments the composition or combination according to the invention is for use in a subject at risk and / or in need. The subject at risk and / or in need may be bottle-fed and / or formula-fed. The subject at risk and / or in need may be born by C-section and / or preterm, and / or small for gestational age (SGA) and / or with a low, very low, or extremely low weight at birth (LWB, VLBW, or ELBW) and / or experienced intra-uterine growth retardation (IUGR), and / or was hospitalized the first days following birth and / or took antibiotic the first days following birth and / or was sick at birth including necrotizing enterocolitis (NEC), and / or has impaired microbiota and / or dysbiosis of microbiota.

[0476] In some preferred embodiments, the subject suffered from and / or is suffering from stunted growth and / or faltering growth.

[0477] In one embodiment the composition or combination of the invention is given to the subject as a supplementary composition to the mother's milk. In some embodiments the subject receives the mother's milk during at least the first 2 weeks, first 1, 2, 4, or 6 months. In one embodiment the composition or combination of the invention is given to the subject after such period of mother's nutrition, or is given together with such period of mother's milk nutrition. In another embodiment the composition or combination is given to the subject as the sole or primary nutritional composition during at least one period of time, e.g. after the 1st, 2ndor 4thmonth of life, during at least 1, 2, 4 or 6 months. In one embodiment the composition or combination of the invention is a complete nutritional composition (fulfilling all or most of the nutritional needs of the subject). In another embodiment the composition or combination of the invention is a supplement or a fortifier intended for example to supplement human milk or to supplement an infant formula or a follow- on formula.

[0478] Nutritional composition

[0479] In some embodiments, the composition or combination of the invention is in the form of a nutritional composition.

[0480] The nutritional composition according to the invention can be for example an infant formula, a starter infant formula, a follow-on or follow-up formula, a growing-up milk, a baby food, an infant cereal composition, a fortifier such as a human milk fortifier, a supplement such as a pediatric supplement, a pet food, or a pet food supplement. In some particular embodiments, the composition of the invention is an infant formula, a fortifier or a supplement that may be intended for the first 4 or 6 months of age. In a preferred embodiment the nutritional composition of the invention is an infant formula.

[0481] In some embodiments, the nutritional composition contains only intact proteins as protein sources. In some embodiments, the nutritional composition contains intact and hydrolysed proteins as protein sources.

[0482] In some other embodiments, the nutritional composition of the present invention is a fortifier. The fortifier can be a breast milk fortifier (e.g. a human milk fortifier) or a formula fortifier such as an infant formula fortifier or a follow-on / follow-up formula fortifier.

[0483] When the nutritional composition is a supplement, it can be provided in the form of unit doses. In such cases it is particularly useful to define the amount of oligosaccharides and probiotics in terms of daily dose to be administered to the subject.

[0484] When the nutritional composition is a supplement, it may comprise the Bifidobacterium longum subsp. iuvenis and the HMO mixture as described herein, and no other additional nutrient on top of the excipients necessary to obtain a stable nutritional composition.

[0485] The nutritional composition of the present invention can be in solid (e.g. powder), liquid or gelatinous form. In a specific embodiment the nutritional composition is a supplement, wherein the supplement is in powder form and provided in a sachet, preferably a sachet with 0.1 to 20 g per sachet, for example 1 to 10 g per sachet, or in the form of a syrup, preferably a syrup with a total solid concentration of 5 to 75 g / 100 mL (5 to 75% (w / v)). When the supplement is in powder form, it may comprise a carrier. It is however preferred that the supplement is devoid of a carrier. When the supplement is in the form of a syrup, the components are preferably dissolved or suspended in water acidified with citrate.

[0486] When the nutritional composition is a supplement, it can be free of protein.

[0487] In a particular embodiment the nutritional composition according to the invention is a hypoallergenic composition. In another particular embodiment the composition according to the invention is a hypoallergenic nutritional composition.

[0488] Other ingredients

[0489] The composition or combination according to the present invention may also comprise any other suitable ingredients.

[0490] Suitably, the composition or combination according to the present invention may also comprise other types of oligosaccharide(s), polysaccharides and / or a fiber(s) and / or a precursor(s) thereof. The other oligosaccharide and / or fiber and / or precursor thereof may be selected from the list comprising human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS), xylooligosaccharides (XOS), cello-oligosaccharides (COS), arabinoxylans, arabinans, xylans, inulin, polydextrose, beta-glucans, pectins and any combination thereof and any derived preparations thereof (e.g. partial hydrolysis). They may be in an amount between 0 and 10% by weight of composition. In a particular embodiment, the nutritional composition or combination can also contain at least one BMO (bovine milk derived oligosaccharide).

[0491] Additional HMOs which may be included in the nutritional composition or combination according to the present invention may be selected from the group consisting of lacto-N-fucopentaose (e.g. lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V), lacto-N-fucohexaose, lacto-N-difucohexaose I, fucosyllacto-N-hexaose, fucosyllacto-N-neohexaose, difucosyllacto-N-hexaose I, difucosyllacto-N-neohexaose II, para-lacto-N-neohexaose (para-LNnH), lacto-N-hexaose, lacto- N-neohexaose, para-lacto-N-hexaose, para-lacto-N-neohexaose, lacto-N-octaose, lacto-N-neooctaose, iso-lacto-N-octaose, para-lacto-N-octaose, lacto-N-decaose, and any combination thereof.

[0492] In some embodiments, the composition or combination according to the invention comprises at least one additional HMO.

[0493] In other embodiments, the composition or combination according to the present invention is devoid of any further HMOs. Thus, the HMO mixture as described herein may be the only HMOs in the composition or combination of the invention.

[0494] In some embodiments, the composition or combination of the present invention does not comprise at least one further probiotic (or probiotic strain), such as at least one further probiotic bacterial strain.

[0495] In other embodiments, the composition or combination of the present invention can further comprise at least one further probiotic (or probiotic strain), such as at least one further probiotic bacterial strain.

[0496] The probiotic microorganisms most commonly used are principally bacteria and yeasts of the following genera: Lactobacillus spp., Lacticaseibacillus spp, Limosilactobacillus spp, Streptococcus spp., Enterococcus spp., Bifidobacterium spp. and Saccharomyces spp. In some particular embodiments, the probiotic is a probiotic bacterial strain. In some specific embodiments, it is particularly Bifidobacteria and / or Lactobacilli.

[0497] Suitable probiotic bacterial strains according to the present invention include B. longum CNCM 1-2618 (B. longum NCC2705), Bifidobacterium breve sold by Danisco under the trademark Bb-03, Bifidobacterium breve sold by Morinaga under the trade mark M-16V, Bifidobacterium breve sold by Morinaga under the trade mark B-3, Bifidobacterium breve sold by sold by Yakult under the trade mark BBG-01, Bifidobacterium breve sold by Institut Rosell (Lallemand) under the trademark R0070, Lactobacillus rhamnosus ATCC 53103 available from Valio Oy of Finland under the trademark LGG, Lactobacillus rhamnosus CGMCC 1.3724 deposited in October 2004 by Nestle R& D Centre Shanghai Ltd (13 Qiao Nan, Cao An Road, Jiading District, Shanghai 201812, P. R. China) according to the Budapest Treaty with China General Microbiological Culture Collection (CGMCC; Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100 101), Lactobacillus paracasei CNCM 1-2116 deposited on 12 January 1999 by SOCIETE DES PRODUITS NESTLE S. A according to the Budapest Treaty with the Collection nationale de cultures de micro-organisms (CNCM), Institute Pasteur (INSTITUT PASTEUR, 25 RUE DU DOCTEUR ROUX, F-75724 PARIS CEDEX 15, FRANCE) under the deposit number CNCM 1-2116, Lactobacillus johnsonii CNCM 1-1225, Streptococcus salivarius DSM 13084 sold by BLIS Technologies Limited of New Zealand under the designation KI2.

[0498] In some embodiments, the composition or combination of the invention comprises Lactobacillus paracasei CNCM 1-2116 or a strain having an Average Nucleotide Identity (ANI) of at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% to Lactobacillus paracasei CNCM 1-2116.

[0499] In some embodiments, the composition or combination of the invention comprises Lactobacillus rhamnosus CGMCC 1.3724 or a strain having an Average Nucleotide Identity (ANI) of at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9% to Lactobacillus rhamnosus CGMCC 1.3724.

[0500] The composition or combination according to the invention may contain from 10e3 to 10e12 cfu of the at least one (further) probiotic strain, more preferably from 10e7 to 10e12 cfu such as from 10e8 to 10e10 cfu of probiotic strain per g of composition or combination on a dry weight basis.

[0501] In one embodiment, the probiotics are viable. In another embodiment, the probiotics are nonreplicating or inactivated. There may be both viable probiotics and inactivated probiotics in some other embodiments. Probiotic components and metabolites can also be added.

[0502] The nutritional composition or combination according to the invention generally contains a protein source. The protein can be in an amount of from 1.6 to 3 g per 100 kcal. In some embodiments, especially when the composition is intended for premature infants, the protein amount can be between 2.4 and 4 g / 100kcal or more than 3.6 g / 100kcal (or 3.6 g / 100kcal or more). In some other embodiments the protein amount can be below 2.0 g per 100 kcal, e.g. between 1.8 to 2 g / 100 kcal, or in an amount below 1.8 g per 100 kcal.

[0503] Protein sources based on whey, casein and mixtures thereof may be used as well as protein sources based on soy. As far as whey proteins are concerned, the protein source may be based on acid whey or sweet whey or mixtures thereof and may include alpha-lactalbumin and beta-lactoglobulin in any desired proportions.

[0504] In some advantageous embodiments the protein source is whey predominant (i.e. more than 50% of proteins are coming from whey proteins, such as 51, 60% or 70%).

[0505] The proteins may be intact or hydrolysed or a mixture of intact and hydrolysed proteins. By the term “intact” is meant that the main part of the proteins are intact, i.e. the molecular structure is not altered, for example at least 80% of the proteins are not altered, such as at least 85% of the proteins are not altered, preferably at least 90% of the proteins are not altered, even more preferably at least 95% of the proteins are not altered, such as at least 98% of the proteins are not altered. In a particular embodiment, 100% of the proteins are not altered. The term “hydrolysed” means in the context of the present invention a protein which has been hydrolysed or broken down into its component amino acids. The proteins may be either fully or partially hydrolysed. It may be desirable to supply partially hydrolysed proteins (degree of hydrolysis between 2 and 20%), for example for infants or young children believed to be at risk of developing cow’s milk allergy. If hydrolysed proteins are required, the hydrolysis process may be carried out as desired and as is known in the art. For example, whey protein hydrolysates may be prepared by enzymatically hydrolysing the whey fraction in one or more steps. If the whey fraction used as the starting material is substantially lactose free, it is found that the protein suffers much less lysine blockage during the hydrolysis process. This enables the extent of lysine blockage to be reduced from about 15% by weight of total lysine to less than about 10% (or to about 10% or less) by weight of lysine; for example about 7% by weight of lysine which greatly improves the nutritional quality of the protein source.

[0506] In an embodiment of the invention at least 70% of the proteins are hydrolysed, preferably at least 80% of the proteins are hydrolysed, such as at least 85% of the proteins are hydrolysed, even more preferably at least 90% of the proteins are hydrolysed, such as at least 95% of the proteins are hydrolysed, particularly at least 98% of the proteins are hydrolysed. In a particular embodiment, 100% of the proteins are hydrolysed.

[0507] In one particular embodiment the proteins of the nutritional composition are hydrolyzed, fully hydrolyzed or partially hydrolyzed. The degree of hydrolysis (DH) of the protein can be between 8 and 40, or between 20 and 60 or between 20 and 80 or more than 10, 20, 40, 60, 80 or 90 (or 10, 20, 40, 60, 80 or 90 or more).

[0508] The protein component can alternatively be replaced by a mixture or synthetic amino acid, for example for preterm or low birth weight infants.

[0509] In a particular embodiment, the nutritional composition, the combination or the growing-up milk according to the invention is a hypoallergenic composition. In another particular embodiment, the composition or combination according to the invention is a hypoallergenic nutritional composition or growing-up milk.

[0510] The nutritional composition according to the present invention generally contains a carbohydrate source. This is particularly preferable in the case where the nutritional composition or combination of the invention is an infant formula. In this case, any carbohydrate source conventionally found in infant formulae such as lactose, sucrose, saccharose, maltodextrin, starch and mixtures thereof may be used although one of the preferred sources of carbohydrates is lactose.

[0511] The nutritional composition according to the present invention generally contains a source of lipids. This is particularly relevant if the nutritional composition of the invention is an infant formula. In this case, the lipid source may be any lipid or fat which is suitable for use in infant formulae. Some suitable fat sources include palm oil, structured triglyceride oil, high oleic sunflower oil and high oleic safflower oil, medium-chain-triglyceride oil. The essential fatty acids linoleic and a-linolenic acid may also be added, as well small amounts of oils containing high quantities of preformed arachidonic acid and docosahexaenoic acid such as fish oils or microbial oils. The fat source may have a ratio of n-6 to n-3 fatty acids of about 5:1 to about 15: 1; for example about 8: 1 to about 10: 1.

[0512] The nutritional composition of the invention may also contain all vitamins and minerals understood to be essential in the daily diet and in nutritionally significant amounts. Minimum requirements have been established for certain vitamins and minerals. Examples of minerals, vitamins and other nutrients optionally present in the composition of the invention include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum, taurine, and L-carnitine. Minerals are usually added in salt form. The presence and amounts of specific minerals and other vitamins will vary depending on the intended population. If necessary, the nutritional composition of the invention may contain emulsifiers and stabilisers such as soy, lecithin, citric acid esters of mono- and di-glycerides, and the like. The nutritional composition of the invention may also contain other substances which may have a beneficial effect such as nucleotides, nucleosides, and the like.

[0513] The nutritional composition of the invention may also contain carotenoid(s). In some particular embodiments of the invention, the nutritional composition of the invention does not comprise any carotenoid.

[0514] Thus, in preferred embodiments, the current invention is a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in therapy, or a nutritional composition comprising Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in therapy, wherein the HMO mixture consists of:

[0515] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0516] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL),

[0517] wherein the therapy is promoting bone growth and / or bone development or increasing bone strength in a subject, optionally wherein the combination or nutritional composition promotes the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0518] In some jurisdictions, the uses according to the invention are deemend non-therapeutic. Thus, in preferred embodiments, the current invention is a non-therapeutical use of a combination of Bifidobacterium longum subsp. iuvenis and of a HMO mixture, or of a nutritional composition comprising Bifidobacterium longum subsp. iuvenis and a HMO mixture, wherein the HMO mixture consists of:

[0519] lacto-N-fucopentaose I (LNFP-I), 2'-fucosy I lactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0520] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL),

[0521] wherein non-therapeutical use is promoting bone growth and / or bone development or increasing bone strength in a subject, optionally wherein the combination or nutritional composition promotes the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject.

[0522] Manufacture of a nutritional composition

[0523] The nutritional composition or combination according to the invention may be prepared in any suitable manner. A composition will now be described by way of example.

[0524] For example, a formula such as an infant formula may be prepared by blending together the protein source, the carbohydrate source and the fat source in appropriate proportions. If used, the emulsifiers may be included at this point. The vitamins and minerals may be added at this point but they are usually added later to avoid thermal degradation. Any lipophilic vitamins, emulsifiers and the like may be dissolved into the fat source prior to blending. Water, preferably water which has been subjected to reverse osmosis, may then be mixed in to form a liquid mixture. The temperature of the water is conveniently in the range between about 50°C and about 80°C to aid dispersal of the ingredients. Commercially available liquefiers may be used to form the liquid mixture.

[0525] The oligosaccharide(s) may be added at this stage, especially if the final product is to have a liquid form. If the final product is to be a powder, they may likewise be added at this stage if desired.

[0526] The liquid mixture is then homogenised, for example in two stages.

[0527] The liquid mixture may then be thermally treated to reduce bacterial loads, by rapidly heating the liquid mixture to a temperature in the range between about 80°C and about 150°C for a duration between about 5 seconds and about 5 minutes, for example. This may be carried out by means of steam injection, an autoclave or a heat exchanger, for example a plate heat exchanger.

[0528] Then, the liquid mixture may be cooled to between about 60°C and about 85°C for example by flash cooling. The liquid mixture may then be again homogenised, for example in two stages between about 10 MPa and about 30 MPa in the first stage and between about 2 MPa and about 10 MPa in the second stage. The homogenised mixture may then be further cooled to add any heat sensitive components, such as vitamins and minerals. The pH and solids content of the homogenised mixture are conveniently adjusted at this point.

[0529] If the final product is to be a powder, the homogenised mixture is transferred to a suitable drying apparatus such as a spray dryer or freeze dryer and converted to powder. The powder should have a moisture content of less than about 5% (or about 5% or less) by weight. The oligosaccharide(s) may also or alternatively be added at this stage by dry-mixing or by blending them in a syrup form of crystals, along with the probiotic strain(s), and the mixture is spray-dried or freeze-dried.

[0530] If a liquid composition is preferred, the homogenised mixture may be sterilised then aseptically filled into suitable containers or may be first filled into the containers and then retorted.

[0531] In another embodiment, the composition of the invention may be a supplement such as a pediatric supplement. The supplement may be in the form of tablets, capsules, pastilles or a liquid for example. The supplement may further contain protective hydrocolloids (such as gums, proteins, modified starches), binders, film forming agents, encapsulating agents / materials, wall / shell materials, matrix compounds, coatings, emulsifiers, surface active agents, solubilizing agents (oils, fats, waxes, lecithins etc.), adsorbents, carriers, fillers, cocompounds, dispersing agents, wetting agents, processing aids (solvents), flowing agents, taste masking agents, weighting agents, jellifying agents and gel forming agents. The supplement may also contain conventional pharmaceutical additives and adjuvants, excipients and diluents, including, but not limited to, water, gelatine of any origin, vegetable gums, lignin-sulfonate, talc, sugars, starch, gum arabic, vegetable oils, polyalkylene glycols, flavouring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like.

[0532] Further, the supplement may contain an organic or inorganic carrier material suitable for oral or parenteral administration as well as vitamins, minerals trace elements and other micronutrients in accordance with the recommendations of Government bodies such as the USRDA.

[0533] This disclosure is not limited by the exemplary methods and materials disclosed herein, and any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of this disclosure. Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated, any nucleic acid sequences are written left to right in 5' to 3' orientation; amino acid sequences are written left to right in amino to carboxy orientation, respectively.

[0534] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within this disclosure. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within this disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in this disclosure.

[0535] It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0536] The terms "comprising", "comprises" and "comprised of' as used herein are synonymous with "including", "includes" or "containing", "contains", and are inclusive or open-ended and do not exclude additional, non-recited members, elements or method steps. The terms "comprising", "comprises" and "comprised of' also include the term "consisting of.

[0537] The practice of the present invention will employ, unless otherwise indicated, conventional techniques of chemistry, biochemistry, molecular biology, microbiology and immunology, which are within the capabilities of a person of ordinary skill in the art. Such techniques are explained in the literature. See, for example, Sambrook, J., Fritsch, E. F. and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory Press; Ausubel, F. M. et al. (1995 and periodic supplements) Current Protocols in Molecular Biology, Ch. 9, 13 and 16, John Wiley & Sons; Roe, B., Crabtree, J. and Kahn, A. (1996) DNA Isolation and Sequencing: Essential Techniques, John Wiley & Sons; Polak, J. M. and McGee, J. O’D. (1990) In Situ Hybridization: Principles and Practice, Oxford University Press; Gait, M. J. (1984) Oligonucleotide Synthesis: A Practical Approach, IRL Press; and Lilley, D. M. and Dahlberg, J. E. (1992) Methods in Enzymology: DNA Structures Part A: Synthesis and Physical Analysis of DNA, Academic Press. Each of these general texts is herein incorporated by reference.

[0538] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that such publications constitute prior art to the claims appended hereto.

[0539] The invention will now be further described by way of Examples, which are meant to serve to assist one of ordinary skill in the art in carrying out the invention and are not intended in any way to limit the scope of the invention.

[0540] EXAMPLES

[0541] Example 1 - Bifidobacterium iuvenis synergistically produces beneficial metabolites when combined with a blend of 7 HMOs, including LNFP-I This study was conducted with microbiota colonic incubations as described in Front Microbiol.

[0542] 2023 Apr 14;14:1131662.

[0543] 8 arms were used in the study. These consisted of:

[0544] 1. HMO blend

[0545] 2. HMO blend + B. infantis

[0546] 3. HMO blend + B. iuvenis

[0547] 4. HMO blend + B. infantis + B. iuvenis

[0548] 5. HMO blend + LNFP-I

[0549] 6. HMO blend + B. infantis + LNFP-I

[0550] 7. HMO blend + B. iuvenis + LNFP-I

[0551] 8. HMO blend + B. infantis + B. iuvenis + LNFP-I

[0552] Each arm consisted of one bioreactor (n = 1) seeded with the pooled faecal microbiota of 6 individual donors. Donors were 3-month-old infants (± 3 weeks) exclusively fed with formulae without HMO / probiotics. The exclusion criteria were antibiotic use in 30 days before sample delivery for the study and previous NEC or gut surgery. This resulted in the enrolment of 6 specific test subjects with an average age of 3.0 (± 0.5) months. Intestinal absorption and colonic incubation conditions were then conducted (cf. Front Microbiol. 2023 Apr 14;14:1131662).

[0553] A blend of 6 HMOs was added at a final concentration of 5 g / L. The g / L composition of individual HMOs is described in the table below.

[0554] HMO Amount (g / L)

[0555] 2FL 2.46

[0556] 3FL 0.68

[0557] DFL 0.34

[0558] 3SL 0.31

[0559] 6SL 0.40

[0560] LNT 0.82

[0561] Total 5.00

[0562]

[0563] LNFP-I, when included, was dosed at a concentration 0.85 g / L in addition to the HMO blend. B. infantis LMG11588 and B. iuvenis CNCM I-5942 were each dosed at a concentration of 5 x 107CFU / mL, whether individually, or in combination.

[0564] Colonic incubations were carried out for 24 hours, with sampling at 0 and 24 hours for:

[0565] • SCFA levels by HPLC

[0566] The properties of the combination of the (potential) probiotics B. infantis and / or B. iuvenis, with or without the prebiotic HMO LNFP-I, and a background blend of other HMOs (including 2’FL, 3FL, Di FL, 3’SL, 6’SL and LNT) were explored in an ex vivo fecal fermentation study using the SIFR® technology. SIFR® technology mimics the proximal colonic environment and colonic fermentation process (Cryptobiotix, Ghent, Belgium). Fecal inocula were derived from six 3-month-old infants, which were exclusively fed with formulae without HMO nor probiotics. The exclusion criteria were antibiotic use in 30 days before sample delivery for the study and previous necrotizing enterocolitis or gut surgery. The six fecal inocula were pooled and homogenized prior to preparation of each bioreactor. Bioreactors were inoculated with combinations and controls consisting of the HMO blend including above mentioned HMOs as a background, B. infantis, B. iuvenis and LNFP-I. As outcomes, growth parameters, SCFA production, microbiome and metabolome composition were assessed. As the HMO blend was present as a background in all conditions, this study design allowed to quantify the incremental effect of LNFP-I and its potential synergy with B. infantis and / or B. iuvenis.

[0567] Acetate, butyrate, propionate, and total short chain fatty acid concentrations were quantified in liquid after 0 and 24 h incubation as described in Front Microbiol. 2023 Apr 14; 14: 1131662. A 6-HMO blend was present as background in all conditions. All possible combinations of the probiotic B. infantis LMG 11588 (5 x 107CFU / mL) and potential probiotic B. iuvenis CNCM I-5942 (5 x 107CFU / mL) supplementation were implemented (- / -, - / B. iuvenis, B. infantis I -, B. infantis I B. iuvenis). Additionally, for all those conditions, we implemented versions with and without LNFP-I supplementation at 0.85 g / L, (No, Yes). This thus resulted in 8 unique conditions in total. We show the production for each short chain fatty acid from 0 to 24 h. In all probiotic supplementation conditions and for all measured outcomes, LNFP-I addition results in higher concentrations after 24 h (see Figure 1 A and B). This shows an increase for LNFP-I on top of a 6-HMO blend for these health beneficial molecules. In some cases, the highest concentrations were achieved when both B. infantis LMG 11588 and B. iuvenis were simultaneously present. This shows the increase that can result from (potential) probiotic supplementation. Example 2 - Bifidobacterium iuvenis synergistically produces beneficial metabolites when combined with a blend of HMOs, including LNFP-I

[0568] An ex vivo fecal fermentation study was conducted with Cryptobiotix SA, using their proprietary ex-vivo human Gastrointestinal Tract replica model and microbiota colonic incubations as described in Front Microbiol. 2023 Apr 14; 14: 1131662.

[0569] Twenty-two arms were used in the study. These consisted of:

[0570] 1. Blank

[0571] 2. B. iuvenis

[0572] 3. LNFP-I

[0573] 4. HMO Blend I

[0574] 5. HMO Blend II

[0575] 6. HMO Blend I + LNFP-I

[0576] 7. HMO Blend II + LNFP-I

[0577] 8. LNFP-I + B. iuvenis

[0578] 9. HMO Blend I + B. iuvenis

[0579] 10. HMO Blend II + B. iuvenis

[0580] 11. HMO Blend I + LNFP-I + B. iuvenis

[0581] 12. HMO Blend II + LNFP-I + B. iuvenis

[0582] 13. LNFP-I + B. infantis

[0583] 14. HMO Blend I + B. infantis

[0584] 15. HMO Blend II + B. infantis

[0585] 16. HMO Blend I + LNFP-I + B. infantis

[0586] 17. HMO Blend II + LNFP-I + B. infantis

[0587] 18. LNFP-I + B. iuvenis + B. infantis

[0588] 19. HMO Blend I + B. iuvenis + B. infantis

[0589] 20. HMO Blend II + B. iuvenis + B. infantis

[0590] 21. HMO Blend I + LNFP-I + B. iuvenis + B. infantis

[0591] 22. HMO Blend II + LNFP-I + B. iuvenis + B. infantis

[0592] The HMO blends used in the study were as follows:

[0593] HMO blend I: 2FL, 3FL, DFL, 3SL, 6SL, LNT

[0594] HMO Blend II: 2FL, 3FL, DFL, 3SL, 6SL, LNT, LNnT

[0595] Suitable amounts for the HMO blends are as follows:

[0596] HMO Blend I: 49% 2FL, 14% 3FL, 7% DFL, 6% 3SL, 8% 6SL, and 16% LNT HMO Blend II: 38% 2FL, 14% 3FL, 5% DFL, 4% 3SL, 7% 6SL, 13% LNT, and 19% LNnT

[0597] A suitable dose for the carbohydrate LNFP-I is a concentration of 0.30 g / L, while the HMO blend may suitably be dosed at a final concentration of 2.66g / L.

[0598] Suitably, B. infantis LMG11588 and B. iuvenis CNCM I-5942 may be each dosed at a concentration of 5 x 107CFU / mL, whether individually, or in combination.

[0599] Each arm consisted of 8-12 bioreactors (n = 8 for 3 month old infants and n = 12 for 6 and 12 month old infants) seeded with the fecal microbiota of 8-12 individual donors. The same fecal inoculum of the donors was used for all arms. Donors were either 3-month-old infants (± 2 weeks) exclusively fed with formulae without HMO / probiotics. 12 donors of 6 and 12 months (± 2 weeks) were utilized to mimic the later timepoints. The exclusion criteria were antibiotic use in 30 days before sample delivery for the study and previous NEC or gut surgery. Intestinal absorption and colonic incubation conditions were then conducted using Cryptobiotix’s proprietary “ex-vivo SIFR” protocols (cf. Front Microbiol. 2023 Apr 14;14:1131662).

[0600] Colonic incubations were carried out for 48-hours, with sampling at 0, 24 and 48 hours for:

[0601] • SCFA analysis

[0602] • Metabolite analysis by LC-MS

[0603] LC-MS analysis was carried out using a Thermo Scientific Vanquish LC coupled to Thermo Q Exactive HF MS. An electrospray ionization interface was used as ionization source. Analysis was performed in negative and positive ionization mode. The UPLC was performed using a slightly modified version of the protocol described by Doneanu et al. (Anal Chem, 2015, 87, 10283-10291). Peak areas were extracted using Compound Discoverer 3.1 (Thermo Scientific). In addition to the automatic compound extraction by Compound Discoverer 3.1, a manual extraction of compounds included in an in-house library was performed using Skyline 21.1 (MacCoss Lab Software).

[0604] Example 3 - Bifidobacterium iuvenis synergistically produces beneficial metabolites when combined with a blend of HMOs, including LNFP-I

[0605] As above in example 2, with the following modifications.

[0606] Design:

[0607] 1. Blank

[0608] 2. B. iuvenis 3. B. infantis

[0609] 4. B. iuvenis + B. infantis

[0610] 5. LNFP-I

[0611] 6. HMO Blend I

[0612] 7. HMO Blend II

[0613] 8. HMO Blend I + LNFP-I

[0614] 9. HMO Blend II + LNFP-I

[0615] 10. LNFP-I + B. iuvenis

[0616] 11. HMO Blend I + B. iuvenis

[0617] 12. HMO Blend II + B. iuvenis

[0618] 13. HMO Blend I + LNFP-I + B. iuvenis

[0619] 14. HMO Blend II + LNFP-I + B. iuvenis

[0620] 15. LNFP-I + B. infantis

[0621] 16. HMO Blend I + B. infantis

[0622] 17. HMO Blend II + B. infantis

[0623] 18. HMO Blend I + LNFP-I + B. infantis

[0624] 19. HMO Blend II + LNFP-I + B. infantis

[0625] 20. LNFP-I + B. iuvenis + B. infantis

[0626] 21. HMO Blend I + B. iuvenis + B. infantis

[0627] 22. HMO Blend II + B. iuvenis + B. infantis

[0628] 23. HMO Blend I + LNFP-I + B. iuvenis + B. infantis

[0629] 24. HMO Blend II + LNFP-I + B. iuvenis + 8. infantis

[0630] Each arm consisted of 8 bioreactors seeded with the fecal microbiota of 8 individual donors. The same fecal inoculum of the donors was used for all arms. Donors were 3-month-old infants (± 2 weeks) exclusively fed with formulae without HMO / probiotics. The exclusion criteria were antibiotic use in 30 days before sample delivery for the study and previous NEC or gut surgery. Intestinal absorption and colonic incubation conditions were then conducted using Cryptobiotix’s proprietary “ex-vivo SIFR” protocols (cf. Front Microbiol. 2023 Apr 14;14:1131662).

[0631] Doses:

[0632] A blend of 6 or 7 HMOs was added at a final concentration of 2.5 g / L. The g / L composition of individual HMOs is described in the tables below.

[0633] HMO in HMO Blend I Amount (g / L)

[0634] 2FL 1.23

[0635] 3FL 0.34

[0636] DFL 0.17

[0637] 3SL 0.15

[0638] 6SL 0.20

[0639] LNT 0.41

[0640] Total 2.5

[0641] HMO HMO Blend II Amount (g / L)

[0642] 2FL 0.95

[0643] 3FL 0.37

[0644] DFL 0.11

[0645] 3SL 0.10

[0646] 6SL 0.17

[0647] LNT 0.33

[0648] LNnT 0.47

[0649] Total 2.5 HMO in HMO Blend I Amount (g / L)

[0650] 2FL 1.23

[0651] 3FL 0.34

[0652] DFL 0.17

[0653] 3SL 0.15

[0654] 6SL 0.20

[0655] LNT 0.41

[0656] Total 2.5

[0657] HMO in HMO Blend II Amount (g / L)

[0658] 2FL 0.95

[0659] 3FL 0.37

[0660] DFL 0.11

[0661] 3SL 0.10

[0662] 6SL 0.17

[0663] LNT 0.33

[0664] LNnT 0.47

[0665] Total 2.5

[0666] LNFP-I, when included, was dosed at a concentration 0.42 g / L in addition to the first HMO blend (HMO Blend I) and at a concentration 0.28 g / L in addition to the second HMO blend HMO Blend II.

[0667] B. infantis LMG11588 and B. iuvenis CNCM I-5942 were each dosed at a concentration of 2 x 107CFU / mL, whether individually, or in combination.

[0668] Colonic incubations were carried out for 48-hours, with sampling at 0, 24 and 48 hours for:

[0669] • SCFA analysis (acetate and total SCFA)

[0670] • pH (acidification)

[0671] In all cases, the HMO mix with additional LNFP-I result in larger final acetate (Figure 2) and final total SCFA increases compared to the same HMO mix without LNFP-I. The total amount of LNFP-I is too small to explain the acetate increase by total substrate only. In all cases, the HMO mix with additional LNFP-I result in larger final acidification compared to the same HMO mix without LNFP-I. The total amount of LNFP-I is too small to explain the acetate increase by total substrate only. EMBODIMENTS

[0672] Various preferred features and embodiments of the present invention will now be described with reference to the following numbered clauses:

[0673] 1. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in therapy, wherein the HMO mixture consists of:

[0674] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0675] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0676] 2. The combination for use according to clause 1, wherein the combination is for use in therapy by promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject.

[0677] 3. The combination for use according to clause 1 or clause 2, wherein the combination is for use in therapy by promoting the production of SCFA or derivatives thereof, in the gastrointestinal tract of a subject.

[0678] 4. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject (such as an infant or young child), wherein the HMO mixture consists of:

[0679] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0680] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL),

[0681] wherein the subject (such as the infant or young child) was born by C-section and / or preterm, and / or small for gestational age (SGA) and / or with a low, very low, or extremely low weight at birth (LWB, VLBW, or ELBW) and / or experienced intra-uterine growth retardation (IUGR), and / or was hospitalized the first days following birth and / or took antibiotic the first days following birth and / or was sick at birth, and / or has impaired microbiota and / or dysbiosis of microbiota.

[0682] 5. Use of a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture to promote the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, wherein the HMO mixture consists of:

[0683] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0684] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0685] 6. The combination for use according to any one of clauses 1-4, or the use according to clause 5, wherein the combination is administered separately, simultaneously or sequentially, preferably wherein the combination is administered simultaneously.

[0686] 7. The combination for use according to any of clauses 1-4 or 6, or the use according to clause 5 or 6, wherein the combination is provided in the form of a nutritional composition, preferably wherein the nutritional composition is selected from an infant formula, a starter infant formula, a follow-on or follow-up formula, a baby food, an infant cereal composition, a growing-up-milk, a fortifier such as a human milk fortifier, a supplement such as a pediatric supplement, a pet food, or a pet food supplement.

[0687] 8. The combination for use according to any of clauses 1-4 or 6-7, or the use according to any of clauses 5-7, wherein the Bifidobacterium longum subsp. iuvenisis capable of metabolizing one or more of the HMO(s).

[0688] 9. The combination for use according to clause 8, or the use according to clause 8, wherein the Bifidobacterium longum subsp. iuvenis is capable of metabolizing all of the HMOs.

[0689] 10. The combination for use according to any of clauses 1-4 or 6-9, or the use according to any of clauses 5-9, wherein the Bifidobacterium longum subsp. iuvenis preferentially utilizes 3-FL over 2’-FL.

[0690] 11. The combination for use according to any of clauses 1 -4 or 6-10, or the use according to any of clauses 5-10, wherein the Bifidobacterium longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98% with at least one Bifidobacterium longum strain selected in the group consisting of CNCM I-5942, CNCM I-5683, CNCM I-5684, CNCM I-5685, CNCM I-5686, CNCM I-5687, CMCC-P0001 (ATCC BAA-2753), and any combination thereof.

[0691] 12. The combination for use according to any of clauses 1-4 or 6-11, or the use according to any of clauses 5-11, wherein the Bifidobacterium longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98% with at least one Bifidobacterium longum subsp. iuvenis strain selected in the group consisting of CNCM I-5942, CNCM I-5683, CNCM I-5684, CNCM I-5685, CNCM I-5686, CNCM I-5687, and any combination thereof.

[0692] 13. The combination for use according to any of clauses 1-4 or 6-12, or the use according to any of clauses 5-12, wherein the Bifidobacterium longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98%, preferably at least 99%, with the Bifidobacterium longum subsp. iuvenis strain deposited with the CNCM under deposit number CNCM I-5942.

[0693] 14. The combination for use according to any of clauses 1-4, 6-10 or 13, or the use according to any of clauses 5-11 or 13, wherein the Bifidobacterium longum subsp. iuvenis is not resistant to any one of tetracycline and erythromycin.

[0694] 15. The combination for use according to any of clauses 1-4, 6-10 or 13-14, or the use according to any of clauses 5-11 or 13-14, wherein the Bifidobacterium longum subsp. iuvenis is not resistant to any one of tetracycline, erythromycin, clindamycin and ampicillin.

[0695] 16. The combination for use according to any of clauses 1-4, 6-10 or 13-15, or the use according to any of clauses 5-15, wherein the Bifidobacterium longum subsp. iuvenis is not resistant to any of tetracycline, erythromycin, clindamycin, ampicillin, gentamycin, streptomycin, chloramphenicol and vancomycin.

[0696] 17. The combination for use according to any of clauses 14-16, or the use according to any of clauses 14-16, wherein:

[0697] (a) lack of resistance to tetracycline is due to absence of a tetracycline resistance gene, suitably a tetW gene which encodes a protein with at least 80% sequence identity to SEQ ID NO: 1 and / or a tetQ which encodes a protein with at least 80% sequence identity to SEQ ID NO: 2;

[0698] (b) lack of resistance to erythromycin is due to absence of a erythromycin resistance gene, suitably a Erm49 gene which encodes a protein with at least 80% sequence identity to SEQ ID NO: 3;

[0699] (c) lack of resistance to erythromycin and / or clindamycin is due to absence of a corresponding resistance gene, suitably a Erm(X) gene which encodes a protein with at least 80% sequence identity to SEQ ID NO: 4; and / or (d) lack of resistance to chloramphenicol is due to absence of a chloramphenicol resistance gene, suitably a CrmX gene which encodes a protein with at least 80% sequence identity to SEQ ID NO: 6.

[0700] 18. The combination for use according to any of clauses 1 -4 or 6-17, or the use according to any of clauses 5-17, wherein the Bifidobacterium longum subsp. iuvenis comprises a glycosyl hydrolase family 43_17 (GH43_17) gene; suitably wherein the GH43_17 gene comprises SEQ ID NO: 7 or a sequence with at least 60% sequence identity to SEQ ID NO: 7.

[0701] 19. The combination for use according to any of clauses 1 -4 or 6-18, or the use according to any of clauses 5-18, wherein the Bifidobacterium longum subsp. iuvenis further comprises a major facilitator superfamily (MFS) gene; suitably wherein the MFS gene comprises SEQ ID NO: 37 or a sequence with at least 60% sequence identity to SEQ ID NO: 37.

[0702] 20. The combination for use according to any of clauses 1 -4 or 6-19, or the use according to any of clauses 5-19, wherein the Bifidobacterium longum subsp. iuvenis further comprises an AraC gene; suitably wherein the AraC gene comprises SEQ ID NO: 39 or a sequence with at least 60% sequence identity to SEQ ID NO: 39.

[0703] 21. The combination for use according clause 20, or the use according to clause 20, wherein the GH43_17, MFS and AraC genes are comprised in a gene cluster.

[0704] 22. The combination for use according to any of clauses 18-21, or the use according to any of clauses 18-21, wherein the Bifidobacterium longum subsp. iuvenis further comprises one or more of a GH31 gene, and a Lacl gene; preferably further comprising a xylulose kinase gene and a xylose isomerase gene.

[0705] 23. The combination for use according clause 22, or the use according to clause 22, wherein the GH43_17, MFS, AraC, GH31, and Lacl genes are comprised in a gene cluster; preferably wherein the GH43_17, MFS, AraC, GH31, Lacl, xylulose kinase and xylose isomerase genes are comprised in a gene cluster.

[0706] 24. The combination for use according to any of clauses 1-4 or 6-23, or the use according to any of clauses 5-23, wherein the Bifidobacterium longum subsp. iuvenis further comprises one or more genes encoding for one or more glycoside hydrolases selected from GH43_17, GH43_22, GH43_27, GH43_29, GH121, GH43_24, GH127, GH30_5, GH 43_32 and GH30. 25. The combination for use according to any of clauses 1-4 or 6-24, or the use according to any of clauses 5-24, wherein the Bifidobacterium longum subsp. iuvenis further comprises GH29 and GH95 genes.

[0707] 26. The combination for use according to any of clauses 1-4 or 6-25, or the use according to any of clauses 5-25, wherein the Bifidobacterium longum subsp. iuvenis preferentially utilizes 3-fucosyllactose (3-FL).

[0708] 27. The combination for use according to any of clauses 1-4 or 6-26, or the use according to any of clauses 5-26, wherein the Bifidobacterium longum subsp. iuvenis has a growth rate of at least 0.6 k when cultured in the presence of 3-FL.

[0709] 28. The combination for use according to any of clauses 1-4 or 6-27, or the use according to any of clauses 5-27, wherein the combination comprises from 103to 1012cfu of Bifidobacterium longum subsp. iuvenis, preferably from 107to 1012cfu of Bifidobacterium longum subsp. iuvenis, more preferably from 108to 1010cfu of Bifidobacterium longum subsp. iuvenis per g of combination or composition on a dry weight basis.

[0710] 29. The combination for use according to any of clauses 1-4 or 6-28, or the use according to any of clauses 5-28, wherein the combination further comprises at least one further probiotic selected from Bifidobacterium longum subsp. infantis, Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei, and Lactobacillus rhamnosus.

[0711] 30. The combination for use according to clause 29, or the use according to clause 29, wherein:

[0712] (a) the Bifidobacterium longum subsp. infantis is Bifidobacterium longum subsp. infantis LMG 11588 or a strain having an Average Nucleotide Identity (ANI) of at least 95%, preferably at least 99%, more preferably at least 99.9% to Bifidobacterium longum subsp. infantis LMG 11588;

[0713] (b) the Bifidobacterium animalis subsp. lactis is Bifidobacterium animalis subsp. lactis CNCM I-3446 or a strain having an Average Nucleotide Identity (ANI) of at least 95%, preferably at least 99%, more preferably at least 99.9% to Bifidobacterium animalis subsp. lactis CNCM I-3446;

[0714] (c) the Lactobacillus paracasei is Lactobacillus paracasei ST11 (also known as CNCM I- 2116) or a strain having an Average Nucleotide Identity (ANI) of at least 95%, preferably at least 99%, more preferably at least 99.9% Lactobacillus paracasei ST11 (also known as CNCM I-2116); and / or (d) the Lactobacillus rhamnosus is Lactobacillus rhamnosus CGMCC 1.3724 or a strain having an Average Nucleotide Identity (ANI) of at least 95%, preferably at least 99%, more preferably at least 99.9% to Lactobacillus rhamnosus CGMCC 1.3724.

[0715] 31a. The combination for use according to clause 29 or clause 30, or the use according to clause 29 or clause 30, wherein the composition comprises from 103to 1012cfu of Bifidobacterium longum subsp. infantis, Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei, and / or Lactobacillus rhamnosus, preferably from 107to 1012cfu of Bifidobacterium longum subsp. infantis, Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei, and / or Lactobacillus rhamnosus, more preferably from 108to 1010cfu of Bifidobacterium longum subsp. infantis, Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei, and / or Lactobacillus rhamnosus per g of composition on a dry weight basis.

[0716] 31b. The combination for use according to any of clauses 1, 2 or 4-31 a, or the use according to any of clauses 3-31 a, wherein the combination further comprises Bifidobacterium longum subsp. lactis and Bifidobacterium longum subsp. infantis.

[0717] 32. The combination for use according to any of clauses 1-4 or 6-31 a-b, or the use according to any of clauses 5-31 a-b, wherein the combination comprises LNFP-I in a total amount of from 25 mg / L to 4000 mg / L of the combination or composition or from 0.02 g / 100 g to 3.75 g / 100 g of the combination or composition on a dry weight basis.

[0718] 33. The combination for use according to any of clauses 1-4 or 6-32, or the use according to any of clauses 5-32, wherein the combination comprises LNFP-I in a total amount of from 50 mg / L to 2500 mg / L, preferably from 60 mg / L to 2000 mg / L, more preferably from 80 mg / L to 1500 mg / L of the combination or composition; or from 0.04 g / 100 g to 2 g / 100 g, preferably from 0.05 g / 100 g to 1.6 g / 100 g, more preferably from 0.06 g / 100 g to 1.2 g / 100 g, most preferably from 0.07 g / 100 g to 0.8 g / 100 g of the combination or composition on a dry weight basis.

[0719] 34. The combination for use according to any of clauses 1-4 or 6-33, or the use according to any of clauses 5-33, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL).

[0720] 35. The combination for use according to any of clauses 1-4 or 6-34, or the use according to any of clauses 5-34, wherein the HMO mixture consists of:

[0721] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), and 3-fucosyllactose (3FL); or LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0722] 36. The combination for use according to clause 35 or the use according to clause 35, wherein the HMO mixture consists essentially of:

[0723] i. 20 wt% to 46 wt% of 2FL, preferably 22 wt% to 42 wt% of 2FL;

[0724] ii. 11 wt% to 17 wt% of LNT, preferably 12 wt% to 15 wt% of LNT;

[0725] iii. 2 wt% to 7 wt% of DFL, preferably 3 wt% to 6 wt% of DFL;

[0726] iv. 9 wt% to 21 wt% of 6SL and 3SL combined, preferably 9 wt% to 19 wt% of 6SL and 3SL combined;

[0727] v. 9 wt% to 34 wt% of 3FL, preferably 11 wt% to 32 wt% of 3FL; and

[0728] vi. 5 wt% to 32 wt% of LNFP-I, preferably 10 wt% to 19 wt% of LNFP-I.

[0729] 37. The combination for use according to any of clauses 1-4 or 6-33, or the use according to any of clauses 5-33, wherein the HMO mixture consists of:

[0730] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), and lacto-N-neotetraose (LNnT); or

[0731] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0732] 38. The combination for use according to clause 37, or the use according to clause 37, wherein the HMO mixture consists essentially of:

[0733] i. 27 wt% to 41 wt% of 2FL, preferably 32 wt% to 39 wt%;

[0734] ii. 8 wt% to 15 wt% of LNT, preferably 10 wt% to 14 wt%;

[0735] iii. 4 wt% to 6 wt% of DFL, preferably 4 wt% to 6 wt%;

[0736] iv. 8 wt% to 18 wt% of 6SL and 3SL combined, preferably 7 wt% to 15 wt%;

[0737] v. 13 wt% to 21 wt% of LNnT, preferably 16 wt% to 20 wt%; and

[0738] vi. 7 wt% to 33 wt% of LNFP-I, preferably 11 wt% to 23 wt%.

[0739] 39. The combination for use according to any of clauses 1-4 or 6-33, or the use according to any of clauses 5-33, wherein the HMO mixture consists of:

[0740] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), 3-fucosyllactose (3FL), and lacto-N-neotetraose (LNnT); or

[0741] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL). 40. The combination for use according to clause 39, or the use according to clause 39, wherein the HMO mixture consists essentially of:

[0742] i. 29 wt% to 40 wt% of 2FL, preferably 32 wt% to 39 wt% of 2FL;

[0743] ii. 8 wt% to 13 wt% of LNT, preferably 9 wt% to 12 wt% of LNT;

[0744] iii. 3 wt% to 11 wt % of DFL;

[0745] iv. 3 wt% to 15 wt% of 6SL and 3SL combined, preferably 4 wt% to 15 wt% of 6SL and 3SL combined;

[0746] v. 11 wt% to 35 wt% of 3FL, preferably 12 wt% to 35 wt% of 3FL;

[0747] vi. 1 wt% to 18 wt% of LNnT, preferably 1 wt% to 17 wt% of LNnT; and

[0748] vii. 2 wt% to 24 wt% of LNFP-I, preferably 4 wt% to 14 wt% of LNFP-I.

[0749] 41. The combination for use according to any of clauses 1-4 or 6-40, wherein the therapy is improving cardiovascular health or treating and / or preventing a cardiovascular disease in a subject, optionally wherein the combination promotes the production of nucleotides or derivatives thereof in the gastrointestinal tract of the subject.

[0750] 42. The combination for use according to any of clauses 1-4 or 6-40, wherein the therapy is improving neurological health, promoting brain growth and / or brain development, or treating and / or preventing a neurological disorder in a subject, optionally wherein the combination promotes the production of nucleotides and / or neurotransmitters, or derivatives thereof, in the gastrointestinal tract of the subject.

[0751] 43. The combination for use according to any of clauses 1-4 or 6-40, wherein the therapy is improving mental health or treating and / or preventing a mental disorder in a subject, optionally wherein the combination promotes the production of nucleotides and / or neurotransmitters, or derivatives thereof, in the gastrointestinal tract of the subject.

[0752] 44. The combination for use according to any of clauses 1-4 or 6-40, wherein the therapy is improving respiratory health or treating and / or preventing a respiratory disease in a subject, optionally wherein the combination promotes the production of amino acids, peptides, proteins, vitamins, nucleotides, bile acids, and / or SCFA, or derivatives thereof, in the gastrointestinal tract of the subject.

[0753] 45. The combination for use according to any of clauses 1-4 or 6-40, wherein the therapy is improving gastrointestinal health in a subject, optionally wherein the combination promotes the production of amino acids, peptides, proteins, vitamins, nucleotides, SCFA, urea, and / or nitrogenous organic compounds, or derivatives thereof, in the gastrointestinal tract of the subject. 46. The combination for use according to any of clauses 1-4 or 6-40, wherein the therapy is modulating the immune response in a subject, optionally wherein the combination promotes the production of amino acids, peptides, proteins, nucleotides, bile acids, and / or SCFA, or derivatives thereof, in the gastrointestinal tract of the subject.

[0754] 47. The combination for use according to any of clauses 1-4 or 6-40, wherein the therapy is preventing and / or treating an infection in a subject, optionally wherein the combination promotes the production of amino acids, peptides, proteins, vitamins, nucleotides, and / or SCFA, or derivatives thereof, in the gastrointestinal tract of the subject.

[0755] 48. The combination for use according to any of clauses 1-4 or 6-40, wherein the therapy is promoting bone growth and / or bone development or increasing bone strength in a subject (such as an infant or young child), optionally wherein the combination promotes the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject, preferably wherein the combination further comprises arabinan.

[0756] 49. The combination for use according to clause 48, wherein the subject (such as the infant or young child) suffered from and / or is suffering from stunted growth and / or faltering growth, optionally wherein bone growth and / or bone development or increasing bone strength comprises improving one or more bone parameter selected from: bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone volume fraction (BV / TV) and / or cortical bone volume (Ct. BV).

[0757] 50. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in improving cardiovascular health or treating and / or preventing a cardiovascular disease in a subject, optionally by promoting the production of nucleotides or derivatives thereof in the gastrointestinal tract of the subject, wherein the HMO mixture consists of:

[0758] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0759] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0760] 51. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in improving neurological health, promoting brain growth and / or brain development, or treating and / or preventing a neurological disorder in a subject, optionally by promoting the production of nucleotides and / or neurotransmitters, or derivatives thereof, in the gastrointestinal tract of the subject, wherein the HMO mixture consists of: lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0761] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0762] 52. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in improving mental health or treating and / or preventing a mental disorder in a subject, optionally by promoting the production of nucleotides and / or neurotransmitters, or derivatives thereof, in the gastrointestinal tract of the subject, wherein the HMO mixture consists of: lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0763] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0764] 53. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in improving respiratory health or treating and / or preventing a respiratory disease in a subject, optionally by promoting the production of amino acids, peptides, proteins, vitamins, nucleotides, bile acids, and / or SCFA, or derivatives thereof, in the gastrointestinal tract of the subject, wherein the HMO mixture consists of:

[0765] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0766] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0767] 54. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in improving gastrointestinal health in a subject, optionally by promoting the production of amino acids, peptides, proteins, vitamins, nucleotides, SCFA, urea, and / or nitrogenous organic compounds, or derivatives thereof, in the gastrointestinal tract of the subject, wherein the HMO mixture consists of:

[0768] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0769] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL). 55. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in modulating the immune response in a subject, optionally by promoting the production of amino acids, peptides, proteins, nucleotides, bile acids, and / or SCFAs, or derivatives thereof, in the gastrointestinal tract of the subject, wherein the HMO mixture consists of:

[0770] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0771] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0772] 56. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in preventing and / or treating an infection in a subject, optionally by promoting the production of amino acids, peptides, proteins, vitamins, nucleotides, and / or SCFA, or derivatives thereof, in the gastrointestinal tract of the subject, wherein the HMO mixture consists of:

[0773] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0774] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0775] 57. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in promoting bone growth and / or bone development or increasing bone strength in a subject (such as an infant or young child), optionally by promoting the production of SCFA, vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject, wherein the HMO mixture consists of:

[0776] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0777] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL),

[0778] preferably wherein the combination further comprises arabinan.

[0779] 58. The combination for use according to clause 57, wherein the subject (such as the infant or young child) suffered from and / or is suffering from stunted growth and / or faltering growth, optionally wherein bone growth and / or bone development or increasing bone strength comprises improving one or more bone parameter selected from: bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone volume fraction (BV / TV) and / or cortical bone volume (Ct. BV).

[0780] 59. The combination for use according to any of clauses 50-58, wherein the combination is defined according to any of clauses 6-40.

[0781] 60. A nutritional composition comprising Bifidobacterium longum subsp. iuvenis and a HMO mixture, wherein the HMO mixture consists of:

[0782] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0783] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0784] 61. The nutritional composition according to clause 60, wherein the nutritional composition is selected from an infant formula, a starter infant formula, a follow-on or follow-up formula, a baby food, an infant cereal composition, a growing-up-milk, a fortifier such as a human milk fortifier, a supplement such as a pediatric supplement, a pet food, or a pet food supplement.

[0785] 62. The nutritional composition according to clause 60 or clause 61, wherein the

[0786] 63. The nutritional composition according to clause 62, wherein the Bifidobacterium longum subsp. iuvenis is capable of metabolizing all of the HMO(s).

[0787] 64. The nutritional composition according to any one of clauses 60-63, wherein the Bifidobacterium longum subsp. iuvenis preferentially utilizes 3-FL over 2’-FL.

[0788] 65. The nutritional composition according to any one of clauses 60-64, wherein the Bifidobacterium longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98% with at least one Bifidobacterium longum strain selected in the group consisting of CNCM I-5942, CNCM I-5683, CNCM I-5684, CNCM I-5685, CNCM I-5686, CNCM I-5687, CMCC-P0001 (ATCC BAA-2753), and any combination thereof.

[0789] 66. The nutritional composition according to any one of clauses 60-65, wherein the Bifidobacterium longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98% with at least one Bifidobacterium longum subsp. iuvenis strain selected in the group consisting of CNCM I-5942, CNCM I-5683, CNCM I-5684, CNCM I-5685, CNCM I-5686, CNCM I-5687, and any combination thereof.

[0790] 67. The nutritional composition according to any one of clauses 60-66, wherein the Bifidobacterium longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98%, preferably at least 99%, with the Bifidobacterium longum subsp. iuvenis strain deposited with the CNCM under deposit number CNCM I-5942.

[0791] 68. The nutritional composition according to any one of clauses 60-64 or 67, wherein the Bifidobacterium longum subsp. iuvenis is not resistant to any one of tetracycline and erythromycin.

[0792] 69. The nutritional composition according to any one of clauses 60-64 or 67-68, wherein the Bifidobacterium longum subsp. iuvenis is not resistant to any one of tetracycline, erythromycin, clindamycin and ampicillin.

[0793] 70. The nutritional composition according to any one of clauses 60-64 or 67-69, wherein the Bifidobacterium longum subsp. iuvenis is not resistant to any of tetracycline, erythromycin, clindamycin, ampicillin, gentamycin, streptomycin, chloramphenicol and vancomycin.

[0794] 71. The nutritional composition according to any one of clauses 68-70, wherein:

[0795] (a) lack of resistance to tetracycline is due to absence of a tetracycline resistance gene, suitably a tetW gene which encodes a protein with at least 80% sequence identity to SEQ ID NO: 1 and / or a tetQ which encodes a protein with at least 80% sequence identity to SEQ ID NO: 2;

[0796] (b) lack of resistance to erythromycin is due to absence of a erythromycin resistance gene, suitably a Erm49 gene which encodes a protein with at least 80% sequence identity to SEQ ID NO: 3;

[0797] (c) lack of resistance to erythromycin and / or clindamycin is due to absence of a corresponding resistance gene, suitably a Erm(X) gene which encodes a protein with at least 80% sequence identity to SEQ ID NO: 4; and / or

[0798] (d) lack of resistance to chloramphenicol is due to absence of a chloramphenicol resistance gene, suitably a CrmX gene which encodes a protein with at least 80% sequence identity to SEQ ID NO: 6.

[0799] 72. The nutritional composition according to any one of clauses 60-71, wherein the Bifidobacterium longum subsp. iuvenis comprises a glycosyl hydrolase family 43_17 (GH43_17) gene; suitably wherein the GH43_17 gene comprises SEQ ID NO: 7 ora sequence with at least 60% sequence identity to SEQ ID NO: 7.

[0800] 73. The nutritional composition according to any one of clauses 60-72, wherein the Bifidobacterium longum subsp. iuvenis further comprises a major facilitator superfamily (MFS) gene; suitably wherein the MFS gene comprises SEQ ID NO: 37 or a sequence with at least 60% sequence identity to SEQ ID NO: 37. 74. The nutritional composition according to any one of clauses 60-73, wherein the Bifidobacterium longum subsp. iuvenis further comprises an AraC gene; suitably wherein the AraC gene comprises SEQ ID NO: 39 or a sequence with at least 60% sequence identity to SEQ ID NO: 39.

[0801] 75. The nutritional composition according to clause 74, wherein the GH43_17, MFS and AraC genes are comprised in a gene cluster.

[0802] 76. The nutritional composition according to any one of clauses 72-75, wherein the Bifidobacterium longum subsp. iuvenis further comprises one or more of a GH31 gene, and a Lacl gene; preferably further comprising a xylulose kinase gene and a xylose isomerase gene.

[0803] 77. The nutritional composition according to clause 76, wherein the GH43_17, MFS, AraC, GH31, and Lacl genes are comprised in a gene cluster; preferably wherein the GH43_17, MFS, AraC, GH31, Lacl, xylulose kinase and xylose isomerase genes are comprised in a gene cluster.

[0804] 78. The nutritional composition according to any one of clauses 60-77, wherein the Bifidobacterium longum subsp. iuvenis further comprises one or more genes encoding for one or more glycoside hydrolases selected from GH43_17, GH43_22, GH43_27, GH43_29, GH121, GH43_24, GH127, GH30_5, GH 43_32 and GH30.

[0805] 79. The nutritional composition according to any one of clauses 60-78, wherein the Bifidobacterium longum subsp. iuvenis further comprises GH29 and GH95 genes.

[0806] 80. The nutritional composition according to any one of clauses 60-79, wherein the Bifidobacterium longum subsp. iuvenis preferentially utilizes 3-fucosyllactose (3-FL).

[0807] 81. The nutritional composition according to any one of clauses 60-80, wherein the Bifidobacterium longum subsp. iuvenis has a growth rate of at least 0.6 k when cultured in the presence of 3-FL.

[0808] 82. The nutritional composition according to any one of clauses 60-81, wherein the combination comprises from 103to 1012cfu of Bifidobacterium longum subsp. iuvenis, preferably from 107to 1012cfu of Bifidobacterium longum subsp. iuvenis, more preferably from 108to 1010cfu of Bifidobacterium longum subsp. iuvenis per g of combination or composition on a dry weight basis.

[0809] 83. The nutritional composition according to any one of clauses 60-82, wherein the compositon further comprises at least one further probiotic selected from Bifidobacterium longum subsp. infantis, Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei, and Lactobacillus rhamnosus.

[0810] 84. The nutritional composition according to clause 83, wherein:

[0811] (a) the Bifidobacterium longum subsp. infantis is Bifidobacterium longum subsp. infantis LMG 11588 or a strain having an Average Nucleotide Identity (ANI) of at least 95%, preferably at least 99%, more preferably at least 99.9% to Bifidobacterium longum subsp. infantis LMG 11588;

[0812] (b) the Bifidobacterium animalis subsp. lactis is Bifidobacterium animalis subsp. lactis CNCM I-3446 or a strain having an Average Nucleotide Identity (ANI) of at least 95%, preferably at least 99%, more preferably at least 99.9% to Bifidobacterium animalis subsp. lactis CNCM I-3446;

[0813] (c) the Lactobacillus paracasei is Lactobacillus paracasei ST11 (also known as CNCM I- 2116) or a strain having an Average Nucleotide Identity (ANI) of at least 95%, preferably at least 99%, more preferably at least 99.9% to Lactobacillus paracasei ST11 (also known as CNCM I-2116); and / or

[0814] (d) the Lactobacillus rhamnosus is Lactobacillus rhamnosus CGMCC 1.3724 or a strain having an Average Nucleotide Identity (ANI) of at least 95%, preferably at least 99%, more preferably at least 99.9% to Lactobacillus rhamnosus CGMCC 1.3724.

[0815] 85a. The nutritional composition according to clause 83 or clause 84, wherein the composition comprises from 103to 1012cfu of Bifidobacterium longum subsp. infantis, Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei, and / or Lactobacillus rhamnosus, preferably from 107to 1012cfu of Bifidobacterium longum subsp. infantis, Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei, and / or Lactobacillus rhamnosus, more preferably from 108to 1010cfu of Bifidobacterium longum subsp. infantis, Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei, and / or Lactobacillus rhamnosus per g of composition on a dry weight basis.

[0816] 85b. The nutritional composition according to any one of clauses 60-85a, wherein the combination further comprises Bifidobacterium longum subsp. lactis and Bifidobacterium longum subsp. infantis.

[0817] 86. The nutritional composition according to any one of clauses 60-85a-b, wherein the nutritional composition comprises LNFP-I in a total amount of from 25 mg / L to 4000 mg / L of the composition or from 0.02 g / 100 g to 3.75 g / 100 g of the composition on a dry weight basis.

[0818] 87. The nutritional composition according to any one of clauses 60-86, wherein the nutritional composition comprises LNFP-I in a total amount of from 50 mg / L to 2500 mg / L, preferably from 60 mg / L to 2000 mg / L, more preferably from 80 mg / L to 1500 mg / L of the composition; or from 0.04 g / 100 g to 2 g / 100 g, preferably from 0.05 g / 100 g to 1.6 g / 100 g, more preferably from 0.06 g / 100 g to 1.2 g / 100 g, most preferably from 0.07 g / 100 g to 0.8 g / 100 g of the composition on a dry weight basis.

[0819] 88. The nutritional composition according to any one of clauses 60-87, wherein the HMO mixture consists of:

[0820] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL); or

[0821] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0822] 89. The nutritional composition according to any one of clauses 60-87, wherein the HMO mixture consists of:

[0823] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), and 3-fucosyllactose (3FL); or

[0824] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0825] 90. The nutritional composition according to clause 89, wherein the HMO mixture consists essentially of:

[0826] i. 20 wt% to 46 wt% of 2FL, preferably 22 wt% to 42 wt% of 2FL;

[0827] ii. 11 wt% to 17 wt% of LNT, preferably 12 wt% to 15 wt% of LNT;

[0828] iii. 2 wt% to 7 wt% of DFL, preferably 3 wt% to 6 wt% of DFL;

[0829] iv. 9 wt% to 21 wt% of 6SL and 3SL combined, preferably 9 wt% to 19 wt% of 6SL and 3SL combined;

[0830] v. 9 wt% to 34 wt% of 3FL, preferably 11 wt% to 32 wt% of 3FL; and

[0831] vi. 5 wt% to 32 wt% of LNFP-I, preferably 10 wt% to 19 wt% of LNFP-I.

[0832] 91. The nutritional composition according to any one of clauses 60-87, wherein the HMO mixture consists of:

[0833] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), and lacto-N-neotetraose (LNnT); or

[0834] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL). 92. The nutritional composition according to clause 91, wherein the HMO mixture consists essentially of:

[0835] i. 27 wt% to 41 wt% of 2FL, preferably 32 wt% to 39 wt%;

[0836] ii. 8 wt% to 15 wt% of LNT, preferably 10 wt% to 14 wt%;

[0837] iii. 4 wt% to 6 wt% of DFL, preferably 4 wt% to 6 wt%;

[0838] iv. 8 wt% to 18 wt% of 6SL and 3SL combined, preferably 7 wt% to 15 wt%; v. 13 wt% to 21 wt% of LNnT, preferably 16 wt% to 20 wt%; and

[0839] vi. 7 wt% to 33 wt% of LNFP-I, preferably 11 wt% to 23 wt%.

[0840] 93. The nutritional composition according to any one of clauses 60-87, wherein the HMO mixture consists of:

[0841] lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), 3-fucosyllactose (3FL), and lacto-N-neotetraose (LNnT); or

[0842] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0843] 94. The nutritional composition according to clause 93, wherein the HMO mixture consists essentially of:

[0844] i. 29 wt% to 40 wt% of 2FL, preferably 32 wt% to 39 wt% of 2FL;

[0845] ii. 8 wt% to 13 wt% of LNT, preferably 9 wt% to 12 wt% of LNT;

[0846] iii. 3 wt% to 11 wt % of DFL;

[0847] iv. 3 wt% to 15 wt% of 6SL and 3SL combined, preferably 4 wt% to 15 wt% of 6SL and 3SL combined;

[0848] v. 11 wt% to 35 wt% of 3FL, preferably 12 wt% to 35 wt% of 3FL;

[0849] vi. 1 wt% to 18 wt% of LNnT, preferably 1 wt% to 17 wt% of LNnT; and

[0850] vii. 2 wt% to 24 wt% of LNFP-I, preferably 4 wt% to 14 wt% of LNFP-I.

[0851] 95. The nutritional composition according to any of clauses 60-94, for use in therapy in a subject.

[0852] 96. The nutritional composition according to any of clauses 60-95, for use in promoting bone growth and / or bone development and / or increasing bone strength in a subject.

[0853] 97. The nutritional composition according to any of clauses 60-95, for use in promoting bone growth and / or bone development in a subject.

[0854] 98. The nutritional composition according to any one of clauses 60-95, for use in promoting bone development, such as bone growth and / or bone strength and / or bone quality, in a subject (such as an infant or young child), optionally wherein the composition further comprises arabinan.

[0855] 99. The nutritional composition according to any one of clauses 60-95, for use in promoting bone development, such as bone growth and / or bone strength and / or bone quality in a subject (such as an infant or young child).

[0856] 100. The nutritional composition according to any one of clauses 95-99, wherein the composition further comprises arabinan.

[0857] 101. The nutritional composition for use according to clause 100, wherein the subject (such as the infant or young child) suffered from and / or is suffering from stunted growth and / or faltering growth, optionally wherein bone growth and / or bone development and / or increasing bone strength comprises improving one or more bone parameter selected from: bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone volume fraction (BV / TV) and / or cortical bone volume (Ct. BV).

[0858] 102. Use of the nutritional composition according to any of clauses 60-94, to promote the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject.

[0859] 103. The nutritional composition according to any of clauses 60-94 for use in promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, wherein the subject was born by C-section and / or preterm, and / or small for gestational age (SGA) and / or with a low, very low, or extremely low weight at birth (LWB, VLBW, or ELBW) and / or experienced intra-uterine growth retardation (IUGR), and / or was hospitalized the first days following birth and / or took antibiotic the first days following birth and / or was sick at birth, and / or has impaired microbiota and / or dysbiosis of microbiota.

[0860] 104. A method of promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, the method comprising administering the subject a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture, wherein the HMO mixture consists of: lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT); or

[0861] LNFP-I, 2'-fucosyllactose (2FL), and 3-fucosyllactose (3FL).

[0862] 105. The method according to clause 104, wherein the combination is defined according to any of clauses 6-40.

[0863] 106. The combinaison or nutritional composition according to any of the preceding clauses, comprising Bifidobacterium longum subsp. iuvenis CNCM I-5942 and the HMO mixture. 107. The combinaison or nutritional composition according to clause 106, wherein Bifidobacterium longum subsp. iuvenis CNCM I-5942 is the only probiotic present in the combinaison or nutritional composition.

[0864] 108. The combinaison or nutritional composition according to any of clauses 1-106, comprising Bifidobacterium longum subsp. iuvenis, Bifidobacterium longum subsp. infantis and the HMO mixture.

[0865] 109. The combinaison or nutritional composition according to clause 108, wherein Bifidobacterium longum subsp. iuvenis and Bifidobacterium longum subsp. infantis are the only probiotics present in the combinaison or nutritional composition.

[0866] 110. The combinaison or nutritional composition according to any of clauses 1-106, comprising Bifidobacterium longum subsp. iuvenis, Bifidobacterium animalis subsp. lactis and the HMO mixture.

[0867] 111. The combinaison or nutritional composition according to clause 110, wherein Bifidobacterium longum subsp. iuvenis and Bifidobacterium animalis subsp. lactis are the only probiotics present in the combinaison or nutritional composition.

[0868] 112. The combinaison or nutritional composition according to any of clauses 1-106, comprising Bifidobacterium longum subsp. iuvenis, Bifidobacterium longum subsp. infantis, Bifidobacterium animalis subsp. lactis and the HMO mixture.

[0869] 113. The combinaison or nutritional composition according to clause 112, wherein Bifidobacterium longum subsp. iuvenis, Bifidobacterium longum subsp. infantis and Bifidobacterium animalis subsp. lactis are the only probiotics present in the combinaison or nutritional composition. All publications mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described methods and system of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in molecular biology or related fields are intended to be within the scope of the following claims. (Original in Electronic Form)

[0870] (This sheet is not part of and does not count as a sheet of the international application) 0-1 Form PCT / RO / 134

[0871] Indications Relating to Deposited

[0872] Microorganism(s) or Other Biological

[0873] Material (PCT Rule 13bis)

[0874] 0-1-1 Prepared Using ePCT-Filing-Embedded

[0875] Version 4.15.022 MT / FOP 20251014 / 2.8

[0876] 0-2 International Application No.

[0877] 0-3 Applicant's or agent's file reference 19777-WO-PCT

[0878]

[0879] 1 The indications made below relate to

[0880] the deposited microorganism(s) or

[0881] other biological material referred to in

[0882] the description on:

[0883] 1-1 page 55

[0884] 1-2 line 16

[0885] 1-3 Identification of deposit

[0886] 1-3-1 Name of depositary institution CNCM Collection nationale de cultures de micro- organismes

[0887] 1-3-2 Address of depositary institution Collection nationale de cultures de micro- organismes (CNCM)

[0888] Institut Pasteur, 25-28

[0889] rue du Docteur Roux,

[0890] 75724 Paris Cedex 15

[0891] France

[0892] 1-3-3 Date of deposit 07 June 2005 (07.06.2005)

[0893] 1-3-4 Accession Number CNCM I-3446

[0894] 1-4 Additional Indications

[0895] 1-5 Designated States for Which All designations

[0896] Indications are Made

[0897] 1-6 Separate Furnishing of Indications NCC 2818

[0898] These indications will be submitted to the

[0899]

[0900] International Bureau later (Original in Electronic Form)

[0901] (This sheet is not part of and does not count as a sheet of the international application) 2 The indications made below relate to

[0902] the deposited microorganism(s) or

[0903] other biological material referred to in

[0904] the description on:

[0905] 2-1 page 5

[0906] 2-2 line 24

[0907] 2-3 Identification of deposit

[0908] 2-3-1 Name of depositary institution CNCM Collection nationale de cultures de micro- organismes

[0909] 2-3-2 Address of depositary institution Collection nationale de cultures de micro- organismes (CNCM)

[0910] Institut Pasteur, 25-28

[0911] rue du Docteur Roux,

[0912] 75724 Paris Cedex 15

[0913] France

[0914] 2-3-3 Date of deposit 11 May 2021 (11.05.2021)

[0915] 2-3-4 Accession Number CNCM 1-5683

[0916] 2-4 Additional Indications

[0917] 2-5 Designated States for Which All designations

[0918] Indications are Made

[0919] 2-6 Separate Furnishing of Indications NCC 5000

[0920] These indications will be submitted to the

[0921] International Bureau later

[0922] 3 The indications made below relate to

[0923] the deposited microorganism(s) or

[0924] other biological material referred to in

[0925] the description on:

[0926] 3-1 page 5

[0927] 3-2 line 24

[0928] 3-3 Identification of deposit

[0929] 3-3-1 Name of depositary institution CNCM Collection nationale de cultures de micro- organismes

[0930] 3-3-2 Address of depositary institution Collection nationale de cultures de micro- organismes (CNCM)

[0931] Institut Pasteur, 25-28

[0932] rue du Docteur Roux,

[0933] 75724 Paris Cedex 15

[0934] France

[0935] 3-3-3 Date of deposit 11 May 2021 (11.05.2021)

[0936] 3-3-4 Accession Number CNCM 1-5684

[0937] 3-4 Additional Indications

[0938] 3-5 Designated States for Which All designations

[0939] Indications are Made

[0940] 3-6 Separate Furnishing of Indications NCC 5001

[0941] These indications will be submitted to the

[0942]

[0943] International Bureau later (Original in Electronic Form)

[0944] (This sheet is not part of and does not count as a sheet of the international application) 4 The indications made below relate to

[0945] the deposited microorganism(s) or

[0946] other biological material referred to in

[0947] the description on:

[0948] 4-1 page 5

[0949] 4-2 line 24

[0950] 4-3 Identification of deposit

[0951] 4-3-1 Name of depositary institution CNCM Collection nationale de cultures de micro- organismes

[0952] 4-3-2 Address of depositary institution Collection nationale de cultures de micro- organismes (CNCM)

[0953] Institut Pasteur, 25-28

[0954] rue du Docteur Roux,

[0955] 75724 Paris Cedex 15

[0956] France

[0957] 4-3-3 Date of deposit 11 May 2021 (11.05.2021)

[0958] 4-3-4 Accession Number CNCM 1-5685

[0959] 4-4 Additional Indications

[0960] 4-5 Designated States for Which All designations

[0961] Indications are Made

[0962] 4-6 Separate Furnishing of Indications NCC 5002

[0963] These indications will be submitted to the

[0964] International Bureau later

[0965] 5 The indications made below relate to

[0966] the deposited microorganism(s) or

[0967] other biological material referred to in

[0968] the description on:

[0969] 5-1 page 5

[0970] 5-2 line 24

[0971] 5-3 Identification of deposit

[0972] 5-3-1 Name of depositary institution CNCM Collection nationale de cultures de micro- organismes

[0973] 5-3-2 Address of depositary institution Collection nationale de cultures de micro- organismes (CNCM)

[0974] Institut Pasteur, 25-28

[0975] rue du Docteur Roux,

[0976] 75724 Paris Cedex 15

[0977] France

[0978] 5-3-3 Date of deposit 11 May 2021 (11.05.2021)

[0979] 5-3-4 Accession Number CNCM 1-5686

[0980] 5-4 Additional Indications

[0981] 5-5 Designated States for Which All designations

[0982] Indications are Made

[0983] 5-6 Separate Furnishing of Indications NCC 5003

[0984] These indications will be submitted to the

[0985]

[0986] International Bureau later (Original in Electronic Form)

[0987] (This sheet is not part of and does not count as a sheet of the international application) 6 The indications made below relate to

[0988] the deposited microorganism(s) or

[0989] other biological material referred to in

[0990] the description on:

[0991] 6-1 page 5

[0992] 6-2 line 25

[0993] 6-3 Identification of deposit

[0994] 6-3-1 Name of depositary institution CNCM Collection nationale de cultures de micro- organismes

[0995] 6-3-2 Address of depositary institution Collection nationale de cultures de micro- organismes (CNCM)

[0996] Institut Pasteur, 25-28

[0997] rue du Docteur Roux,

[0998] 75724 Paris Cedex 15

[0999] France

[1000] 6-3-3 Date of deposit 11 May 2021 (11.05.2021)

[1001] 6-3-4 Accession Number CNCM 1-5687

[1002] 6-4 Additional Indications

[1003] 6-5 Designated States for Which All designations

[1004] Indications are Made

[1005] 6-6 Separate Furnishing of Indications NCC 5004

[1006] These indications will be submitted to the

[1007] International Bureau later

[1008] 7 The indications made below relate to

[1009] the deposited microorganism(s) or

[1010] other biological material referred to in

[1011] the description on:

[1012] 7-1 page 15

[1013] 7-2 line 28

[1014] 7-3 Identification of deposit

[1015] 7-3-1 Name of depositary institution CNCM Collection nationale de cultures de micro- organismes

[1016] 7-3-2 Address of depositary institution Collection nationale de cultures de micro- organismes (CNCM)

[1017] Institut Pasteur, 25-28

[1018] rue du Docteur Roux,

[1019] 75724 Paris Cedex 15

[1020] France

[1021] 7-3-3 Date of deposit 29 March 2023 (29.03.2023)

[1022] 7-3-4 Accession Number CNCM I-5942

[1023] 7-4 Additional Indications

[1024] 7-5 Designated States for Which All designations

[1025] Indications are Made

[1026] 7-6 Separate Furnishing of Indications NCC 5025

[1027] These indications will be submitted to the

[1028]

[1029] International Bureau later (Original in Electronic Form)

[1030] (This sheet is not part of and does not count as a sheet of the international application) 8 The indications made below relate to

[1031] the deposited microorganism(s) or

[1032] other biological material referred to in

[1033] the description on:

[1034] 8-1 page 74

[1035] 8-2 line 29

[1036] 8-3 Identification of deposit

[1037] 8-3-1 Name of depositary institution CNCM Collection nationale de cultures de micro- organismes

[1038] 8-3-2 Address of depositary institution Collection nationale de cultures de micro- organismes (CNCM)

[1039] Institut Pasteur, 25-28

[1040] rue du Docteur Roux,

[1041] 75724 Paris Cedex 15

[1042] France

[1043] 8-3-3 Date of deposit 29 January 2001 (29.01.2001)

[1044] 8-3-4 Accession Number CNCM 1-2618

[1045] 8-4 Additional Indications

[1046] 8-5 Designated States for Which All designations

[1047] Indications are Made

[1048] 8-6 Separate Furnishing of Indications NCC 2705

[1049] These indications will be submitted to the

[1050] International Bureau later

[1051] 9 The indications made below relate to

[1052] the deposited microorganism(s) or

[1053] other biological material referred to in

[1054] the description on:

[1055] 9-1 page 75

[1056] 9-2 line 7

[1057] 9-3 Identification of deposit

[1058] 9-3-1 Name of depositary institution CNCM Collection nationale de cultures de micro- organismes

[1059] 9-3-2 Address of depositary institution Collection nationale de cultures de micro- organismes (CNCM)

[1060] Institut Pasteur, 25-28

[1061] rue du Docteur Roux,

[1062] 75724 Paris Cedex 15

[1063] France

[1064] 9-3-3 Date of deposit 12 January 1999 (12.01.1999)

[1065] 9-3-4 Accession Number CNCM 1-2116

[1066] 9-4 Additional Indications

[1067] 9-5 Designated States for Which All designations

[1068] Indications are Made

[1069] 9-6 Separate Furnishing of Indications NCC 2461

[1070] These indications will be submitted to the

[1071]

[1072] International Bureau later (Original in Electronic Form)

[1073] (This sheet is not part of and does not count as a sheet of the international application) 10 The indications made below relate to

[1074] the deposited microorganism(s) or

[1075] other biological material referred to in

[1076] the description on:

[1077] 10-1 page 75

[1078] 10-2 line 11

[1079] 10-3 Identification of deposit

[1080] 10-3-1 Name of depositary institution CNCM Collection nationale de cultures de micro- organismes

[1081] 10-3-2 Address of depositary institution Collection nationale de cultures de micro- organismes (CNCM)

[1082] Institut Pasteur, 25-28

[1083] rue du Docteur Roux,

[1084] 75724 Paris Cedex 15

[1085] France

[1086] 10-3-3 Date of deposit 30 June 1992 (30.06.1992)

[1087] 10-3-4 Accession Number CNCM 1-1225

[1088] 10-4 Additional Indications

[1089] 10-5 Designated States for Which All designations

[1090] Indications are Made

[1091] 10-6 Separate Furnishing of Indications La 1

[1092] These indications will be submitted to the

[1093] Interna...

Claims

1. CLAIMS1. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in promoting bone growth and / or bone development in a subject, optionally wherein the combination promotes the production of one or more beneficial metabolites selected from short chain fatty acids (SCFA), vitamins and / or nucleotides, or derivatives thereof, in the gastrointestinal tract of the subject, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyl lactose (3FL) and / or lacto-N-neotetraose (LNnT).

2. The combination for use according to claim 1, wherein the combination is for use in promoting bone growth and / or bone development by promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject.

3. A combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture for use in promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyl lactose (3FL) and / or lacto-N-neotetraose (LNnT), wherein the subject was born by C-section and / or preterm, and / or small for gestational age (SGA) and / or with a low, very low, or extremely low weight at birth (LWB, VLBW, or ELBW) and / or experienced intra-uterine growth retardation (IUGR), and / or was hospitalized the first days following birth and / or took antibiotic the first days following birth and / or was sick at birth, and / or has impaired microbiota and / or dysbiosis of microbiota.

4. Use of a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture to promote the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose(LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyl lactose (3FL) and / or lacto-N-neotetraose (LNnT).

5. The combination for use according to any of claims 1-3, or the use according to claim 4, for promoting bone development, such as bone growth and / or bone strength and / or bone quality.

6. The combination for use according to any of claims 1-3 or 5, or the use according to claim 4 or 5, wherein the combination is provided in the form of a nutritional composition, preferably wherein the nutritional composition is selected from an infant formula, a starter infant formula, a follow-on or follow-up formula, a baby food, an infant cereal composition, a growing-up-milk, a fortifier such as a human milk fortifier, a supplement such as a pediatric supplement, a pet food, or a pet food supplement.

7. The combination for use according to any of claims 1-3 or 5-6, or the use according to claim 4-6, wherein the Bifidobacterium longum subsp. iuvenis:9.a) is capable of metabolizing one or more of the HMO(s), preferably all of the HMOs; b) preferentially utilizes 3-FL over 2’-FL; and / or10.c) is not resistant to any one of tetracycline, erythromycin, clindamycin and ampicillin, preferably wherein the Bifidobacterium longum subsp. iuvenis is not resistant to any of tetracycline, erythromycin, clindamycin, ampicillin, gentamycin, streptomycin, chloramphenicol and vancomycin.

8. The combination for use according to any of claims 1-3, 5-7, or the use according to any of claims 4-7, wherein the Bifidobacterium longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98% with at least one Bifidobacterium longum strain selected in the group consisting of CNCM I-5942, CNCM I-5683, CNCM I-5684, CNCM I-5685, CNCM I-5686, CNCM I-5687, CMCC-P0001 (ATCC BAA-2753), and any combination thereof, preferably wherein the Bifidobacterium longum subsp. iuvenis has an Average Nucleotide Identity (ANI) of at least 98%, preferably at least 99%, with the Bifidobacterium longum subsp. iuvenis strain deposited with the CNCM under deposit number CNCM I-5942.

9. The combination for use according to any of claims 1-3 or 5-8, or the use according to any of claims 4-8, wherein the combination comprises from 103to 1012cfu of Bifidobacterium longum subsp. iuvenis, preferably from 107to 1012cfu of Bifidobacterium longum subsp. iuvenis, more preferably from 108to 1010cfu of Bifidobacterium longum subsp. iuvenis per g of combination or composition on a dry weight basis.

10. The combination for use according to any of claims 1-3 or 5-9, or the use according to any of claims 4-9, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), and 3-fucosyl lactose (3FL).

11. The combination for use according to any of claims 1-3 or 5-9, or the use according to any of claims 4-9, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), and lacto-N-neotetraose (LNnT).

12. The combination for use according to any of claims 1-3 or 5-9, or the use according to any of claims 4-9, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), 3-fucosyl lactose (3FL), and lacto-N-neotetraose (LNnT).

13. The combination for use according to any of claims 1-3 or 5-12, wherein promoting bone growth and / or bone strength and / or bone quality.

14. A nutritional composition comprising Bifidobacterium longum subsp. iuvenis and a HMO mixture, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT), preferably wherein the nutritional composition is selected from an infant formula, a starter infant formula, a follow-on or follow-up formula, a baby food, an infant cereal composition, a growing-up-milk, a fortifier such as a human milk fortifier, a supplement such as a pediatric supplement, a pet food, or a pet food supplement.

15. Use of the nutritional composition according to claim 14 to promote the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject.

16. The nutritional composition according to claim 14 for use in promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, wherein the subject was born by C-section and / or preterm, and / or small for gestational age (SGA) and / or with a low, very low, or extremely low weight at birth (LWB, VLBW, or ELBW) and / or experienced intra-uterine growth retardation (IUGR), and / or washospitalized the first days following birth and / or took antibiotic the first days following birth and / or was sick at birth, has impaired microbiota and / or dysbiosis of microbiota, and / or suffered from and / or is suffering from stunted growth and / or faltering growth.

17. A method of promoting the production of one or more beneficial metabolites selected from amino acids, peptides, proteins, vitamins, nucleotides, bile acids, neurotransmitters, short chain fatty acids (SCFA), fatty acids, lipids, urea, nitrogenous organic compounds, and derivatives thereof, in the gastrointestinal tract of a subject, the method comprising administering the subject a combination of Bifidobacterium longum subsp. iuvenis and a HMO mixture, wherein the HMO mixture consists of lacto-N-fucopentaose I (LNFP-I), 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), and 3'-sialyllactose (3SL), and optionally 3-fucosyllactose (3FL) and / or lacto-N-neotetraose (LNnT).

18. The combination for use, the nutritional composition for use, the use, or the method according to any of the proceeding claims, wherein the combination or nutritional composition is further comprising Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis.

19. The combination for use according to any one of claim 1 to 3, nutritional composition for use according to claim 16, the use according to claim 4 or 15, or the method of claim 17, wherein the beneficial metabolites are short chain fatty acids (SCFA), vitamins and / or nucleotides, or derivatives thereof.

20. The combination for use according to any one of claim 1 to 3, nutritional composition for use according to claim 16, the use according to claim 4 or 15, or the method of claim 17, wherein the beneficial metabolites are short chain fatty acids (SCFA).

21. The combination for use, nutritional composition for use, the use, or the method of claim 20, wherein the short chain fatty acids (SCFA) are acetate.

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