Composition for enhancing bone growth and / or bone strength

Abstract

The present invention provides a composition comprising Bifidobacterium longum subsp. iuvenis for use in promoting bone growth, enhancing bone growth and / or bone strength, for example in a young child who has suffered from and / or is suffering from stunted growth and / or faltering growth.

Description

[0001] COMPOSITION FOR ENHANCING BONE GROWTH AND / OR BONE STRENGTH

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to compositions and methods for promoting bone growth, enhancing bone growth and / or bone strength, for example in a young individual who has suffered from and / or is suffering from stunted growth and / or faltering growth.

[0004] BACKGROUND TO THE INVENTION

[0005] 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).

[0006] Bone is a tissue that undergoes constant remodelling as a result of the destruction and de novo synthesis of bone tissue in a complex process involving two main types of cells, the osteoblasts which produce new bone tissue and the osteoclasts which destroy bone, respectively. The osteoblasts, the cells responsible for bone formation, differentiate from precursor cells and express and secrete many enzymes and many structural proteins of the bone matrix, including collagen type I, osteocalcin, osteopontin, alkaline phosphatase collagen type II, fibronectin and annexin. The osteoclasts are multinucleated cells which are responsible for bone loss in a process generally designated bone resorption.

[0007] Moreover, in man and animals, 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. This need is also present in the periodontal diseases, the metastatic diseases of bone, the osteolytic diseases and the conditions under which repair of the connective tissue is required, for example for the cicatrisation or regeneration of defects or traumatisms of cartilage. The stimulation of bone growth is also required in the case of primary and secondary hyperparathyroidism, as well as in osteoporosis associated with diabetes and in osteoporosis associated with glucocorticoids.

[0008] 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.

[0009] 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).

[0010] 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). 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).

[0011] 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 can prospectively have a great influence on future health status. For example the gut flora can have influence on the development of a strong immune system, normal growth and even on the development of obesity later in life. The gut microbiota and its evolution during the development of the infant is, however, a fine balance between the presence and prevalence (amount) of many populations of gut bacteria. Some gut bacteria are classified as "generally positive" while other ones are "generally negative" (or pathogenic) as to their effect on the overall health of the infant. 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 a Bifidobacterium longum subsp. iuvenis to support a healthy microbiome for long-term health. Thus, there is a demand for new nutritional interventions to promoting bone growth, enhancing bone growth and / or bone strength, for example in young individuals suffering from stunted growth and / or faltering growth.

[0012] SUMMARY OF THE INVENTION

[0013] It has now been found that a composition comprising Bifidobacterium longum subsp. iuvenis can promote bone growth, enhance bone growth and / or bone strength in young individuala young individual.

[0014] In particular, it was surprisingly found that a composition comprising Bifidobacterium longum subsp. iuvenis can improve trabecular and cortical bone thickness.

[0015] The present inventors have also surprisingly shown that vitamin K2 production in the gastrointestinal tract is promoted by a composition comprising Bifidobacterium longum subsp. iuvenis and a prebiotic, preferably where the prebiotic is arabinan.

[0016] In one aspect, the present invention provides a composition for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual, wherein the composition comprises Bifidobacterium longum subsp. iuvenis.

[0017] In a further embodiment, the composition for use comprises a Bifidobacterium longum subsp. iuvenis that 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.

[0018] In a further embodiment, the composition for use further comprises at least one further probiotic and / or prebiotic. Preferably where the prebiotic comprises arabinan.

[0019] In an embodiment, the composition for use comprises at least one further probiotic, wherein the at least one further probiotic comprises Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis. In an embodiment, the composition for use comprises Bifidobacterium longum subsp. iuvenis, 2-FL and 3-FL, optionally further comprising Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis.

[0020] In a further embodiment, the composition for use comprises Bifidobacterium longum subsp. iuvenis, 2-FL, 3-FL and Bifidobacterium longum subsp. infantis, optionally further comprising Bifidobacterium animalis subsp. lactis.

[0021] In a further embodiment, the composition for use comprises Bifidobacterium longum subsp. iuvenis, 2-FL, 3-F, Bifidobacterium longum subsp. infantis, and Bifidobacterium animalis subsp. lactis.

[0022] In an embodiment, the composition for use consists of Bifidobacterium longum subsp. iuvenis, 2-FL and 3-FL.

[0023] In a further embodiment, the composition for use consists of Bifidobacterium longum subsp. iuvenis, 2-FL, 3-FL and Bifidobacterium longum subsp. infantis.

[0024] In a further embodiment, the composition for use consists of Bifidobacterium longum subsp. iuvenis, 2-FL, 3-F, Bifidobacterium longum subsp. infantis, and Bifidobacterium animalis subsp. lactis.

[0025] In a further embodiment, the Bifidobacterium longum subsp. infantis is Bifidobacterium longum subsp. infantis LMG 11588 or has an Average Nucleotide Identity (ANI) of at least 99.9% to Bifidobacterium longum subsp. infantis LMG 11588, and the Bifidobacterium animalis subsp. lactis is Bifidobacterium animalis subsp. lactis CNCM 1-3446 or has an Average Nucleotide Identity (ANI) of at least 99.9% ANI to Bifidobacterium animalis subsp. lactis CNCM 1-3446.

[0026] In an embodiment, the composition for use further comprises at least one further probiotic and / or prebiotic, wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL and 3SL.

[0027] In a further embodiment, the composition for use further comprises at least one further probiotic and / or prebiotic wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, and 3-FL.

[0028] In a further embodiment, the composition for use further comprises at least one further probiotic and / or prebiotic wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, and LNnT. In an embodiment, the composition for use further comprises at least one further probiotic and / or prebiotic wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, 3-FL and LNnT.

[0029] In a further embodiment, the composition for use comprises a Bifidobacterium longum subsp. iuvenis that:

[0030] i. is capable of metabolizing one or more of the HMO(s), preferably all of the HMOs; ii. preferentially utilizes 3-FL over 2’-FL; and / or

[0031] iii. 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.

[0032] In a embodiment, the composition for use is provided in the form of a nutritional composition, optionally wherein the composition is provided in the form of a growing-up milk.

[0033] In an embodiment, the present invention provides a composition for use in enhancing bone growth and / or bone strength in a young individual, wherein the young individual suffered from and / or is suffering from stunted growth and / or faltering growth.

[0034] In a further embodiment, the present invention provides the composition for use wherein the composition improves one or more bone parameter selected from: bone mineral density (BMD), trabecular and cortical bone volume fraction (BV / TV) and / or trabecular thickness (Tb. Th).

[0035] In a further embodiment, the composition 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%.

[0036] In a preferred embodiment, the composition 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%.

[0037] In a further embodiment, the composition 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%. In a further embodiment, the composition 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%.

[0038] In a further embodiment, the composition 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%.

[0039] In a further embodiment, the composition 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%.

[0040] In a preferred embodiment, the composition 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%.

[0041] In a preferred embodiment, the composition 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%.

[0042] In a preferred embodiment, the composition 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%.

[0043] In a preferred embodiment, the composition 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%.

[0044] In a further embodiment, the composition for use promotes catch-up growth, preferably wherein catch-up growth is determined using height velocity.

[0045] The young individual may be an infant, young child or a juvenile mammal. The young individual may be a young human child or a toddler. For example, the young individual may be a human less than 1 year old, about 1 years of age or older. In some embodiments, the young individual is a human less than 1 year old. In some embodiments, the young individual is a human from about 1 years to about 3 years of age. Alternatively, the young individual may be a juvenile animal, for example a juvenile pet. The young individual may have suffered from and / or may be suffering from stunted growth and / or faltering growth. The young individual may have been born preterm, with low-birth weight, and / or experienced intra-uterine growth retardation. In some embodiments, the at least one further prebiotic comprises an HMO mixture.

[0046] In some embodiments, the HMO mixture consists of 2’-FL, DFL, LNT, 6SL, and 3SL.

[0047] In some embodiments, the HMO mixture consists of 2’-FL, DFL, LNT, 6SL, 3SL, and 3-FL.

[0048] In some embodiments, the HMO mixture consists of 2’-FL, DFL, LNT, 6SL, 3SL, and LNnT.

[0049] In some embodiments, the HMO mixture consists of 2’-FL, DFL, LNT, 6SL, 3SL, 3-FL, and LNnT.

[0050] In some embodiments, the HMO mixture consists essentially of:

[0051] i. 31 wt% to 82 wt% of 2’-FL, preferably 41wt% to 70 wt%;

[0052] ii. 10 wt% to 27 wt% of LNT, preferably 14 wt% to 23 wt%;

[0053] iii. 4 wt% to 11 wt% of DFL, preferably 6 wt% to 10 wt%; and

[0054] iv. 9 wt% to 34 wt% of 6SL and 3SL combined, preferably 11 wt% to 29 wt%.

[0055] In some embodiments, the HMO mixture consists essentially of:

[0056] i. 16 wt% to 69 wt% of 2’-FL, preferably 22 wt% to 59 wt%;

[0057] ii. 9 wt% to 24 wt% of LNT, preferably 12 wt% to 21 wt%;

[0058] iii. 2 wt% to 10 wt% of DFL, preferably 3 wt% to 8 wt%;

[0059] iv. 8 wt% to 26 wt% of 6SL and 3SL combined, preferably 11 wt% to 22 wt%; and

[0060] v. 8 wt% to 50 wt% of 3-FL, preferably 11 wt% to 43 wt%

[0061] In some embodiments, the HMO mixture consists essentially of:

[0062] i. 34 wt% to 85 wt% of 2’-FL, preferably 40 wt% to 71 wt%;

[0063] ii. 10 wt% to 40 wt% of LNT, preferably 12 wt% to 26 wt%;

[0064] iii. 4 wt% to 14 wt% of DFL, preferably 5 wt% to 10 wt%;

[0065] iv. 9 wt% to 31 wt% of 6SL and 3SL combined, preferably 10 wt% to 28 wt% and;

[0066] v. 6 wt% to 30 wt% of LNnT, preferably 7 wt% to 22 wt%.

[0067] In some embodiments, the HMO mixture consists essentially of:

[0068] i. 20 wt% to 60 wt% of 2’-FL, preferably 22 wt% to 55 wt%;

[0069] ii. 4 wt% to 30 wt% of LNT, preferably 6 wt% to 20 wt%;

[0070] iii. 1 wt% to 12 wt % of DFL, preferably 2 wt% to 8 wt%; iv. 7 wt% to 23 wt% of 6SL and 3SL combined, preferably 8 wt% to 22 wt%;

[0071] v. 10 wt% to 50 wt% of 3-FL, preferably 13 wt% to 46 wt% and

[0072] vi. 3 wt% to 25 wt% of LNnT, preferably 5 wt% to 20 wt%.

[0073] In some embodiments, the composition for use is in the form of a nutritional composition.

[0074] In some embodiments, 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, or a supplement.

[0075] In some embodiments, the Bifidobacterium longum subsp. iuvenis'.

[0076] i. is capable of metabolizing one or more of the HMO(s), preferably all of the HMOs; ii. preferentially utilizes 3-FL over 2’-FL; and / or

[0077] iii. 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.

[0078] 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 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.

[0079] In some embodiments, the 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 composition on a dry weight basis.

[0080] In a further embodiment, the invention provides the composition according to the invention for use in enhancing bone growth and / or bone strength in a young individual, wherein the young individual 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. In a further embodiment, the invention provides a method enhancing bone growth and / or bone strength in a young individual, the method comprising administering the young individual a composition comprising Bifidobacterium longum subsp. iuvenis, optionally further comprising prebiotics and / or probiotics.

[0081] The composition may comprise any suitable Bifidobacterium longum subsp. iuvenis in any suitable amounts.

[0082] The young individual may be at risk and / or in need thereof. In some embodiments, the young individual 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.

[0083] DESCRIPTION OF DRAWINGS

[0084] Figure 1 - Impact of B. iuvenis or B. infantis combined with arabinan on vitamin K2 (MK-7) production in a gut model.

[0085] Figure 2 - Preclinical infection model to test efficacy of Bifidobacterium longum subsp. iuvenis

[0086] Figure 3 - Impact of the 3 nutritional interventions on trabecular BV / TV and trabecular thickness (Tb. Th) assessed through micro-computed tomography on femurs.

[0087] Figure 4 - Impact of the 3 nutritional interventions on cortical BV / TV and cortical bone mineral density (Ct. BMD) assessed through micro-computed tomography on femurs. Figure 5 - Scatter plot of selected proteins against bone readouts

[0088] Figure 6 A & B - Acetate, butyrate, propionate, and total short chain fatty acid concentrations for synbiotic compositions.

[0089] Figure 7 - 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 Bifidobacterium longum subsp. 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 overtime surrounded by a translucent ribbon representing the 95% compatibility interval. Figure 8 - Cross section representation of the femur based on its anterior (A), posterior (P), medial (M) and lateral (L) orientation. Ultrasound probe is stick to the bone based on bone orientation.

[0090] Figure 9 - Region of interest for the measurement of trabecular (metaphysis slice) and cortical (diaphysis slice) microarchitecture.

[0091] Figure 10 - Parameter available from the load deformation curve of a compression test on pigs. Main parameter which will be take into account will be the Failure energy= AUC at force max, elastic energy = AUC at yield point, plastic energy = failure energy - elastic energy, stiffness = slope of the curve during elastic phase.

[0092] Figure 11 - The improvement in femur SOS in piglets receiving Bifidobacterium longum subsp. iuvenis alone at anterior, posterior and lateral orientation of the femur as well as higher femur SOS in piglets receiving Bifidobacterium longum subsp. iuvenis + 3’FL at posterior and lateral orientation compared to control.

[0093] DETAILED DESCRIPTION

[0094] Various preferred features and embodiments of the present invention will now be described by way of non-limiting examples. The skilled person will understand that they can combine all features of the invention disclosed herein without departing from the scope of the invention as disclosed.

[0095] 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. All publications mentioned in the specification are herein incorporated by reference.

[0096] As used in this specification, the words “comprises”, “comprising”, and similar words, are not to be interpreted in an exclusive or exhaustive sense. In other words, they are intended to mean “including, but not limited to“. The terms “comprises”, “comprising”, and similar words also include the term “consisting of“.

[0097] The practice of the present invention will employ, unless otherwise indicated, conventional techniques which are within the capabilities of one of ordinary skill in the art. Such techniques are explained in the literature. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Numeric ranges are inclusive of the numbers defining the range and all percentages disclosed herein are on a w / w basis, unless stated otherwise. As used herein the term “about” means approximately, in the region of, roughly, or around. When the term “about” is used in conjunction with a numerical value or range, it modifies that value or range by extending the boundaries above and below the numerical value(s) set forth. In general, the terms “about” and “approximately” are used herein to modify a numerical value(s) above and below the stated value(s) by 10%.

[0098] As used herein, the following terms have the following meanings:

[0099] The term " young individual" refers to a juvenile mammal, an infant, a young child or a child.

[0100] The term "infant" means a child under the age of 12 months.

[0101] The expression "young child" means a child aged between one and three years, also called toddler.

[0102] 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.

[0103] The term “juvenile mammal” refers to a mammal of comparable age to a human infant, young child or child, such as domestic animals (e.g., dogs, cats) or livestock (e.g., cattle, pigs, sheep, goats)

[0104] A "preterm" or "premature" young individual 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.

[0105] 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 (IIIGR), which refers to a condition in which a foetus is unable to achieve its potential size.

[0106] By the expression “low birth weight”, it should be understood as any body weight under 2500g at birth.

[0107] The expressions “complementary feeding period”, “complementary period”, “transitional period”, “transitional feeding period” and “weaning period” can be interchangeably used and refer to the period during which the milk, either breast milk or formula, is substituted by other foods in the diet of an infant or a young child. The infant or the young child is typically moved or transitioned gradually from exclusive milk-feeding, either breast feeding or formula feeding, to mixed diet comprising milk and / or solid foods. The transitional period depends on the infant or young child but typically falls between about 4 months and about 18 months of age, such as between about 6 and about 18 months of age, but can in some instances extend up to about 24 months or more. For humans, the weaning period typically starts between 4 and 6 months of age and is considered completed once the infant and / or the young child is no longer fed with breast milk or infant formula, typically at about 24 months of age. In some embodiments, the weaning period is between 4 and 24 months.

[0108] The expressions “composition” or “nutritional composition” refer to any kind of composition or formulation that provides a nutritional benefit to an individual and that may be safely consumed by a human or an animal.

[0109] The expression "nutritional composition" means a composition which nourishes the young individual. 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.

[0110] 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).

[0111] 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).

[0112] The expression "infant formula" encompasses both "starter infant formula" and "follow-up formula" or "follow-on formula".

[0113] 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. 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.

[0114] The expression "baby food" means a foodstuff intended for particular nutritional use by infants or young children during the first years of life.

[0115] The expression "infant cereal composition" means a foodstuff intended for particular nutritional use by infants or young children during the first years of life.

[0116] The term "fortifier" refers to liquid or solid nutritional compositions suitable for mixing with breast milk or infant formula.

[0117] 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.

[0118] The "mother's milk" should be understood as the breast milk or the colostrum of the mother.

[0119] The term “oligosaccharide” may refer to a carbohydrate that has greater than 2 but relatively few monosaccharide units (typically 3, 4, 5, 6, and up to 10). Exemplary oligosaccharides include, but are not limited to, fructo-oligosaccharides, galacto-oligosaccharides (raffinose, stachyose, verbascose), maltooligosaccharides, gentio-oligosaccharides, cellooligosaccharides, milk oligosaccharides (e.g., those present in secretions from mammary glands), isomalto-oligosaccharides, lactosucrose, mannooligosaccharides, melibiose-derived oligosaccharides, pectic oligosaccharides, xylo-oligosaccharides.

[0120] The term “polysaccharide” may refer to a carbohydrate that has more than ten monosaccharide units. Exemplary polysaccharides include, but are not limited to, starch, arabinogalactan, laminarin, chrysolaminarin, xylan, arabinoxylan, mannan, fucoidan and galactomannan. It is to be understood that there is not a precise cut-off or distinction between the terms oligosaccharide and polysaccharide, nor is such a distinction necessary to practice the invention.

[0121] The term “glycosaminoglycan” (GAG) or mucopolysaccharide refers to long linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, with the exception of keratan, where in the place of the uronic sugar it has galactose. GAGs are classified into four groups based on core disaccharide structures.

[0122] “Mucins”, as used herein, may refer to a family of high molecular weight, heavily glycosylated proteins (glycoconjugates). Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signaling to forming mechanical and chemical barriers.

[0123] The term “HMO” or “HMOs” refers to human milk oligosaccharide(s). These carbohydrates are highly resistant to enzymatic hydrolysis, indicating they may display essential functions not directly related to their caloric value. It has been especially illustrated 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 the terminal position at the non-reducing ends. Depending on the presence of fucose and sialic acid in the oligosaccharide structure, the HMOs can be divided as non-fucosylated (neutral) or fucosylated (neutral) and sialylated (acidic) and non-sialylated molecules, respectively.

[0124] The expression “fucosylated oligosaccharide” refers to an oligosaccharide having a fucose residue. It has a neutral nature. Some examples are 2’-fucosyllactose (2’-FL), 3-fucosyllactose (3-FL), difucosyllactose (DiFL), lacto-N-fucopentaose (e.g. lacto-N-fucopentaose I, 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 and any combination thereof. Fucosylated oligosaccharides represents the largest fraction of human milk with 2’-FL constituting up to 30% of the total HMOs. Fucosylated oligosaccharides are thought to reduce the risk of infections and inflammations and to boost growth and metabolic activity of specific commensal microbes reducing inflammatory response.

[0125] 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), DSLNT (disialyllacto-N-tetraose), 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. The expressions “at least one fucosylated oligosaccharide” and “at least one N-acetylated oligosaccharide” should be understood as “at least one type of fucosylated oligosaccharide” and “at least one type of N-acetylated oligosaccharide”.

[0126] The term “sialylated oligosaccharide” refers to an oligosaccharide having a charged sialic acid residue. It has an acidic nature. Some examples are 3’-sialyllactose (3-SL), 6’-sialyllactose (6-SL), sialyllacto-N-tetraose (Lst- e.g. Lst-a, Lst-b or Lst-c).

[0127] Suitably, the term “capable of metabolizing the HMO” may mean that the B. longum subsp. iuvenis encodes at least one CAZyme which is capable of utilizing the HMO. For example, the CAZyme may be capable of catalyzing the hydrolysis of a glycosidic bond within the HMO. Suitably, the B. longum subsp. iuvenis may encode at least one, at least two, at least three, at least four or at least five CAZymes that are capable of utilizing the HMO. Suitably, the term “capable of metabolizing the HMO” may mean that the HMO is capable of promoting growth and / or survival of the B. longum subsp. iuvenis (e.g. when added to an anaerobic culture of the B. longum subsp. iuvenis). Growth and / or survival of the B. longum subsp. iuvenis may be determined by measuring the abundance of 16S rDNA - for example using PCR methods.

[0128] The term fibers is used herein to refer to carbohydrates that are indigestible by a human or animal. Such fibers are also discussed in relation to carbohydrates herein. Suitably, the fiber can be fermented by one or more B. longum subsp. iuvenis microorganisms provided in the present use or composition and / or within one or more regions in the gastrointestinal tract within an organism, such as a human or non-human animal. As used herein, the expressions “fiber” or “fibers” or “dietary fiber” or “dietary fibers” within the context of the present invention indicate the indigestible portion, in small intestine, of food derived from plants which comprises two main components: soluble fiber, which dissolves in water and insoluble fiber. Mixtures of fibers are comprised within the scope of the terms above mentioned. Soluble fiber is readily fermented in the colon into gases and physiologically active byproducts and can be prebiotic and viscous. Insoluble fiber does not dissolve in water, is metabolically inert and provides bulking, or it can be prebiotic and metabolically ferment in the large intestine. Chemically, dietary fiber consists of carbohydrate polymers with three or more monomeric units which are not hydrolyzed by endogenous enzymes in the small intestine such as arabinoxylans, cellulose, and many other plant components such as resistant starch, resistant dextrins, inulin, lignin, chitins, pectins, arabinans, arabinogalactans, galactans, xylans, beta-glucans, and oligosaccharides. Non-limiting examples of dietary fibers are: prebiotic fibers such as Fructooligosaccharides (FOS), inulin, galacto-oligosaccharides (GOS), fruit fiber, vegetable fiber, cereal fiber, resistant starch such as high amylose corn starch. As used herein, “added fiber” or “added dietary fiber” indicates an ingredient mainly or totally constituted by fiber which is added to the complementary nutritional composition and whose content in fiber contributes to the total fiber content of the composition. The total fiber content of the complementary nutritional composition is provided by the sum of amount of fiber naturally present in ingredients used in the recipe (for example from whole grain cereal flour) plus amount of added fiber.

[0129] 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).

[0130] The term “probiotic” means microbial cell preparation or components of microbial cells with a beneficial effect on the health or well-being of the host (Salminen S, Ouwehand A. Benno Y. et al. “Probiotics: how should they be defined” Trends Food Sci. Technol. 1999:10 107-10). The microbial cells according to the present invention are generally bacteria.

[0131] The term “cfu” should be understood as colony forming unit.

[0132] The “gut microbiota” is the composition of microorganisms (including bacteria, archaea and fungi) that live in the digestive tract.

[0133] The term “gut microbiome” may encompass both the “gut microbiota” and their “theater of activity”, which may include their structural elements (nucleic acid, proteins, lipids, polysaccharides), metabolites (signaling molecules, toxins, organic and inorganic molecules) and molecules produced by coexisting hosts and structured by the surrounding environmental conditions (Berg, G., et al., 2020. Microbiome, 8(1), pp.1-22).

[0134] The term “SOFA” means short chain fatty acid(s).

[0135] The expression “increasing SOFA production” means that the amount of systemic and / or colonic SOFA, is higher in an individual fed with the nutritional composition according to the present invention in comparison with a standard. The SOFA production may be measured by techniques known by the skilled person such as by Gas-Liquid Chromatography.

[0136] 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.

[0137] 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.

[0138] 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.

[0139] 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.

[0140] Composition

[0141] In a first aspect, the invention provides a composition comprising or consisting of Bifidobacterium longum subsp. iuvenis for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual.

[0142] In a further embodiment, the invention provides a composition comprising of Bifidobacterium longum subsp. iuvenis, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual, wherein the composition further comprises at least one further probiotic and / or prebiotic.

[0143] In a further embodiment, the invention provides a composition comprising or consisting of Bifidobacterium longum subsp. iuvenis and arabinan, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual.

[0144] In a further embodiment, the invention provides a composition comprising or consisting of Bifidobacterium longum subsp. iuvenis and Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual, preferably wherein:

[0145] (i) the Bifidobacterium longum subsp. infantis is Bifidobacterium longum subsp. infantis LMG 11588 or has an Average Nucleotide Identity (ANI) of at least 99.9% to Bifidobacterium longum subsp. infantis LMG 11588; and

[0146] (ii) the Bifidobacterium animalis subsp. lactis is Bifidobacterium animalis subsp. lactis CNCM 1-3446 or has an Average Nucleotide Identity (ANI) of at least 99.9% ANI to Bifidobacterium animalis subsp. lactis CNCM 1-3446.

[0147] In a further embodiment, the invention provides a composition comprising or consisting of Bifidobacterium longum subsp. iuvenis and an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL and 3SL, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual.

[0148] In a further embodiment, the invention provides a composition comprising or consisting of Bifidobacterium longum subsp. iuvenis and an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, and 3-FL, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual.

[0149] In a further embodiment, the invention provides a composition comprising or consisting of Bifidobacterium longum subsp. iuvenis and an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, and LNnT, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual.

[0150] In a further embodiment, the invention provides a composition comprising or consisting of Bifidobacterium longum subsp. iuvenis and an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, 3-FL and LNnT, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual.

[0151] In a preferred embodiment, the invention provides a composition comprising of Bifidobacterium longum subsp. iuvenis, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual, wherein the composition also comprises Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis, and an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL and 3SL.

[0152] In a further preferred embodiment, the invention provides a composition comprising of Bifidobacterium longum subsp. iuvenis, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual, wherein the composition also comprises Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis, and an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, and 3-FL.

[0153] In a further preferred embodiment, the invention provides a composition comprising of Bifidobacterium longum subsp. iuvenis, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual, wherein the composition also comprises Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis, and an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, and LNnT.

[0154] In a further preferred embodiment, the invention provides a composition comprising of Bifidobacterium longum subsp. iuvenis, for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual, wherein the composition also comprises Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis, and an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, 3-FL and LNnT.

[0155] Vitamin K2

[0156] Vitamin K2 (menaquinone) may have the general formula below:

[0157]

[0158] Vitamin K2 consists of various forms, differing in the number (n) of isoprenyl units, wherein n may range from 4 to 13. The various forms are indicated by a suffix (-n), for example, menaquinone-4 (abbreviated MK-4) has four isoprene residues (n=4). MK-4 may be formed via metabolic conversion of phylloquinone during its absorption in the intestinal mucosa and in other organs. Other menaquinones may be produced in the gastrointestinal tract by specific anaerobic bacteria of the colon microbiota.

[0159] The present inventors have surprisingly found that vitamin K2 production in the gastrointestinal tract is promoted by a Bifidobacterium longum subsp. iuvenis.

[0160] In one embodiment, the present invention provides use of a Bifidobacterium longum subsp. iuvenis to promote vitamin K2 production in the gut of a young individual.

[0161] Bifidobacterium longum subsp. iuvenis

[0162] Bifidobacterium longum subsp iuvenis (B. iuvenis) 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 (B. 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 I-5684, CNCM I-5685, CNCM I-5686 and CNCM I-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 etal. 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 etal.', 2022, Cell 185, 1-18; published online 1 November 2022; https: / / doi.orq / 10.1016 / i.cell.2O22.10.011).

[0163] 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.

[0164] 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.

[0165] 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.

[0166] 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.

[0167] 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.

[0168] 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.

[0169] 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. 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.

[0170] 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.

[0171] 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.

[0172] 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.

[0173] 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.

[0174] 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.

[0175] 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. 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 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.

[0176] 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 metogenomics 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).

[0177] 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)).

[0178] 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): 2380-23811 (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.

[0179] 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.

[0180] 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.

[0181] 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: / / qenome.iqi.doe.qov / portal / ). Analysis project numbers and taxon numbers for each genome are as follows:

[0182] Strain JGI analysis project JGI taxon

[0183] B. longum NCC 5000 Ga0527908 2951181949

[0184]

[0185] B. longum NCC 5001 Ga0529016 2951184202

[0186] B. longum NCC 5002 Ga0529017 2951186501

[0187] B. longum NCC 5003 Ga0529018 2951188792

[0188] B. longum NCC 5004 Ga0529019 2951191018

[0189]

[0190] In some embodiments, the B. longum subsp. iuvenis for use in the present invention is isolated from a human.

[0191] In some other embodiments, the B. longum subsp. iuvenis is not of the subspecies B. longum subsp. longum or B. longum subsp. infantis.

[0192] Suitably, the B. longum subsp. iuvenis is provided as a probiotic. Suitably, the B. longum subsp. iuvenis is provided in a composition.

[0193] 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 young individual 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 young individual in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less.

[0194] In one embodiment, the B. longum subsp. iuvenis is viable.

[0195] Antibiotic resistance

[0196] 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).

[0197] 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.

[0198] 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.

[0199] 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.

[0200] 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.

[0201] 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.

[0202] 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.

[0203] Suitably, the B. longum subsp. iuvenis strain is not resistant to any one of tetracycline and erythromycin.

[0204] Suitably, the B. longum subsp. iuvenis strain is not resistant to any one of tetracycline, erythromycin, clindamycin and ampicillin. Suitably, the B. longum subsp. iuvenis strain is not resistant to any of tetracycline, erythromycin, clindamycin, ampicillin, gentamycin, streptomycin, chloramphenicol and vancomycin.

[0205] 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 tef(VV 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.

[0206] SEQ ID NO: 1 MKIINIGILAHVDAGKTTLTESLLYASGAISEPGSVEKGTTRTDTMLLERQRGITIQAAVTSFQWHRCKVNIVDT PGHMDFLAEVYRSLAVLDGAILVI SAKDGVQAQTRILFHALRKMNIPTVIFINKIDQAGVDLQSWQSVRDKLSA DIIIKQTVSLSPEIVLEENTDIEAWDAVIENNDKLLEKYIAGEPISREKLVREEQRRVQDASLFPVYYGSAKKGL GIQPLMDAVTGLFQPIGEQGSAALCGSVFKVEYTDCGQRRVYLRLYSGTLRLRDTVALAGREKLKITEMRIPSKG EIVRTDTAYPGEIVILPSDSVRLNDVLGDPTRLPRKRWREDPLPMLRTSIAPKTAAQRERLLDALTQLADTDPLL RCEVDSITHEIILSFLGRVQLEWSALLSEKYKLETWKEPTVIYMERPLKAASHTIHIEVPPNPFWASIGLSVT PLPLGSGVQYKSRVSLGYLNQSFQNAVRDGIRYGLEQGLFGWNVTDCKICFEYGLYYSPVSTPADFRSLAPIVLE QALKESGTQLLEPYLSFTLYAPREYLSRAYHDAPKYCATIETVQVKKDEWFTGEIPARCIQAYRTDLAFYTNGQ SVCLTELKGYQAAVGKPVIQPRRPNSRLDKVRHMFSKIT

[0207] 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.

[0208] SEQ ID NO: 2 MRFDNASNWYYCLIQMNIINLGILAHIDAGKTSVTENLLFASGATEKCGRVDNGDTITDSMDIEKRRGITVRAS TTSIIWNGVKCNIIDTPGHMDFIAEVERTFKMLDGAVLILSAKEGIQAQTKLLFNTLQKLQIPTIIFINKIDRAG VNLERLYLDIKTNLSQDVLCMQTWDGSVYPVCSQTYIKEEYKEFVCDHDDNILERYLADSEIPPTDYWNTIIAL VAKAKVYPVLHGSAMFNIGINELMDAITSFILPPASVSDRLSAYLYKIEHDPKGHKRSFLKIIDGSLRLRDWRI NDSEKSIKIKNLKTIYQGREINVDEVGANDIAIVEDMEDFRIGDYLGAEPCLIQGLSHQHPALKSSVRPDKPEER SKVI SALNTLWIEDPSLSFSINSYSDELEISLYGLTQKEIIQTLLEERFSVKVHFDEIKTIYKERPIKKVNKIIQ IEVPPNPYWATIGLTLEPLPLGAGLQIESDISYGYLNHSFQNAVFEGIRMSCQSGLHGWEVTDLKVTFTQAEYYS PVSTPADFRQLTPYVFRLALQQSGVDILEPMLYFELQIPQEASSKAITDLQKMMSEIEDISCNNEWCHIKGKVPL NTSKDYASEVSSYTKGLGIFMVKPCGYQITKDGYSDNIRMNEKDKLLFMFQKSMSLK

[0209] 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. SEQ ID NO: 3 MRNIKDTQNFLHSKELVRHLIGICNIKLDDWIEIGPGKGIITNELAHKARKWAIEFDEELYEKLKNKFQSNNK VDIIYGDILNYTPRIPSYCVFSNIPFNITSEILNKFLSDKKNEKMFLIMQYEPFIKYAGNPYGAETLRSMLYKPF FDMDLKYRFDPSDFKPAPQARIVLASFERKQFPDVKKEEEKLYKDFLAYIYTNKGETFFAKIKTLFSSNQIKRVW GQIKIDKTTKISEVPYESILKVFKLFFLYGTDANKQLWNSFNNMNKQNNKLQKNHRNNSKAKSWNSNRKRKPYH RNNV

[0210] 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.

[0211] SEQ ID NO: 4 MSAYGHGRHENGQNFLTNHKIINSIIDLVKQTSGPIIEIGPGSGALTHPMAHLGRAITAVEVDAKLAAKLTQETS SAAVEWHDDFLNFRLPATPCVIVGNIPFHLTTAILRKLLHAPAWTDAVLLMQWEVARRRAGVGASTMMTAQWSP WFTFHLGSRVPRTAFRPQPNVDGGILVIRRVGDPKIPIEQRKAFQAMVHTVFTARGRGIGEILRRAGLFSSRSET QSWLRSRGIDPATLPPRLHTNDWIDLFQVTGSSLPHHRPISPSGSSQRPPQQKNRSRRR

[0212] 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.

[0213] SEQ ID NO: 5 TTGCCTACTATTGAACAGCTCGTCCGTAAGGGACGTCAGGCAAAGCCGAAGAAGTCCAAGACTTTGGCCCTGAAG GGCAGCCCGCTGCGTCGCGGCGTGTGCACCCGTGTCTACACCACCACCCCGAAGAAGCCGAACTCGGCTCTGCGT AAGGTCGCTCGTGTGCGCCTGTCCTCGGGCATCGAAGTCACCGCCTACATTCCGGGCGAGGGCCACAACCTGCAG GAGCACTCCATCGTGCTCGTGCGCGGCGGCCGTGTGAAGGATCTCCCGGGTGTGCGTTACCACATCGTGCGTGGC GCGCTCGATACCCAGGGTGTCAAGGACCGTAAGCAGGGTCGTTCCCTGTATGGAGCAAAGAAGGCGAAGTAA

[0214] 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. SEQ ID NO: 6 MPFALYMLALAVFVMGTSEFMLAGLLPAIATELDVSVGTAGLLTSAFAVGMWGAPVMAAFARRWPPRLTLIVCL LVFAGSHVIGAMTPVFSLLLITRVLSALANAGFLAVALSTATTLVPANQKGRALSILLSGTTIATWGVPAGALL STALGWRTTFWAIAILCIPAAVGVIRGVTNNVGRSETSATSPRLRVELSQLATPRLILAMALGALNNGGTFAAFT FLAPIVTETAGLAEAWVSVALVMFGIGSFLGVTIAGRLSDQRPGLVLAVGGPLLLTGWIVLAWASHPVALIVLV LVQGFLSFGVGSTLITRVLYAASGAPTMGGSYATAALNIGAAAGPVLGALGLATGLGLLAPVWVASVLTAIALVI MLLT RRALT KTAAEAN

[0215] Carbohydrate-Active Enzymes (CAZymes)

[0216] Suitably, the B. longum subsp. iuvenis encodes a specific profile of Carbohydrate-Active Enzymes (CAZymes).

[0217] 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).

[0218] CAZymes include glycoside hydrolyases (GH), glycosyltransferases (GT), polysaccharide lyases (PL), carbohydrate esterases (CE), and carbohydrate-binding module families (CBM).

[0219] 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.

[0220] 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.).

[0221] 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.

[0222] SEQ ID NO: 7 ATGAAACGAACTGACATCCACCTGCGCGATCCGTTCGTCCTGCCTCACGACGGTGTCTATTACCTGTATGGCACC CGCGCTGATAACGTGTGGGGCGCGATGGATGGTTTTGATTGCTACACCAGCCGCGACCTTGACAATTGGGAGGGT CCGTTCGAGGTGTTCCACAAGCCGGATGAATTCACGGCCGACCGTGCTTACTGGGCGCCCGAATGCTACGAGCGA GACGGTGTATTCCACCTGATTGCCACGCTCGGCGAGCCGGACGGGCGCAAAAGCGTGCACATGCTACGCGCTGAT AGTCCGCTTGATCCGTTCGAATATGTCTGCCGGCTGACCGATCCGAATCAGTCCTGCATTGACGGAACTCTGCAT GGTGAAGGTACCGATATGTGGCTTGTCTACTCGCATTCCTTGGAGGATGTGCCCGCCGGAGACATGGATGCCGTA CGTCTGTCCTCCGACCTGACTCGGACGGTGGGGGAGAGCATGACATTGTTCCAGGCCTCGGATGCGCCGTGGGCG GTGCCGGTGCCGTTCGCGAAAGCGGAATTCGGCATCGACGAGGACGCCTACTTCTCCGATGGTCCCTGCCTGTGC AGGCTTTCCAACGGACGGCTGGCGATGCTGTGGTCGAGCTGGTCGACGGAAGGCGGATATGCAGTCGGCCAGGCC ATCAGCGAATCAGGGTCGATTGCTGGGCCTTGGACGCAATGCCCCGAGCCTCTGCTTAGCCACGGCGGCCACGGC ATGCTGTTCAACGGTCTCGATGGCGTGCTGCGTTACGCGGTCCACTCGCCCAACGACCCCGGCCAGGAACGGCCT ACGTTTTTGTGCGTCGAAGAACAAGACGGGCTGCTGACGATTACGGAATAG

[0223] 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.

[0224] SEQ ID NO: 8 MKRTDIHLRDPFVLPHDGVYYLYGTRADNVWGAMDGFDCYTSRDLDNWEGPFEVFHKPDEFTADRAYWAPECYER DGVFHLIATLGEPDGRKSVHMLRADSPLDPFEYVCRLTDPNQSCIDGTLHGEGTDMWLVYSHSLEDVPAGDMDAV RLSSDLTRTVGESMTLFQASDAPWAVPVPFAKAEFGIDEDAYFSDGPCLCRLSNGRLAMLWSSWSTEGGYAVGQA ISESGSIAGPWTQCPEPLLSHGGHGMLFNGLDGVLRYAVHSPNDPGQERPTFLCVEEQDGLLTITE

[0225] 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.

[0226] 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

[0227] 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

[0228] 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.

[0229] 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 ATAGI SLTLWRKRRA SEQ ID NO: 12 MGKLIRKATGLTVGVATLLAGLVLPMTASAESASPIDASPIIHYSFDNALTSKTIANEGSAANSDATLSGDATVA NGQINLTGSQTISVPTTAIAGKKDVTVSIWLKNNYGNGNTAAAYIGAAKTGNYPANGYWLLNPANPSGYAKSVMT NATAADPNNSPWGTEVGPGSTNAAITGTKATSDLALYTTVINGTNSTMSFYLNGKQVGDATYAI PAGGLTNYGDL VAYIGKSSYADPNSKLDVDDYAVYDTAI SAADVTKLYDVQVLDKAEAAVKAAVPASATEDFTLPTSAAGVSVAWK SDNAAIAVDNATGKATVTRPAATAADAEVTLTVTFGNNAKTAAYTVLVPKQLSDAEQAKADLDAITIEDSDDIRS NFSVPTKGNNGSTISWGVTGGKDIATLGEGVSDKSRTVTVKRPAAGSDAATVTLKATAKYDTATETKTFTVTIQP MPAAEEKDEAYVWAFFTGEGVGGEKISLAASKGNDALDWNTLNNGTPIFTSEFGEKGLRDPFIMKSKDGDKFYML ATDLKIDGRAPLNGLNGFAGAQANGSKYIEIWKSDDLVNWSKQSHVKVSSDYAGNTWAPEAYYDEEIGKYWYWA SNLYDNTDENSRKQLTYNRMVYVTTDDFVNFSDPTVWIDVDRRGGAGSGSIDVTVQKVGDTYYRIYKDENTMSLR QEKSTDLTAAIGGAGVKNYADALKGSAWSEVATNIGKGQANGYGKTFTSGEGPSLFKANDGDVNGYQYYLFADQP SYHQGPNHYVPMATEDIASGQWTVIGNKMPEANFPTNSDGGKPRHGTVLPVTRAQYQKVLEAYAPAVAVKSVDAL SAETTVGVAPTLPETAHLTHADGSVSDVAVEWDAIDASFYAKTGTFTVKGITQDDSRMPVEATVIVNGIDLSKAT VTVEPNEFTADGAAKEPAVTWLDGATLKEGADYTVAYTNNVEPGTATVTVTGAGKYSGTVSATFTIKAAEPGST LDKSKLQALVDKVKGYNKADYQSGWDAFAVALADAQQVLQNSTDQQEVDKALSRLQSAVDKLVKKSGDSGKTDGK DDGTQKPAAKPGSALSNTGASVFGVGITAVILLAAAGAAYAFRKRRA

[0230] 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.

[0231] 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

[0232] 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 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.

[0233] SEQ ID NO: 14 MTTKPSIGKRLLGAMLAVPMALAGMGIGATTAVAADTVPTNNLIAAYDFTTKPSDGKTVANSAPNATLGAAEVQN SADSLWADDALTLSGGAKTGTGDWVKLPSNLLSGKDAATVQLEVKADSSMLNAFHFLWNIGNDSSDTEYFFATLN CGSSRNPLVGLKSGGTETLVQSSSCVAKADQWLSVTATIDGTAAKLYIDGTQVASGTVPAKLSSVKDQSLNTIGR SPWPDNLFKGAVSNFRVYDAALTADQVAAISTADASIHAGELTGSVLNGIIIPTTVDDPFISLPTANGVTWASSD SSVIATDGTVNQPAKGEAAKTVTLTAAVTIRGQTATKEFTVTVNPTTKTAAEQLKEAAAGYVIPSWRSGDALPA AVNGTTVTVTSTKDVAVEDGKITIDGDEATTGTITVEFSKNGLAGIEPITKVFTVKVLPAAKSATIAAYDCNATS ADEANNGDIAYSMHLALQNADGSYTPYNENYGIFFARSPKAQNLNENLDGNDYRSLKDPSLLRMADGTYGVISVR TNRGTATGDSTAKSSVLIATSEDLLTYSEQENSGSIVDLGETNGVNAPYAVYDTASKQYWGWADDNGVAKYTTF DSLKGSASKHGSVLYGSIAKSGVLDADGVQGIANFRSGATIAVDEATVKALNTRYGRSENTGTSNLTDITVEKGS SIDEMTSQLPKNVDLTYSDGSTGSLPISSWNTEGIDLTKVGDYTVTGTVKQTEYQIPFAEDRADPSVYKWQWTHE VDGKEVTETKFLMIASNDIQGDVTWQHGSPHMPFRMADTISGLADEPGNPNALIQSNGYNNKEVSLLKAGDKDSE GNAIMHSFWAPEIHEIDGRLTILFMAGYGNTWSNGKSVYMQLKQDADGHDLDPTDPDNWTVPTPIYRNDASLLNG NKQLAATASGGVGMSLDMTYFQDADGRSYYAWQQLGATYIATMDPKDPAHVTSSPVRIVTPEYAWNAAIAEGPNV TLRDGKLYLMFSGSGVGKTYTTGLAVADASGTDLTDPASWTVLNYPIQKSGPFNGEMQLGTGHGMWSEDEDGNQI YVFHAYATKNLGSVNAAGRDMFVRRVHWAADGMPVFDMSSSEELANKIVSVTVHWDDAVAVDKSGLSKALASAK QLHGSDYTAASWKAFATMLASAEKVYADDTATQKDVDDTTVALVKAQAALVKIDGSDSGDGSGDSTKPSDGSSVD AGDKTCNNLGLSKTGAAVLSLSGVAVALAVAGIALTLQRKRRA

[0234] 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.

[0235] 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

[0236] 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.

[0237] 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

[0238] 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.

[0239] 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

[0240] 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.

[0241] 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

[0242] 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.

[0243] Suitably, the B. longum subsp. iuvenis strain comprises a GH43_17, GH43_22, GH43_27, GH43_29 and GH121 gene as defined herein.

[0244] 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.

[0245] Suitably, the present B. longum subsp. iuvenis strain comprises a glycosyl hydrolase family gene that encodes a CAZyme that targets arabinogalactans.

[0246] 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.

[0247] 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 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.

[0248] SEQ ID NO: 20 MKINNKGKGALIAAITAAATLLSCGLAAASASAAGVNYLPTIGQVPTYTKFQPTADPGKNASDYFQPYWYAKNAN DNGGTHIQAHGGQWKVGDAYYWYGEDRSNGYDNSPGVHAYMSTDLYNWTDLGVALRAVTSKSQLTDKSNADYAY FDKAYNLTKSDGSVDAAKADAIFPYLNTNPDQDGDGAVDSVQGIFERPKIIYNKKNKQYVLWWHSDGSTTPGGSN YARALAGVAVSDNPAGPFTMVGAYRLPNQNNWKEAAGNPSWGENGDSRDMTVFVDPKDDSAYVLYSSEANATLYI AKLNDDYTNWKTTNVDQSEGQKQYSADGQYPYILADATTDAPVRGEDFQIVKQNGSLEAPAVFQYDGRYNIIAS GATGWAPNKQTYYTADSMLGSWTRGVEKDDINENTWYNNMPEGADGLLSVGDTRGTTFGSQSASVLAVDQEKGHF IYLGDRWDSGKADSTYVWLPLTIGENGTIEMHNPAQEGEPDGWDLSYWGNHGSAKGKLVNWTVETGDDLPKTVNT GGTVTLPDTVNVKEGDDTIATKVTWNVEGGTAVSKSTKAAGNTYAFNVPGTYTITGTLAESSNFNPGRTFRRTID VSCSNPISGSWKEAHWKGGSACQVSASGGAYDFTITDNANRGVWTDRNEGSAVYQPDALDVNEMLETTVKPLDLG GNGDPRAGLWRNGLTGANGGKGYATLLASPSGVYMQYDSNADGYIDKETSHVGTGFGDQVQLKLERTSTDTLKG YWRASANDEWQDVATVTLTGADVTGLDAGAFATSNSNAGAFTVAFNGTAFGSQTAAVESIAAKGPEATIAKRQTL AHKDVTVTATLTNGKTRVLEPDEYTLEGFDTTKLGEQTVTVRLVTDSSVTATLTVTVESNLARLFCSSAAASKYE PASSWASASTADLTCDNNLSTNWSNWGTGDTSPWLSYTFDKAYQLGKLSVAVDKAKGEAAPKSFTVSYLAEDNAT WTDATLPAVTVNGAAGAVTEADVSALPATKGIRLNFTYADGNDYAKIAEVRIAEGEATPKPQPSSNANLADLTVD GKTVDGFSADITEYAGALAGDAASYPTVEATAADAKATVQVEQASTENSGVATVTVTAEDGTAETYTVTFGELPQ LAELAVEVTKDSYQVGDKFNAADVKVSAIYKVGDTETLRKLIDPTDGDLKFTGFDSATAGTKTITVSYRGVNATF EVTVTATEVTPGPGEQKPGDTNNPGNTAKPGNTATNKPAANGAAPLSNTGVAVAAIAVWWLTAAAGALLVIRK RRA

[0249] 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.

[0250] 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 GAGAT GC GT GT CT T C CAGC GT C GAT AA

[0251] 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.

[0252] SEQ ID NO: 22 MNVTITSPFWKRRRDQIVESVIPYQWGVMNDEIDTTVPDDPAGNQLADSKSHAVANLKVAAGELDDEFHGMVFQD SDVYKWLEEAAYALAYHPDPELKALCDRTVDLIARAQQPDGYLDTPYQIKSGVWADRPRFSLIQQSHEMYVMGHY IEAAVAYHQVTGNEQALEVAKKMADCLDANFGPEEGKIHGADGHPEIELALAKLYEETGEKRYLTLSQYLIDVRG QDPQFYTKQLKALNGDNIFPDLGFYKPTYFQAAEPVRDQQTADGHAVRVGYLCTGVAHVGRLLGDRGLIDTAKRF WTNIVARRMYVTGAIGSTHVGESFTYDYDLPNDTMYGETCASVAMSMFAQQMLDLEPKGEYADVLEKELFNGSIA GISLDGKQYYYVNALETTPDGLDNPDRHHVLSHRVDWFGCACCPANIARLIASVDRYIYTERDGGKTVLSHQFIA NTAEFASGLTVEQRSNFPWDGHVEYTVSLPASATDSSVRFGLRIPGWSRGSYTLTVNGKPAVGSLEDGFVYLWN AGDTLEIALELDMSVKFVRANSRVRSDAGQVAVMRGPLVYCAEQVDNPGDLWNYRLADGVTGADAAVAFQADLLG GVDTVDLPAVREHADEDDAPLYVDADEPRAGEPATLRLVPYYSWANREIGEMRVFQRR

[0253] 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.

[0254] 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

[0255] 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.

[0256] 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

[0257] 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.

[0258] 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

[0259] 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. SEQ ID NO: 26 MTATISNGVSASYSPAEDELGAADPTALLAESGDLKPLAERTYTNPVPYADGKSHTAPDPFVLKYRDLYYCYATD EHGILVSTSPDMVHWTSHGFCYTEAGRRNFWAPSVILINGVFHMYFSNMPAEETDTHTEIMRVAVSEDPLGPFEK KAELFNTFAIDSQWYGDDGQLYLLYADNQVTGLSDDRPGTSVMIDRLVTPYSRENKPRPLIVPTMDEEIFARNR FGDGRDWHTVEGATYFAYRDRAFITYSANAYEHEDYFVGYSYAQLPNKQADAHIDQLDWTKQLNENRFDPLLIRS PKVEGTGHNSIVKAPNAVDDWIVYHGRNADDELYVGTEQRVMRIDPLYYAEGGLDTPGPTAAAQSAPLYGTVHDD FADGLNAGWSVISGAAHTESDVDGHALVADESSVFIAVSGKSSATQVIDVWAKAPVTPLGARFGIWRYQDANNL TKLEVDAGRQVISWDVIGGVASERVTNADLHDFDSHAWHEYRLERRYCRLEIRIDGRFAASCTISDKPGRAGLF SLRTGAAFSAYAATEHVNLWGAGLRDLGRELHADRRLVIDGGVRSSGVCPVTLELAYPLVSNRFVLDFAGQTSRG QALLSLGEYRLSGTASSVEFMRNGKSLPSTPEPARLRVFEDNVRRDRSGRAVLTIRIEALNGTMRLHLRGKTWQV PFADNAARARITLDRASLTGYERTSLESSIEERSASGN

[0260] 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.

[0261] 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.

[0262] Suitably, the B. longum subsp. iuvenis strain comprises a GH43_17, GH43_24, GH127, GH30_5, and GH 43_32 gene as defined herein.

[0263] 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.

[0264] 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.

[0265] GH43_ 17 gene cluster

[0266] 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.

[0267] 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.

[0268] 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

[0269] 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.

[0270] SEQ ID NO: 28 MTTSFTIDGNALIWTGDGETLRIEPWEENSVRVRATRNRGFGPVDWALLEPKNESGRVADIAVGEDGEHASLTNG SITVKADSNHAPLLSAGYETFRCDLSFWNAEGELLFREYPQGGSLLLKARDYTPVSGESFAVTTSFSADPKERLY GMGEYQQDVLDLKGSTFELAHRNSQASVPFWSSKGYGFLWHNPAIGRATFGRNRTEWAAQSTDQIDYWVTAGDS YAQIESQYADATGHAPVMPEWGMGFWQCKLRYWNQEQLLDVARGFKSRNIPLDLIVIDFFHWPHLGDYKFEDEFW PDPEAMVAELNSMGVKLMVSVWPQVSVSSENFVEMKRNNYLVSAEAGLNLDMMFEEPCVNYDPTNPGARKFVWDK CKANYWDKGVRAFWLDEAEPEYGVYDFRNYRYHMGSDLNVGNVYPQAYNRGFYEGQIEAGMEGEIVNLTRCAWAG SQRYGSLVWSGDVGSTFADLKSQITCAIHMGMAGIPWFTTDMGGFHDGVIDSDSFKELLARWCAFSCFLPVMRNH GDRSLGESTGKQTITKATGEHRSPSGADNEPWSYGPEMESIFRKYIAVREVMRPYTRELFQSAHEQGQPLVRGLF YEFPTDEHVADIADEYLYGPDILVAPWEAGAASRSVYLPGDETTTWTDLRDGAVYAGGQSIESSAAIDTVPAFA RDGRDHGLIGLL

[0271] 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.

[0272] 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

[0273] 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. SEQ ID NO: 32 MTHRSTWWKTALGIILTLIMMFPVYWMINISFTGKASIRSGDLWPKDFTFDNYARVIADQMPYLGTSILVAVCCV ILTLVIALPAAYALALLRCPGSGALSFLLIVAQMIPAWMSLGFYEIYNNIGLLDTLPGLILADSTIAVPFAVML LTSFMAGIPRSLLEAAEVDGASRTRRFFSIVIPLSRNSIVTVSLFAFLWSWSDFLFASTLDSGGGKMRPITMGLY NYI GAQTQEWGPMMATAVLAS I PAT I LLVFAQKYVAAGVTAGAVKD SEQ ID NO: 33

[0274] MTASTTSPVRRAKSGTPVRAKLAIAGFIAPLIIYLVI FYAFPLIQNVSMSLHRYTRRTFVTGDALFVGLDI YKEV ISSVEFWPWGQTFVFVWSLIFQYVIGLALAVFFNDNFKLSGVLRGIMLVPWLLPLIVSGTVWQWMMDPDSGIL NMFLGLFDIEPIWWLQADNSLWAVIIANIWLGIPFNLVILYSGLQNISGDLYEAASLDGCNAWQRFWKITFPLLK PVTSITLLLGFVYTLKWDVIWMMSQGTGTSRTLATWAYSMAFGKGTSMTIKYSEASVLGTILIIVALIFGLIYL RVQKTQETC SEQ ID NO: 34 MKSNTALKITAALCSCAMLVGVSACGSSNSTTDDKVIEWWDDWTRHEDGSEFDKLVKACAPEGYTIERQAIATSD LLNNLTTAIKEDNGPDVAVIDNPMIPSAVDAGLVAGSDETGLDVSAWDENLEAPGWDGQAYGVPLGGSNTLGLM YNPTIIEAAGVDVSTITDWDSLNAAIKKWDAGYKGITFSGISGEEGVFQFLPWFWGAGGDLSKLDSQAQKDAED LLSGWISKGWAPKSATTNTQSASWDLFLAGDYGFAEIGTWMQSEADEAGAKLIPIPAKDGGVATVPTGGEFAMVA YHKKDAESHYKLANQVIECLSEDETLLKVSNALSNLAAKKAVRAEQLAASDGLAQWKESIENAAGRTSDLGLKYE EASASISESL LAALNAA

[0275] 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.

[0276] SEQ ID NO: 35 ATGGTGACCATCAACGACGTGGCGCGGGAGGCAGGAGTCTCCAAAACCACGGTCTCATTCGTGCTTTCGGGCTCG CGCCCCGTTGCTGCAGCCACCGAACAACGTATCCGTGAGGCAATGGACAGACTCGGCTATACCGTCAATCATGCC GCCCGCAGCTTGTCCACTTCGAAGACCATGACCATAGCCGTGGTGACCAGCAACCGGCAGGACGCCTACTTTGAC ATTGCCCGTGGCACATACATCAACGGCTTATCCCGAGCAGCCGCCGAAACCGGCTACGACATGCTCATCACTAAC GATCCAGACGGCTCCGCTACGGAGAACGCCTGCCAATCACACAAGGCGGATGGGCTGGTTTTTTTAGACGTCAGG CAGAACGATCCGCGTGTGCCGATTGCCGCTGAATCCGGCATTCCAACAGTCTCGCTAGGAGTCCCAGTCAATCCA ATGAATCTTGATGTGGTCGACACCGACTTCACGGACATGGCGGCCTCGACCATGCGTACACTGCACGATGCCGGA CACCGCCGCGTCAGCGTCATCACGCTCAGTAGCCGGGTGATTGCCGAACAACTCAACGACACCGCTCGATTCCTC AGGGAAATCGAACGTTCCGGAGAACGACTTGGCATGCATGCCACTATCCGACATTGCTCTACAAGGCCCGGAATC ATCGACACAGACATCGCTCGCATTCTTGACGGTCGAGGTGAGGACACCGCATTCGTCATCCATAATGAATCGGCC GTATTGGTGTTCAGACGGGCAGTGGAACATCGCGGACTGCGCATCCCCGAGGATATCTCCGTCATCGCCATCAAT GAAAAGCAGATGTCGGACGCTCTGTATCTGCCATATTCCGCCTACGAAAACGACGTGGAACTGGTCACCCAATCT GCCGTCAATACGCTTGTGGACCGTATCGAACATCCCGAGCTGACGCCGACACGAACGTTGATCAAGGCCTCGTAC ATAGATCGAGACTCCGTGGCCAATATCTGA

[0277] 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.

[0278] SEQ ID NO: 36 MVTINDVAREAGVSKTTVSFVLSGSRPVAAATEQRIREAMDRLGYTVNHAARSLSTSKTMTIAVVTSN RQDAYFDIARGTYINGLSRAAAETGYDMLITNDPDGSATENACQSHKADGLVFLDVRQNDPRVPIAAE SGIPTVSLGVPVNPMNLDVVDTDFTDMAASTMRTLHDAGHRRVSVITLSSRVIAEQLNDTARFLREIE RSGERLGMHATIRHCSTRPGIIDTDIARILDGRGEDTAFVIHNESAVLVFRRAVEHRGLRIPEDISVI AINEKQMSDALYLPYSAYENDVELVTQSAVNTLVDRIEHPELTPTRTLIKASYIDRDSVANI

[0279] 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.

[0280] SEQ ID NO: 37 ATCGCCGAGTTCCATTACGCTATCGGGCATTTTCATTGTGCCGGTCATCGGATTGGTTGCTCAGGCATTCCCGGA CAGCTCGCTCTCCAGCGTGCAGATGATTGTTTCGGCATCACTCTGACCGCACTGGTTGGCGCTTGGCTGACCGGC AAACTCGCCAGCATTCTATCCCGGAAGACCGTGGCACTGATTGGTGCAGGCGGCATGCTGCTGTTCGGTCTGCTG CCGTACTTCGTGCATTCCAGTCTGGCTGCAGTCATCGCGTTTTCCGCGTTGATGGGCGTATGCCTAGGCTTTATC AACAACGTGCTGCCTACTTTGATCTCCGTGCACTACGAGGGCGATGAGCGACAGTCGATTATGGGTCAGCAGGTT GCCGTGGCCAGCATCGGTGCGATGGTGTTCATGACCGTGGCCGGCAAACTCGCCACCGCACAGTGGTATCACGCC TACCTCATCTACTTGTTCGCCGCCGTGGTGCTGGTGGTCTGCGCATTCACGCTGCCCACCAAGAATGGTGAGACG GACGAAGCCGGCCGGATTCAGGGAACGGGGCCTTCCGCGTCGATTCGCGAGGTTATGACCGGCAAACTGTGGTTC TTGGTTGTTGCCGGCTTCTTCTTCCTTCTGGCGAACAATGCCTACAGCAACAACTTGTCCCTGTTGGTCGAGCAG CGCGGCTTGGGCGATGCCGGAACCGCTGGACTGATTTCCACCATCGGACAGTTCGGCGGACTGCTGGCTGGTTTG TGCGTCGGTCTTATGGTCCGATTCGTGAAGAACCATTTGCTGATGGTCGGCTTCATTGTCGAGGGCCTGTCTTTG CTGCTGCTTGGCTGCTCGGCCAGCCTGCCACTGCTCATCATCGGCAGTTTCTTTGCCGGAGCCGGCCTGAGCATC TACTATGCGCAGGCGCCATTCCTCGTCACCGTCATCGAAAAGCCCTACCTCATCCCGCTGGGCATTGCTGCCATG ACCACGGCCAACGCACTGGGCGGATTTGCCAGCCCTGTGCTCGTCAACGCGATTAACGGACTGTTTGGTTCGCAC GCGGCCGGCGCGATGTTCATCGGTGCCGCGATTGCTCTGGCCGGAGCGGTGGCTCTCGGTGTGAGCGGATTCCAA AAGAAGTGCCTCGAAAGCGCGAAGTGA

[0281] 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.

[0282] SEQ ID NO: 38 MAEFHYAIGHFHCAGHRIGCSGIPGQLALQRADDCFGITLTALVGAWLTGKLASILSRKTVALIGAGGMLLFGLL PYFVHSSLAAVIAFSALMGVCLGFINNVLPTLISVHYEGDERQSIMGQQVAVASIGAMVFMTVAGKLATAQWYHA YLIYLFAAWLWCAFTLPTKNGETDEAGRIQGTGPSASIREVMTGKLWFLWAGFFFLLANNAYSNNLSLLVEQ RGLGDAGTAGLISTIGQFGGLLAGLCVGLMVRFVKNHLLMVGFIVEGLSLLLLGCSASLPLLIIGSFFAGAGLSI YYAQAPFLVTVIEKPYLIPLGIAAMTTANALGGFASPVLVNAINGLFGSHAAGAMFIGAAIALAGAVALGVSGFQ KKCLESAK

[0283] 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.

[0284] SEQ ID NO: 39 ATGGAGCGCGATGCTTTCCGGCTGCCGGGCCTCACCGCCGGCGATGACAACCAGTATGCCGATCACACGCTCACC GGCATGGCAGCCGATGCGGCGAACGTCATAGCCGCAGGCGGTCCCGCCCCGCTGACTAGCTTCGGCACTGTCGCT CAAGCCGCCCATCTCAATCCAGATGACGGCTTCGGCATCATTGGCCATGATCTTGCACACCCATCGCACCTACAC CGGCATGACTATATGGAAATCACGCACGCCATCGCCGGTACGGTACTGGTCTGGGTCGAAGGAGAGACCAACGTG CTGACACAGGGCGGCACCATACTCATCAAGCCTGGAGCCCGTCATCTCATCTCCCCCATCATCGAATACGGGCAA ACACCACACGAGGCGGACATCCTGATTAAACCCGAGCTCATCAGGCAATGCCGCATTCCGATTCTGGAAGCAGCC GGCGCCGACCGGATGTTCATTAGCTGGCTTGACGATGACCGGCAGACCCACTGCCTGCTGGCAGCCGGCAAGCAC CACGCCGGCGAGGCCGCTATCAGCCGCATGTTCATCGCCTACTGCATCAACGCAACCTACAGGCCAGACTTCACC GTCATCGGCAACCTGCTCGAGCTGTTCCACGAAACGTCCCGAGTCTTGGAACACCAGCCACGTACCGATCCGCTG ATCGCCGCCATCATCGAAACCATCACGGCAGATCCCGCCACGGCCCACAACCAGGCCATAGCGGACACACTTGGA TACAGCGTGGGATATCTGTCCCGGTACGCGCGCAAGCACAGCGGGCACACACTCGGCCAACTCATCAACGAGGAA AGGCTCCGACTCGGCGCCGAACTGCTCGTCACCACCGACGACACCATTGCCGAAATCACCCGAACCATTGGCTAC GAAAGTCCAGCCTATTTCCATAAACTCTTCCGCAGCCGCTACCTCATTACCCCCGACCGCTACCGCAACGACTTC CGTATCGCATTACGTTGCGGATGA

[0285] 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.

[0286] SEQ ID NO: 40 MERDAFRLPGLTAGDDNQYADHTLTGMAADAANVIAAGGPAPLTSFGTVAQAAHLNPDDGFGIIGHDLAHPSHLH RHDYMEITHAIAGTVLVWVEGETNVLTQGGTILIKPGARHLISPIIEYGQTPHEADILIKPELIRQCRIPILEAA GADRMFISWLDDDRQTHCLLAAGKHHAGEAAISRMFIAYCINATYRPDFTVIGNLLELFHETSRVLEHQPRTDPL IAAIIETITADPATAHNQAIADTLGYSVGYLSRYARKHSGHTLGQLINEERLRLGAELLVTTDDTIAEITRTIGY ESPAYFHKLFRSRYLITPDRYRNDFRIALRCG

[0287] Suitably, the B. longum subsp. iuvenis strain comprises a MFS transporter and an AraC family transcriptional regulator gene.

[0288] 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.

[0289] As used herein, a ‘gene cluster’ may refer to a group of genes that are located next to each other in a chromosome.

[0290] 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.

[0291] 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. 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.

[0292] 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.

[0293] 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

[0294] 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.

[0295] 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 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.

[0296] SEQ ID NO: 43 ATGGGTCTGTGGGATGTTGACAAGATCGAGTACGTCGGCCGCGCCAAAGGACCGAAGGAAGACTTCGCCTTCCAT TACTACGATGCCGACAAGGTCGTTGCCGGCAAGAAGATGAAGGATTGGCTGCGCTTCGGCGTTGCTTGGTGGCAC ACCTTCAACCAGGAACTGGTTGATCCGTTCGGCACCGGCACCGCGCACCGCCCGTACTACAAGTACACCGATCCG ATGGACCAGGCTCTGGCCAAGGTCGACTACGCCTTCGAGCTGTTCCAGAAGCTGGGCGTCGAGTACTTCTGCTTC CACGATCGTGACATCGCCCCCGAAGGCGACACCCTGCGCGAGACCAACGCCAACCTCGACAAGGTCGTTGACAAG ATCGACGAGAATATGAAGTCCACCGGTGTCAAGCTGCTGTGGAACACCTCCTCCCTGTTCACCAACCCGCGCTTC GTGTCCGGCGCCGCCACTTCTCCGTTCGCCGACATCTACGCCTACGCCGGTGGCCAGCTCAAGAAGAGCTTGGAG ATCGGCAAGCGCCTGGGCGCCGAGAACTACGTGTTCTGGGGTGGCCGCGAAGGCTACGAGAACCTGTGGAACACC GAGATGAAGCGCGAGACCGACCACATCGCCAAGTTCTTCCACATGTGCGCAGATTACGCCAAGGAAATCGGCTTT GAGGCCCAGTTCCTGATCGAGCCGAAGCCGAAGGAGCCGACGCTGCACCAGTACGACTTCGATGCCGCCACCGCC ATCGAGTTCCTGCGCAACCACGACCTGACCGACGTCTTCAAGCTGAACTTGGAAGGCAACCACGCCAACCTGGCC GGCCACACCTACCAGCACGAGATCCGCGTGGCCCGCGAGTCCGGCTTCCTCGGTTCCCTCGACGCCAACCAGGGC GACAAGCTCATCGGCTGGGATATGGACGAGTTCCCGACCGATCTGTACGAGACCGTCGCCGTCATGTGGGAAGTC CTGCAGGCCGGCTCCATCGGACCTCACGGTGGTCTGAACTTCGACGCCAAGCCGCGCCGTACCTCCTTCTACGAG GAGGACCTGTTCCGCTCCCACATCGCCGGCATGGATGCCTACGCCGCCGGCCTGCTGGTTGCCGACAAGATGAAC CAGGACGGCTTCATCCAGAATCTTCAGGCCGAGCGCTACAGCTCCTACGACTCCGGCATCGGCAAGGACATCGAC GAGGGCAACGTCACCTTGGCCGACCTCGAAGCCTACAGCCTCGACAAGCCGCAGTCCGAGCTCATCGCCGCCACC AAGTCCGATCACCTCGAGTCCGTCAAGGCCACCATCAACAACTACATCATTGATGCCCTGGCTGAGGTCGAGTGA

[0297] 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.

[0298] SEQ ID NO: 44 MGLWDVDKIEYVGRAKGPKEDFAFHYYDADKWAGKKMKDWLRFGVAWWHTFNQELVDPFGTGTAHRPYYKYTDP MDQALAKVDYAFELFQKLGVEYFCFHDRDIAPEGDTLRETNANLDKWDKIDENMKSTGVKLLWNTSSLFTNPRF VSGAATSPFADIYAYAGGQLKKSLEIGKRLGAENYVFWGGREGYENLWNTEMKRETDHIAKFFHMCADYAKEIGF EAQFLIEPKPKEPTLHQYDFDAATAIEFLRNHDLTDVFKLNLEGNHANLAGHTYQHEIRVARESGFLGSLDANQG DKLIGWDMDEFPTDLYETVAVMWEVLQAGSIGPHGGLNFDAKPRRTSFYEEDLFRSHIAGMDAYAAGLLVADKMN QDGFIQNLQAERYSSYDSGIGKDIDEGNVTLADLEAYSLDKPQSELIAATKSDHLESVKATINNYIIDALAEVE

[0299] Human milk oligosaccharide

[0300] 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.

[0301] 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.

[0302] 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.

[0303] SEQ ID NO: 45 ATGAGCAATCCAACAAATGATGGTATCAACTTGAATTACCTCGCAAACGTGCGTCCCTCGTCGCGACAGCTTGTC TGGCAGCGTATGGAGATGTATGCCTTCATACACTTCGGCATGAATACCATGACAGACAGGGAATGGGGTCTTGGG CATGAGGATCCGGCGCTGTTCGATCCACAGAATGTAGATGTGGAACAGTGGATGGATGCGCTGGTGGCTGGTGGA ATGACTGGTGTCATCTTGACGTGCAAGCATCATGATGGATTCTGCCTGTGGCCATCGCGTTACACGCAGCATACC GTTGCCGCCTCGCCGTGGAGGGACGGAAAAGGGGATCTCGTTCGTGAGGTCAGTGAGTCCGCCAGACGTCATGGA CTGAAGTTCGGCGTATACCTGTCTCCGTGGGATCGAACCGAAGAATCCTATGGCAAAGGCAAGGCATATGACGAT TTCTACGTCGGACAATTGACTGAGTTGCTCACCCAGTACGGACCGATTTTCTCCGTATGGCTGGATGGTGCCAAT GGTGAGGGCAAGAACGGCAAGACTCAGTATTACGACTGGGATCGTTACTACAACGTCATTCGTTCGCTTCAACCC AATGCGGTGATATCCGTATGCGGTCCCGACGTTCGCTGGGCTGGAAATGAAGCCGGACATGTACGTGACAACGAA TGGAGTGTCGTGCCCCGACGACTGCGTTCGGCGGAACTGACTATGGAAAATTCACAGCAGGAGGACGATGCGTCC TTTGCTTCTACGGTTCGCTCTCAAGATGACGACCTTGGAAGTCGTGAGGCGGTTTCCGGATACGGGGATGACGTC TGTTGGTACCCAGCTGAGGTCGATACCTCCATTCGCCCTGGATGGTTCTATCACAAGTATGAAGACGACAAGGTC ATGAGCGCAGATCAGCTTTTTGACCTCTGGCTTTCCGCAGTCGGCGGTAATTCGTCTCTTCTGCTCAATATTCCT CCGTCTCCAGAAGGACTGTTCGCAGAACCGGATGTGGAGTCGCTCAAGGGGCTGGGAAGCCGTATCAATGAATTC CGCAAAGCATTGGCTTCGTCTTGTTGCGAGGTCAAGACCAGCAGCGCGGACGAAACTGCAATGCGACTTCTCGAT GGGAATCAGGACACGTATTGGTCTCCTGATGCCAATGACGTGGCCCCTGCCGTCACGCTCACTTTCCCGCAGCTG ACGACGATCAATGCCGTTGTGGTTGAAGAGGCCATAGAGTATGGGCAGCGCATTGAACATATGCGCGTTACTGGT GTGCTATCTGATGGTACTGAGTGTGTACTCGGCCAGTTCGGCACAGTGGGATACCGCAGGATACTCCGCTTCGAC GATGTCGAAGTATCTTCGGTTACCCTACATGTGGATGATTCAAGGTTCACGCCAATGATCAGCCGTGCAGCTGCG GTGCGGATATAA

[0304] 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.

[0305] SEQ ID NO: 46 MSNPTNDGINLNYLANVRPSSRQLVWQRMEMYAFIHFGMNTMTDREWGLGHEDPALFDPQNVDVEQWMDALVAGG MTGVILTCKHHDGFCLWPSRYTQHTVAASPWRDGKGDLVREVSESARRHGLKFGVYLSPWDRTEESYGKGKAYDD FYVGQLTELLTQYGPIFSVWLDGANGEGKNGKTQYYDWDRYYNVIRSLQPNAVISVCGPDVRWAGNEAGHVRDNE WSWPRRLRSAELTMENSQQEDDASFASTVRSQDDDLGSREAVSGYGDDVCWYPAEVDTSIRPGWFYHKYEDDKV MSADQLFDLWLSAVGGNSSLLLNIPPSPEGLFAEPDVESLKGLGSRINEFRKALASSCCEVKTSSADETAMRLLD GNQDTYWSPDANDVAPAVTLTFPQLTTINAVWEEAIEYGQRIEHMRVTGVLSDGTECVLGQFGTVGYRRILRFD DVEVSSvtlhvddsrftpmisraaavri

[0306] 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.

[0307] 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

[0308] 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.

[0309] SEQ ID NO: 48 MKLTFDGISSCWEEGIPLGNGRMGAVLCSEPETDVLYLNDDTLWSGYPHAETSPVTPEIVAKARQASLQDDYTAA TRIIKEATLQEKDEQIYEPFGTARIQYSTPADGRESMKRQLDLARALAGETFQMGDANVHVDAWCSEPDDLLVYR MSSDAPVDVNISVAGTFLKQSRASLETVSDGHRATLWMGRMPGLNIGLLPHPSEHPWEDEQDGTGMAYAGAFSL TVTGGDINVDDNSLQCSHITGLSLRFRSMSGFKGSDQQPERSMTVIADHLEKTIDEWSTDLQTMLDRHIADYRRY FDRVAIHLGSAHDDDTELPFSAILRSDENKEPHRLEMLAEAMFDFGRYMLISSSRPHTQPANLQGIWNHKDFPNW YSAYTTNINVEMNYWMTGPCALKELIEPLVSMNEELLAPGHDAADRILGCRGSAVFHNVDLWRRALPANGDPMWA FWPFGQAWMCRNLFDEYLFNQDASYLARIWPIMRDNARFCMDFLSETEHGLAPSPATSPENCFLVNGEPVSVAQS SENATAIVRNLLDDLIQASHDLENLDEEDRNLVREAESVRSQLAETRLGADGRVLEWNDEFIESDPQHRHLSHLY ELHPGAGITSKTPRLEEAARKSLEVRGDDGSGWSIVWRMIMWARLRDAEHAKRIIGMFLRPVDANAETNLLGGGV YDSGLCAHPPFQIDGNLGFPAALSEMLVQSHDGWIRVLPALPEDWHEGSFHALRARGGIQVDATWTDQTVEYTLR CSKPTEITLNVLGTDMGRVALSPDKPFKGTIRR

[0310] Suitably, the present B. longum subsp. iuvenis may comprise a GH25 and a GH95 gene as defined herein.

[0311] HMO mixture

[0312] The composition of the invention may comprise an HMO, wherein the HMO is selected from 2'-fucosyllactose (2FL), difucosyllactose (DFL), lacto-N-tetraose (LNT), 6'-sialyllactose (6SL), 3'-sialyllactose (3SL), 3-fucosyllactose (3FL), lacto-N-neotetraose (LNnT) and any combination thereof.

[0313] The composition of the invention may comprise an HMO mixture consisting of 2'-fucosyllactose (2FL) and 3-fucosyllactose (3FL).

[0314] The composition of the invention may comprise an 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).

[0315] 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).

[0316] 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).

[0317] 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).

[0318] 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%.

[0319] 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%.

[0320] 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%.

[0321] In one embodiment, the HMO mixture comprises 6SLand 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%.

[0322] 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%.

[0323] 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%. In some embodiments, the HMO mixture consists or consists essentially of:

[0324] i. 16 wt% to 69 wt% of 2FL;

[0325] ii. 9 wt% to 24 wt% of LNT;

[0326] iii. 2 wt% to 10 wt% of DFL;

[0327] iv. 8 wt% to 26 wt% of 6SL and 3SL combined; and

[0328] v. 10 wt% to 50 wt% of 3FL.

[0329] In some preferred embodiments, the HMO mixture consists or consists essentially of:

[0330] i. 22 wt% to 59 wt% of 2FL;

[0331] ii. 12 wt% to 21 wt% of LNT;

[0332] iii. 3 wt% to 8 wt% of DFL;

[0333] iv. 11 wt% to 22 wt% of 6SL and 3SL combined; and

[0334] v. 11 wt% to 43 wt% of 3FL.

[0335] In some embodiments, the HMO mixture consists or consists essentially of:

[0336] i. 34 wt% to 85 wt% of 2FL;

[0337] ii. 10 wt% to 40 wt% of LNT;

[0338] iii. 4 wt% to 14 wt% of DFL;

[0339] iv. 9 wt% to 31 wt% of 6SL and 3SL combined; and

[0340] v. 6 wt% to 30 wt% of LNnT.

[0341] In some preferred embodiments, the HMO mixture consists or consists essentially of:

[0342] i. 40 wt% to 71 wt% of 2 FL;

[0343] ii. 12 wt% to 26 wt% of LNT;

[0344] iii. 5 wt% to 10 wt% of DFL; and

[0345] iv. 10 wt% to 28 wt% of 6SL and 3SL combined; and

[0346] v. 7 wt% to 23 wt% of LNnT.

[0347] In some embodiments, the HMO mixture consists or consists essentially of:

[0348] i. 20 wt% to 60 wt% of 2FL;

[0349] ii. 4 wt% to 30 wt% of LNT;

[0350] iii. 1 wt% to 12 wt % of DFL;

[0351] iv. 7 wt% to 23 wt% of 6SL and 3SL combined;

[0352] v. 10 wt% to 50 wt% of 3FL; and

[0353] vi. 3 wt% to 25 wt% of LNnT. In some preferred embodiments, the HMO mixture consists or consists essentially of:

[0354] i. 22 wt% to 55 wt% of 2 FL;

[0355] ii. 6 wt% to 20 wt% of LNT;

[0356] iii. 2 wt% to 8 wt % of DFL;

[0357] iv. 8 wt% to 22 wt% of 6SL and 3SL combined;

[0358] v. 13 wt% to 46 wt% of 3FL and

[0359] vi. 5 wt% to 20 wt% of LNnT.

[0360] The composition of the invention may also comprise lacto-N-fucopentaose I (LNFP-I).

[0361] 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.

[0362] 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).

[0363] 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.

[0364] In some embodiments, the HMO mixture consists or consists essentially of:

[0365] i. 20 wt% to 46 wt% of 2FL;

[0366] ii. 11 wt% to 17 wt% of LNT;

[0367] iii. 2 wt% to 7 wt% of DFL;

[0368] iv. 9 wt% to 21 wt% of 6SL and 3SL combined;

[0369] v. 9 wt% to 34 wt% of 3FL; and

[0370] vi. 5 wt% to 32 wt% of LNFP-I. In some preferred embodiments, the HMO mixture consists or consists essentially of: i. 22 wt% to 42 wt% of 2FL;

[0371] ii. 12 wt% to 15 wt% of LNT;

[0372] iii. 3 wt% to 6 wt% of DFL;

[0373] iv. 9 wt% to 19 wt% of 6SL and 3SL combined;

[0374] v. 11 wt% to 32 wt% of 3FL; and

[0375] vi. 10 wt% to 19 wt% of LNFP-I.

[0376] In some embodiments, the HMO mixture consists or consists essentially of:

[0377] i. 27 wt% to 41 wt% of 2FL;

[0378] ii. 8 wt% to 15 wt% of LNT;

[0379] iii. 4 wt% to 6 wt% of DFL;

[0380] iv. 8 wt% to 18 wt% of 6SL and 3SL combined;

[0381] v. 13 wt% to 21 wt% of LNnT; and

[0382] vi. 7 wt% to 33 wt% of LNFP-I.

[0383] In some preferred embodiments, the HMO mixture consists or consists essentially of: i. 32 wt% to 39 wt% of 2FL;

[0384] ii. 10 wt% to 14 wt% of LNT;

[0385] iii. 4 wt% to 6 wt% of DFL;

[0386] iv. 7 wt% to 15 wt% of 6SL and 3SL combined;

[0387] v. 16 wt% to 20 wt% of LNnT; and

[0388] vi. 11 wt% to 23 wt% of LNFP-I.

[0389] In some embodiments, the HMO mixture consists or consists essentially of:

[0390] i. 29 wt% to 40 wt% of 2FL;

[0391] ii. 8 wt% to 13 wt% of LNT;

[0392] iii. 3 wt% to 11 wt % of DFL;

[0393] iv. 3 wt% to 15 wt% of 6SL and 3SL combined;

[0394] v. 11 wt% to 35 wt% of 3FL;

[0395] vi. 1 wt% to 18 wt% of LNnT; and

[0396] vii. 2 wt% to 24 wt% of LNFP-I.

[0397] In some preferred embodiments, the HMO mixture consists or consists essentially of: i. 32 wt% to 39 wt% of 2FL; ii. 9 wt% to 12 wt% of LNT;

[0398] iii. 3 wt% to 11 wt % of DFL;

[0399] iv. 4 wt% to 15 wt% of 6SL and 3SL combined;

[0400] v. 12 wt% to 35 wt% of 3FL;

[0401] vi. 1 wt% to 17 wt% of LNnT; and

[0402] vii. 4 wt% to 14 wt% of LNFP-I.

[0403] 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.

[0404] 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%.

[0405] Further

[0406] The composition of the present invention may comprise at least one further probiotic. As used herein, the term “probiotic” may refer to a component that contains a sufficient number of viable microorganisms to alter the gut microbiota of the young individual (see e.g. Hill, C., et al., 2014. Nature reviews Gastroenterology & hepatology, 11(8), p.506). Suitably, the probiotic comprises a commercially available probiotic strain and / or a strain which has been shown to have health benefits (See e.g. Fijan, S., 2014. International journal of environmental research and public health, 11(5), pp.4745-4767). Exemplary probiotic microorganisms may include Bifidobacterium, Lactobacillus, Limosilactobacillus, Lacticaseibacillus, Saccharomyces, Enterococcus, Streptococcus, Pediococcus, Leuconostoc, Bacillus, and Escherichia coli.

[0407] In some embodiments, the at least one further probiotic comprises Lacticaseibacillus, Bifidobacterium, Lactobacillus, and / or Limosilactobacillus. In some preferred embodiments, the at least one further probiotic comprises Lactobacillus rhamnosus, Bifidobacterium longum and / or Bifidobacterium animalis.

[0408]

[0409] Bifidobacterium i infantis In some embodiments, the composition or combination of the invention further comprises Bifidobacterium longum subsp. infantis.

[0410] 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).

[0411] 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).

[0412] 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.

[0413] 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.

[0414] 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.

[0415] Bifidobacterium longum subsp. infantis LMG 11588 is sold by the Belgian Coordinated Collections of Microorganisms (BCCM) under the LMG accession number LMG 11588.

[0416] Bifidobacterium longum subsp. infantis ATCC 15697 is sold by the American Type Culture Collection (ATCC) under the accession number ATCC 15697. The composition or combination according to the invention may contain from 103to 1012cfu of Bifidobacterium longum subsp. infantis, more preferably from 107to 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 young individual 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 young individual in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less.

[0417] In one embodiment, the Bifidobacterium longum subsp. infantis is viable.

[0418] Bifidobacterium animalis subsp. lactis

[0419] In some embodiments, the composition or combination of the invention further comprises Bifidobacterium animalis subsp. lactis.

[0420] 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.

[0421] 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.

[0422] 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.

[0423] Bifidobacterium animalis subsp. lactis CNCM 1-3446 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 1-3446.

[0424] 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 108to 1010cfu 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 young individual 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 young individual in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less.

[0425] 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 young individual 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 young individual in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less.

[0426] In one embodiment, the Bifidobacterium animalis subsp. lactis is viable.

[0427] Bifidobacterium animalis subsp. lactis. In particularly preferred embodiments, the composition of the invention further comprises Bifidobacterium longum subsp. infantis and Bifidobacterium longum subsp. lactis.

[0428] Lactobacillus rhamnosus

[0429] In some embodiments, the at least one further probiotic comprises Lactobacillus rhamnosus. Lacticaseibacillus rhamnosus (also known as Lactobacillus rhamnosus) is a short Grampositive homofermentative facultative anaerobic non-spore-forming rod that often appears in chains. Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotic strains. Various health effects are well documented (see e.g. Segers, M. E. and Lebeer, S., 2014. Microbial cell factories, 13(1), pp.1-16). L. rhamnosus may boost endogenous production of vitamin K2, through the production of precursors.

[0430] In some embodiments, the at least one further probiotic comprises of Lactobacillus rhamnosus LPR.

[0431] Administration of probiotics The young individual may be administered any suitable amounts of probiotics, in any suitable form and via any suitable route of administration (e.g. in any form and via any route described herein).

[0432] Suitably, the one or more probiotic is administered to the young individual in a total amount of at least about 105cfu / day, at least about 106cfu / day, at least about 107cfu / day, at least about 108cfu / day, at least about 109cfu / day, or at least about 1010cfu / day. Suitably, the one or more probiotic is administered to the young individual in a total amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less. Suitably, the one or more probiotic is administered to the young individual in a total amount of from about 106cfu / day to about 1012cfu / day, from about 107cfu / day to about 1011cfu / day or from about 108cfu / day to about 1010cfu / day.

[0433] Suitably, Bifidobacterium longum (e.g. B. infantis) is administered to the young individual in an amount of at least about 105cfu / day, at least about 106cfu / day, at least about 107cfu / day, at least about 108cfu / day, at least about 109cfu / day, or at least about 1010cfu / day. Suitably, Bifidobacterium longum (e.g. B. infantis) is administered to the young individual in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less. Suitably, Bifidobacterium longum (e.g. B. infantis) is administered to the young individual in an amount of from about 106cfu / day to about 1012cfu / day, from about 107cfu / day to about 1011cfu / day or from about 108cfu / day to about 1010cfu / day.

[0434] Suitably, Bifidobacterium animalis (e.g. B. lactis) is administered to the young individual in an amount of at least about 105cfu / day, at least about 106cfu / day, at least about 107cfu / day, at least about 108cfu / day, at least about 109cfu / day, or at least about 1010cfu / day. Suitably, Bifidobacterium animalis (e.g. B. lactis) is administered to the young individual in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less. Suitably, Bifidobacterium animalis (e.g. B. lactis) is administered to the young individual in an amount of from about 106cfu / day to about 1012cfu / day, from about 107cfu / day to about 1011cfu / day or from about 108cfu / day to about 1010cfu / day.

[0435] Suitably, Lactobacillus rhamnosus is administered to the young individual in an amount of at least about 105cfu / day, at least about 106cfu / day, at least about 107cfu / day, at least about 108cfu / day, at least about 109cfu / day, or at least about 1010cfu / day. Suitably, Lactobacillus rhamnosus is administered to the young individual in an amount of about 1012cfu / day or less, about 1011cfu / day or less, or about 1010cfu / day or less. Suitably, Lactobacillus rhamnosus is administered to the young individual in an amount of from about 106cfu / day to about 1012 cfu / day, from about 107cfu / day to about 1011cfu / day or from about 108cfu / day to about 1010cfu / day.

[0436] Prebiotics

[0437] In some embodiments, the composition of the invention may comprise at least one further prebiotic (i.e. in addition to the HMO mixture as described herein). Suitably, the prebiotic is a glycan substrate.

[0438] Suitably, the glycan substrate may comprise or consist of pectin, arabinogalactan and / or starch.

[0439] Suitably, the glycan substrate may comprise or consist of pectin.

[0440] Suitably, the glycan substrate may comprise or consist of arabinogalactan.

[0441] Suitably, the glycan substrate may comprise or consist of starch.

[0442] In a particularly preferred embodiment, the glycan substrate may comprise or consist of arabinan.

[0443] Suitably, the glycan substrate is provided in the form of a dietary fiber. For example, the dietary fiber may be a prebiotic fiber.

[0444] Suitably, the glycan substrate may be comprised in an ingredient, for example a dietary ingredient.

[0445] The ingredient containing one or several glycan substrates may be selected from the group consisting of purified polysaccharide or purified oligosaccharide, a dietary fiber ingredient, a semi-purified food ingredient, a raw food ingredient, a food additive, a HMO, a semi-purified or purified peptido-glycan.

[0446] The semi-purified food ingredient may be a fruit, vegetable or cereal extract.

[0447] The raw food ingredient may be a fruit, vegetable, cereal, algae or microalgae.

[0448] The food additive may be a guar gum or gum arabic.

[0449] Suitably, the peptide-glycan may be a GAG.

[0450] Suitably, the glycan substrate may be comprised in a purified fiber. The pectin may be comprised in fruit or vegetable pectin. Accordingly, suitable ingredients comprising pectin include, but are not limited to, fruits (e.g., apple, pear), vegetables, legumes (peas), and roots (e.g., sugar beet). Suitable purified fibers comprising arabinogalactan include peach pectin. Suitably, the pectin extracted from sugar beet contains arabinan, galactans and arabinogalactans and may be provided as an ingredient.

[0451] The arabinogalactan may be comprised in fruit or vegetable pectin. Illustrative suitable ingredients comprising arabinogalactan include, but are not limited to, fruits, vegetables, whole grain cereals and sea weed dietary fiber. Suitable purified fibers comprising arabinogalactan include peach pectin, larch wood arabinogalactan, and Arabic gum. Suitably, the arabinogalactan may be provided in larch wood arabinogalactan.

[0452] The starch may be comprised in resistant-starch from cereals (whole grains), legumes, vegetables (e.g., corn) and roots (e.g., potato). Illustrative suitable ingredients comprising starch include, but are not limited to, corn. Suitable purified fibers comprising starch include high amylose starch and resistant dextrin. Suitably, the starch may be provided in a potato, corn or other ingredient. Suitably, the starch may be comprised in a potato ingredient.

[0453] Human milk oligosaccharide (HMO)

[0454] Suitably, the prebiotic comprises one or more additional HMO(s). Suitably, the additional HMO(s) is / are different to those provided in the HMO mixture as described herein.

[0455] Suitably, the additional HMO(s) is / are capable of being metabolized by the B longum subsp. iuvenis microorganism. Suitably, the additional HMO(s) may be capable of promoting growth and / or survival of the B. longum subsp. iuvenis. HMOs capable of promoting growth and / or survival of the B. longum subsp. iuvenis may be determined by e.g. anaerobic culture of the B. longum subsp. iuvenis with the HMO to be tested. Growth and / or survival of the B. longum subsp. iuvenis may be determined by measuring bacteria cell number, cell density (e.g. measured by optical density) and / or the abundance of 16S rDNA - for example using PCR methods. An HMO capable of promoting growth and / or survival of the B. longum subsp. iuvenis may increase the number of B. longum subsp. iuvenis bacteria in an anaerobic culture by at least 20%, at least 30%, at least 40%, at least 50%, at least 75% or at least 100% compared to the number of B. longum subsp. iuvenis bacteria in a control anaerobic culture which does not comprise the HMO. Suitably, an HMO capable of promoting growth and / or survival of the B. longum subsp. iuvenis may increase the number of B. longum subsp. iuvenis bacteria in an anaerobic culture by a statistically significant amount (e.g. p-value <0.05 as determined by one-way ANOVA) compared to the number of B. longum subsp. iuvenis bacteria in a control anaerobic culture which does not comprise the HMO. The HMO may be a fucosylated oligosaccharide (i.e. an oligosaccharide having a fucose residue; e.g. 3-fucosyllactose (3-FL), difucosyllactose (DiFL), lacto-N-fucopentaose (e.g. lacto-N-fucopentaose I, 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 and any combination thereof), an N-acetylated oligosaccharide (e.g. para-lacto-N-neohexaose (para-LNnH), LNnT (lacto-N-neotetraose), DSLNT (disialyllacto-N-tetraose), 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 and any combinations thereof) and / or a sialylated oligosaccharide (e.g. Lst (sialyllacto-N-tetraose), Lst-a, Lst-b or Lst-c)).

[0456]

[0457] The composition can be any type of composition, such as a composition in the form of a food or beverage product, a nutritional supplement for human, or a pharmaceutical composition. The composition may be in solid (e.g. powder), liquid or semi-liquid form. The composition may be in the form of a food composition, a beverage, a nutritional formula, a nutritional supplement, or a nutraceutical.

[0458] Food and beverage products include all products intended to be consumed orally by human beings, for the purpose of providing nutrition and / or pleasure. It can for example be a nutritional composition, such as for young children. Examples of food and beverage products include dairy products such as milk products or yogurts, soups, sauces, sweet and savoury snacks, powdered drinks and cereal products.

[0459] In some embodiments, the composition is in the form of a nutritional composition, a medical food product for clinical nutrition, a growing-up milk, or a supplement.

[0460] In a further embodiment, the invention provides the use of a composition of the invention for the manufacture of a medicament for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual, wherein the composition comprises Bifidobacterium longum subsp. iuvenis.

[0461] In some embodiments, the composition is in the form of a nutritional composition. As used herein, a “nutritional composition” may mean a composition which nourishes a young individual. This nutritional composition is usually to be taken orally or intravenously, and typically includes a lipid or fat source and a protein source. In some embodiments, the composition is in the form of a medical food product for clinical nutrition. As used herein, a ’’medical food product for clinical nutrition” may also be known as a “Food for Special Medical Purposes (FSMP)” and refer to specialised foods designed to help meet the nutritional or dietary needs of young individuals living with a disease, disorder or medical condition who are temporarily or permanently unable to achieve an adequate nutritional intake from normal foods or through modification of the normal diet.

[0462] In another embodiment, the composition is in the form of a pharmaceutical product. Pharmaceutical products include for example drops, syrups, powder, tablet or capsule products intended to treat of prevent an adverse medical condition in a young individual in need thereof.

[0463] The composition can also be in the form of an animal food product or a nutritional supplement for animals. Preferably, the animal is a mammal. Examples of animals include primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, fish, birds and the like.

[0464] Nutritional composition

[0465] 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, 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.

[0466] 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.

[0467] 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 infant, young child or child.

[0468] When the nutritional composition is a supplement, it may comprise the Bifidobacterium longum subsp. iuvenis, optionally the Bifidobacterium longum subsp. infantis, and / or Bifidobacterium animalis subsp. lactis, and / or the HMO mixture as described herein, and no other additional nutrient on top of the excipients necessary to obtain a stable nutritional composition. 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.

[0469] 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.

[0470] Other ingredients

[0471] The composition according to the present invention may also comprise any other suitable ingredients.

[0472] Suitably, the composition 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), fructooligosaccharides (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 can also contain at least one BMO (bovine milk derived oligosaccharide).

[0473] In some embodiments, the composition according to the invention comprises at least one additional HMO.

[0474] In other embodiments, the composition 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.

[0475] In some embodiments, the composition of the present invention does not comprise at least one further probiotic (or probiotic strain), such as at least one further probiotic bacterial strain. In other embodiments, the composition of the present invention can further comprise at least one further probiotic (or probiotic strain), such as at least one further probiotic bacterial strain.

[0476] 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.

[0477] The nutritional composition 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.

[0478] 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.

[0479] 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%).

[0480] 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.

[0481] 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.

[0482] 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.

[0483] 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).

[0484] The protein component can alternatively be replaced by a mixture or synthetic amino acid, for example for preterm or low birth weight infants.

[0485] 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.

[0486] The nutritional composition according to the present invention generally contains a carbohydrate source. This is particularly preferable in the case where the nutritional composition 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.

[0487] 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.

[0488] 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.

[0489] 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.

[0490] The nutritional composition of the invention may also contain other substances which may have a beneficial effect such as nucleotides, nucleosides, and the like.

[0491] 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.

[0492] Manufacture of a nutritional composition

[0493] The nutritional composition according to the invention may be prepared in any suitable manner. A composition will now be described by way of example.

[0494] 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.

[0495] 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.

[0496] The liquid mixture is then homogenised, for example in two stages. 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.

[0497] 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.

[0498] 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.

[0499] 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.

[0500] In another embodiment, the composition of the invention may be a supplement such as a paediatric 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.

[0501] 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.

[0502] 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.

[0503] 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.

[0504] 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.

[0505] 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.

[0506] 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.

[0507] 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.

[0508] 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.

[0509] Oligosaccharide mixture

[0510] A nutritional composition (e.g. growing-up milk) according to the invention may contain any suitable amounts of oligosaccharides.

[0511] Suitably, the nutritional composition comprises the oligosaccharide mixture in a total amount of at least about 0.5 wt%, at least about 1 wt%, or at least about 2 wt%, on a dry weight basis. Suitably, the nutritional composition comprises the oligosaccharide mixture in a total amount of about 10 wt% or less, about 8 wt% or less or about 5 wt% or less, on a dry weight basis. Suitably, the nutritional composition comprises the oligosaccharide mixture in a total amount of from about 0.5 wt% to about 10 wt%, about 1 wt% to about 8 wt%, or about 2 wt% to about 5 wt%, on a dry weight basis.

[0512] Suitably, the nutritional composition comprises BMOs in a total amount of at least about 0.5 wt%, at least about 1 wt%, or at least about 2 wt%, on a dry weight basis. Suitably, the nutritional composition comprises BMOs in a total amount of about 10 wt% or less, about 8 wt% or less or about 5 wt% or less, on a dry weight basis. Suitably, the nutritional composition comprises BMOs in a total amount of from about 0.5 wt% to about 10 wt%, about 1 wt% to about 8 wt%, or about 2 wt% to about 5 wt%, on a dry weight basis.

[0513] Probiotics

[0514] A nutritional composition (e.g. growing-up milk) according to the invention may contain any suitable amounts of probiotic.

[0515] Suitably, the nutritional composition comprises the one or more probiotic in a total amount of at least about 105cfu / 100g, at least about 106cfu / 100g, at least about 107cfu / 100g, or at least about 108cfu / 100g, at least about 109cfu / 100g, or at least about 101° cfu / 100g on a dry weight basis. Suitably, the nutritional composition comprises the one or more probiotic in a total amount of about 1012cfu / 100g or less, about 1011cfu / 100g or less, about 1O10cfu / 100g or less, on a dry weight basis. Suitably, the nutritional composition comprises the one or more probiotic in a total amount of about 106cfu / 100g to about 1012cfu / 100g, about 107cfu / 100g to about 1011cfu / 100g, or about 108cfu / 100g to about 101° cfu / 100g, on a dry weight basis.

[0516] Suitably, the nutritional composition comprises Lactobacillus rhamnosus in an amount of at least about 105cfu / 100g, at least about 106cfu / 100g, at least about 107cfu / 100g, or at least about 108cfu / 100g, at least about 109cfu / 100g, or at least about 101° cfu / 100g on a dry weight basis. Suitably, the nutritional composition comprises Lactobacillus rhamnosus in an amount of about 1012cfu / 100g or less, about 1011cfu / 100g or less, about 101° cfu / 100g or less, on a dry weight basis. Suitably, the nutritional composition comprises Lactobacillus rhamnosus in an amount of about 106cfu / 100g to about 1012cfu / 100g, about 107cfu / 100g to about 1011cfu / 100g, or about 108cfu / 100g to about 101° cfu / 100g, on a dry weight basis.

[0517] In a preferred embodiment, the nutritional composition comprises Bifidobacterium longum (e.g. B. infant! s) in an amount of at least about 105cfu / 100g, at least about 106cfu / 100g, at least about 107cfu / 100g, or at least about 108cfu / 100g, at least about 109cfu / 100g, or at least about 101° cfu / 100g on a dry weight basis. Suitably, the nutritional composition comprises Bifidobacterium longum (e.g. B. in fa nt is) in an amount of about 1012cfu / 100g or less, about 1011cfu / 100g or less, about 101° cfu / 100g or less, on a dry weight basis. Suitably, the nutritional composition comprises Bifidobacterium longum (e.g. B. infantis) in an amount of about 106cfu / 100g to about 1012cfu / 100g, about 107cfu / 100g to about 1011cfu / 100g, or about 108cfu / 100g to about 101° cfu / 100g, on a dry weight basis.

[0518] In a preferred embodiment, the nutritional composition comprises Bifidobacterium animalis (e.g. B. lactis) in an amount of at least about 105cfu / 100g, at least about 106cfu / 100g, at least about 107cfu / 100g, or at least about 108cfu / 100g, at least about 109cfu / 100g, or at least about 101° cfu / 100g on a dry weight basis. Suitably, the nutritional composition comprises Bifidobacterium animalis (e.g. B. lactis) in an amount of about 1012cfu / 100g or less, about 1011cfu / 100g or less, about 101° cfu / 100g or less, on a dry weight basis. Suitably, the nutritional composition comprises Bifidobacterium animalis (e.g. B. lactis) in an amount of about 106cfu / 100g to about 1012cfu / 100g, about 107cfu / 100g to about 1011cfu / 100g, or about 108cfu / 100g to about 101° cfu / 100g, on a dry weight basis.

[0519] In a particulally preferred embodiment, the nutritional composition comprises Bifidobacterium longum (e.g. B. infantis) and Bifidobacterium animalis (e.g. B. lactis) in an amount of at least about 105cfu / 100g, at least about 106cfu / 100g, at least about 107cfu / 100g, or at least about 108cfu / 100g, at least about 109cfu / 100g, or at least about 101° cfu / 100g on a dry weight basis. Suitably, the nutritional composition comprises Bifidobacterium animalis (e.g. B. lactis) in an amount of about 1012cfu / 100g or less, about 1011cfu / 100g or less, about 101° cfu / 100g or less, on a dry weight basis. Suitably, the nutritional composition comprises Bifidobacterium animalis (e.g. B. lactis) in an amount of about 106cfu / 100g to about 1012cfu / 100g, about 107cfu / 100g to about 1011cfu / 100g, or about 108cfu / 100g to about 101° cfu / 100g, on a dry weight basis.

[0520] Protein

[0521] A nutritional composition (e.g. growing-up milk) according to the invention may contain a protein source. This is particularly preferable in the case where a nutritional composition of the invention is a growing-up milk. The protein may be in an amount of from about 1g to about 4g per 100 kcal, or about 1.5g to about 3g per 100 kcal.

[0522] Protein sources based on, for example, whey, casein and mixtures thereof may be used as well as plant based protein sources, for example, 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. In some embodiments the protein source is whey predominant (i.e. more than 50% of proteins are coming from whey proteins, such as 60%> or70%>). 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.

[0523] 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.

[0524] The proteins may be either fully or partially hydrolysed. 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%> by weight of lysine; for example about 7% by weight of lysine which greatly improves the nutritional quality of the protein source. In one particular embodiment, the proteins of the composition are hydrolysed, fully hydrolysed or partially hydrolysed. The degree of hydrolysis (DH) of the protein can be between 2 and 20, or between 8 and 40, or between 20 and 60 or between 20 and 80 or more than 10, 20, 40, 60, 80 or 90.

[0525] At least 70%, 80%, 85%, 90%, 95% or 97% of the proteins may be hydrolysed. In a particular embodiment, 100% of the proteins are hydrolysed.

[0526] In one particular embodiment, the proteins of the composition are plant based protein.

[0527] Carbohydrate

[0528] A nutritional composition (e.g. growing-up milk) according to the present invention may contain a carbohydrate source. This is particularly preferable in the case where a nutritional composition of the invention is a growing-up milk. The carbohydrate may be in an amount of from about 5g to about 20g per 100 kcal, or about 10g to about 15g per 100 kcal.

[0529] Any carbohydrate source conventionally found in growing-up milk such as lactose, sucrose, saccharose, maltodextrin, starch and mixtures thereof may be used although one of the preferred sources of carbohydrates for growing-up milk is lactose.

[0530] Lipid

[0531] A nutritional composition (e.g. growing-up milk) according to the present invention may contain lipids and essential fatty acids. This is particularly preferable in the case where a nutritional composition of the invention is a growing-up milk. The lipids may be in an amount of from about 1g to about 10g per 100 kcal, or about 2g to about 6g per 100 kcal.

[0532] Non-limiting examples of lipids include: palm olein, high oleic sunflower oil, high oleic safflower oil, canola oil, fish oil, coconut oil, bovine milk fat, and combinations thereof. It may be particularly beneficial if the composition comprises fat in an amount of about 25 to about 30g / 100g dry weight of the composition. Non-limiting examples of essential fatty acids include: linoleic acid (LA), a-linolenic acid (ALA). Compositions of the invention may further contain gangliosides monosialoganglioside-3 (GM3) and disialogangliosides 3 (GD3), and combinations thereof.

[0533] Other components

[0534] A nutritional composition (e.g. growing-up milk) 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 B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin E, vitamin C, 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, a nutritional composition of the invention may contain emulsifiers and stabilisers such as soy, lecithin, citric acid esters of mono- and diglycerides, and the like.

[0535] A nutritional composition (e.g. growing-up milk) of the invention may also contain other substances which may have a beneficial effect, especially on bone health or bone development, such as lactoferrin, osteopontin, TGFbeta, slgA, glutamine, nucleotides, nucleosides, and the like.

[0536] Preparation of compositions

[0537] The compositions according to the present invention may be prepared by any known or otherwise suitable manner. For example, a nutritional composition, e.g. a growing-up milk, may be proposed by blending together a source of protein with a carbohydrate source and a lipid source in appropriate proportions. If used, emulsifiers may be included at this stage. Vitamins and minerals may be added at this stage, but may also be added later to avoid thermal degradation. Water, preferably water which has been subjected to reverse osmosis or deionized water, may then be added and mixed in to form a liquid mixture. The temperature of mixing is preferably room temperature, but may also be higher. The liquid mixture may then be thermally treated to reduce bacterial loads. The mixture may then be homogenized.

[0538] If it is desired to produce a powdered composition, the homogenized mixture is dried in a suitable drying apparatus, such as a spray drier or freeze drier and converted into powder.

[0539] Processes used in the manufacture of formula are based on the concept that the products must be nutritionally adequate and microbiologically safe to consume. Thus, steps that eliminate or restrict microbiological growth are central to production processes. The processing technology for each specific formula is proprietary to the manufacturer but, in general, it involves the preservation of an oil-in-water (o / w) emulsion by dehydration in the case of powder products or, sterilization in the case of ready-to-feed or concentrated liquid products. Powdered formula may be produced using various processes, such as dry blending dehydrated ingredients to constitute a uniform formula or hydrating and wet-mixing a mixture of macro-ingredients, such as fat, protein and carbohydrate ingredients and then evaporating and spray drying the resultant mixture. A combination of the two processes described above may be used where a base powder is first produced by wet-mixing and spray drying all or some of the macro-ingredients and then dry blending the remaining ingredients, including carbohydrate, minerals and vitamins and other micronutrients, to create a final formula. Liquid formulae are available in a ready-to-feed format or as a concentrated liquid, which requires dilution, normally 1:1, with water. The manufacturing processes used for these products are similar to those used in the manufacture of recombined milk.

[0540] If it is desired to produce a liquid formula, the homogenized mixture may be filled into suitable containers, preferably aseptically. However, the liquid composition may also be retorted in the container, suitable apparatus for carrying out the filling and retorting of this nature is commercially available.

[0541] Young individual

[0542] The young individual is a juvenile mammal, an infant, a young child or a child.

[0543] In some embodiments, the young individual is a juvenile mammal.

[0544] The term “juvenile mammal” may refer to a non-human mammal that has not yet reached adulthood.

[0545] In some embodiments, the composition according to the invention is for use in infants, young children or children.

[0546] In one embodiment, the young individual is an infant. In one embodiment, the young individual is a young child. In one embodiment, the young individual is a child.

[0547] In preferred embodiments, the young individual is an infant, young child or a child. The term "infant" means a child under the age of 12 months, "young child" means a child aged between one and three years, also called toddler, and “child” means a child aged between three and twelve years. Preferably, the term “child” means a child aged between three and six years.

[0548] In preferred embodiments, the young individual is an infant or a young child.

[0549] In preferred embodiments, the young individual is about 1 years of age or older. For example, the young individual may be about 12 months of age or older, about 18 months of age or older, or about 24 months of age or older. In preferred embodiments, the young individual is about 3 years of age or younger. For example, the young individual may be about 36 months of age or younger, about 30 months of age to about 24 months of age or younger.

[0550] In other preferred embodiments, the young individual is about 1 year to about 3 years of age. For example, the young individual may be about 12 months of age to about 36 months of age, about 18 months of age to about 36 months of age, or about 24 months of age to about 36 months of age. For example, the young individual may be about 12 months of age to about 36 months of age, about 12 months of age to about 30 months of age, or about 12 months of age to about 24 months of age.

[0551] The present invention is particularly suitable for children who were born preterm or with low-birth weight or experienced intra-uterine growth retardation or who suffered from growth stunting because of malnutrition or experienced disease such as Crohn’s disease and / or celiac disease and / or cancer or who were treated with drugs leading to malabsorption, anorexia and / or metabolic bone disease, such as chemotherapy drugs and / or corticosteroids. The present invention is particularly preferred for use in children who were born preterm or with low-birth weight or experienced intra-uterine growth retardation, or with intra-uterine malnutrition or who suffered growth delay. The present invention is also suitable for children at risk of bone disease, having a family history of bone disease, or having already experienced at least one, preferably several, episode(s) of fracture.

[0552] In some embodiments, the young individual suffered from and / or is suffering from stunted growth. The definition of stunting may refer to the "height for age" value to be less than two standard deviations of the WHO Child Growth Standards median (see e.g. De Onis, M. and Branca, F., 2016. Maternal & child nutrition, 12, pp.12-26).

[0553] In some embodiments, the young individual suffered from and / or is suffering from faltering growth. The term “faltering growth” may describe a pattern of slower weight gain than expected for age and sex in children and other adolescents (see e.g. King, C. and Davis, T., 2010. European journal of clinical nutrition, 64(1), pp. S11-S13). In some embodiments, the young individual suffered from and / or is suffering from growth stunting and / or faltering growth because of malnutrition or experienced disease such as anorexia, Crohn’s disease and / or celiac disease. In some embodiments, the young individual suffered from and / or is suffering from growth stunting and / or faltering growth because of treatment with drugs leading to malabsorption, anorexia and / or metabolic bone disease, such as chemotherapy drugs and / or corticosteroids. In some embodiments, the young individual was born preterm or with low-birth weight or experienced intra-uterine growth retardation. The term “preterm infant” may refer to an infant born at least than 37 weeks gestational age. The term “low birth weight infant” may refer to an infant having a live-born weight less than 2,500 g.

[0554] Methods for enhancing bone growth and / or bone strength

[0555] In an embodiment of the present invention, a composition comprising B. longum subsp. iuvenis may be used in a method for promoting bone growth, enhancing bone growth and / or bone strength.

[0556] Within the context of the present invention, the term “enhancing bone growth and / or bone strength” may refer to, in particular, one or more of the following physiological processes: bone catch-up growth, bone mass acguisition, 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.

[0557] 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), 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 bone volume fraction (BV / TV), cortical bone volume (Ct. BV), and bone ultimate force (FMax). Suitable methods to determine these parameters will be available to the skilled person.

[0558] Methods for promoting catch-up growth

[0559] A composition comprising B. longum subsp. iuvenis, in a therapeutically effective amount, may thereby promote catch-up growth. As used herein, “catch-up growth” may refer to height velocity (Growth 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.

[0560] Suitable method 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).

[0561] 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).

[0562] Within the context of the present invention, the term “promoting” indicates a factor or a number of factors causing a certain process to occur.

[0563] EXAMPLES

[0564] The invention is further described with reference to the following examples. It will be appreciated that the invention as claimed is not intended to be limited in any way by these examples.

[0565] Unless otherwise indicated, statistical analysis was performed using One-way ANOVA followed by a Dunnett's multiple comparisons test. *p<0.05.

[0566] Example 1 - Impact of Bifidobacterium longum subsp. iuvenis or Bifidobacterium longum subsp. infantis combined with arabinan on vitamin K2 (MK-7) production in a gut model

[0567] Tube based fermentation system is a method for comparing several conditions or many ingredients at the same time. Tubes were filled with a mix media + 5g of fibers, human stool and a Bifidobacteria's supplement of 5E07 CFU / ml.

[0568] Three timepoints collections samples were collected during the fermentation to analyse the growth of the Bifidobacteria, NMR, LCMS and GCMS effects.

[0569] Tube-based fermentation was performed over 48 hours. The following groups were evaluated: arabinan, arabinan + Bifidobacterium longum subsp. iuvenis (CNCM I-5685, strain a), arabinan + Bifidobacterium longum subsp. iuvenis (CNCM I-5687, strain b), arabinan + Bifidobacterium longum subsp. infantis (LGM11588).

[0570] It can be seen as shown in Figure 1 that Bifidobacterium longum subsp. iuvenis (CNCM I-5685) + arabinan promoted vitamin K2 production on top of the effect of arabinan alone, while the other Bifidobacterium longum subsp. iuvenis (CNCM I-5687) and Bifidobacterium longum subsp. infantis (LGM11588) showed a trend of increasing vitamin K2 production on top of the effect of arabinan alone.

[0571] Example 2 - Preclinical model to test efficacy of Bifidobacterium longum subsp. iuvenis

[0572] An in-vivo preclinical model was developed, as shown in Figure 2. Neonatal animals were derived from C57BL / 6 WT breeding pairs either under a no fiber diet and maintained with no fiber diet (Group 2), or from breeding pairs under a diet containing fibers (4.7% fiber) (Group 1). To test the impact of different nutritional interventions, animals were supplemented from postnatal day 5 (PND5) by gavage with different nutritional blends.

[0573] C57BL / 6 WT pups received different combinations of nutritional ingredients, Group 3 (6HMOs + 2 bifidobacterial strains (B. infantis LGM11588 and B. lactis CNCM 1-3446); Group 46HMOs + 3 bifidobacterial strains (8. infantis LGM11588 and 8. lactis CNCM 1-3446 and 8. / . iuvenis CNCM I-5942), Group 5 (2HMOs + 3 bifidobacterial strains (8. infantis LGM11588 and B. lactis CNCM 1-3446 and B. / . iuvenis CNCM I-5942)) via oral gavage while being nursed by mothers fed on no fiber diet. At postnatal day (PND) 16, all mice were put under broad spectrum for a period of 10 days during which animals were weaned at postnatal day 21 (PND21) coupled with the introduction of fibers. Following weaning on postnatal day 21 (PND21), a selective fiber mix (adapted to 8. longum transitional strain) was introduced in the diet of these mice coupled with oral gavage of the same nutritional ingredients (reduced dose of HMOs + bifidobacterial strains). Control groups were nursed by mothers fed either with a no fiber diet only or with a high fiber diet only before weaning and kept on the same diet after weaning. The HMO mixtures used in the pre-weaning and post-weaning stages are shown in Table 1. The 2 HMOs were 2’FL and 3FL only.

[0574] The amount of 2’FL and 3FL are exactly the same between the 6 and 2 HMO groups.

[0575] Table 1 -6 HMO mixture used in the study HMO Amount for pre-weaning Amount for post-weaning stage (before d21) (pg) stage (after d21) (pg)

[0576] 2’-FL 871 264

[0577] LDFT 121 37

[0578] 3FL 240 264

[0579] LNT 290 150

[0580] 3SL 106 106

[0581] 6SL 145 47

[0582] Total HMOs 1773 868

[0583]

[0584] Animals were infected with pneumonia virus of mice at PDN35 with bone analyses performed at 10 days post infection at postnatal day 45 (PDN45).

[0585] Example 3 - Bifidobacterium longum subsp. iuvenis combined with B. infantis, B. lactis and HMO blend improves trabecular bone thickness in rodents

[0586] A preclinical experimental setup was followed as shown in Figure 2 and described in Example 2.

[0587] Micro-computed tomography (pCT LICT35, Scanco Medical AG, Basserdorf, Switzerland) was used to assess trabecular microstructure at distal metaphysis of femurs, as previously described (N. Bonnet, J. Brun, J. C. Rousseau, L. T. Duong, S. L. Ferrari, Cathepsin K Controls Cortical Bone Formation by Degrading Periostin, J. Bone Miner. Res., 2017, 32(7):1432-1441). Briefly, trabecular bone region was evaluated using isotropic 6 pm voxels. To eliminate the primary spongiosa, 30 slices of bone under the distal growth plate were not considered. The 80 slices of secondary spongiosa directly below were analyzed. Morphometric variables were computed from binarized images using direct, three-dimensional techniques that do not rely on prior assumptions about the underlying structure (N. Bonnet, N. Laroche, L. Vico, E. Dolleans, D. Courteix, C. L. Benhamou, Assessment of trabecular bone microarchitecture by two different x-ray microcomputed tomographs: a comparative study of the rat distal tibia using Skyscan and Scanco devices, Med. Phys., 2009, 36(4): 1286-97). The BV / TV fraction (%) and trabecular thickness (Tb. Th)were assessed. As can be seen in Figure 3 A& B, the assessment of trabecular bone at distal metaphysis showed that the 3 nutritional interventions had a positive impact of bone microstructure. “6HMOs + B.infantis + B. lactis + B. iuvenis” blend led to a more improved BV / TV and trabecular thickness than the “2HMOs + B.infantis + B. lactis + B. iuvenis” blend, highlighting the importance of the 4 extra HMOs (LDFT, LNT, 3’SL and 6’SL) to optimize the impact on bone thickness.

[0588] Having a higher BV / TV (that indicates a better bone volume according to the total tissue volume) and a higher Tb. Th (that indicates thicker trabeculae) indicates having improved bone thickness which can ultimately lead to stronger bone (improved bone strength).

[0589] Statistical analysis was performed using one-way ANOVA followed by a Sidak's multiple comparisons test. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

[0590] Figure 3C demonstrates the location of the sample taken (distal metaphysis).

[0591] Example 4 - Bifidobacterium longum subsp. iuvenis combined with B. infantis, B. lactis and HMO blend improves cortical bone thickness in rodents

[0592] As before, the preclinical experimental setup was followed as shown in Figure 2 and described in Example 2.

[0593] Micro-computed tomography (pCT LICT35, Scanco Medical AG, Basserdorf, Switzerland) was used to assess cortical microstructure at midshaft diaphysis of femurs, as previously described (N. Bonnet, J. Brun, J. C. Rousseau, L. T. Duong, S. L. Ferrari, Cathepsin K Controls Cortical Bone Formation by Degrading Periostin, J. Bone Miner. Res., 2017, 32(7):1432-1441). Briefly, cortical bone region was evaluated using isotropic 6 pm voxels. Femoral cortical structure was assessed using 60 continuous CT slides located at the femur midshaft. Morphometric variables were computed from binarized images using direct, three-dimensional techniques that do not rely on prior assumptions about the underlying structure (N. Bonnet, N. Laroche, L. Vico, E. Dolleans, D. Courteix, C. L. Benhamou, Assessment of trabecular bone microarchitecture by two different x-ray microcomputed tomographs: a comparative study of the rat distal tibia using Skyscan and Scanco devices, Med. Phys., 2009, 36(4): 1286-97). Cortical BV / TV fraction (%) and cortical bone mineral density (Ct. BMD) were assessed. As can be seen in Figure 4 A& B, the assessment of cortical bone at femur midshaft showed that the 3 nutritional interventions had a positive impact on bone microstructure. “6HMOs + B.infantis + B. lactis + B. iuvenis” blend led to a better BV / TV than the “6HMOs + B.infantis + B. lactis” blend, highlighting the importance of B. iuvenis to optimize the impact on bone thickness. Having a higher cortical BV / TV (that indicates a better bone volume according to the total tissue volume) and a higher cortical bone mineral density (that indicates more dense bones indicates having improved bone thickness which can ultimately lead to stronger bone (improved bone strength).

[0594] Statistical analysis was performed using a one-way ANOVA followed by a Sidak's multiple comparisons test. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

[0595] Figure 4C demonstrates the location of the sample taken (midshaft diaphysis).

[0596] Example 5 - Pearson correlation coefficients between the Somalogic protein levels against respective group average of bone readout

[0597] The Pearson correlation coefficients between the Somalogic protein levels (averaged for each group) against respective group average of bone readout: A) Cortical (BV / TV), B) Cortical BMD [mg HA / ccm], C) Trabecular BV / TV and D) Trabecular Thickness (Tb. Th [mm]). Pearson correlation coefficients were computed between the group average of Somalogic protein levels and the corresponding group average of bone readouts. The top 5 positive and top 5 negative correlations were selected for inclusion in Table 2 for each readout.

[0598] As can be seen from Table 2, with a positive Pearson correlation higher than 0.99, Roundabout homolog 2 and Antithrombin-Ill are exemplary hits showing the impact of these proteins on bone thickness read-outs.

[0599] The inverse is also true, with many negative correlations higher than 0.99, Corticosteroid 11- beta-dehydrogenase isozyme 1, Monocyte differentiation antigen CD14 soluble, Peroxi redoxin-5 mitochondrial, Tumor necrosis factor ligand superfamily member 10, Sialidase-1, Cystatin-D, Carbonic anhydrase 3, Fibronectin Fragment 4, Fibronectin, Microtubule-associated protein tau and HLA class I histocompatibility antigen alpha chain G, are exemplary hits showing the impact of these proteins on bone thickness read-outs.

[0600] Table 2:

[0601] D) Trabecular Thickness A) Cortical BV / TV B) Cortical BMD (mg. HA.ccm) C) Trabecular BV / TV

[0602] (Tb. Th. mm.)

[0603] Protein R Protein R Protein R Protein R Top positive correlations Top positive correlations Top positive correlations Top positive correlations Collagen alpha-l(l) Nectin-1, isoform Roundabout

[0604] chain: C-term 0.97 HCE004359 0.97 0.99 gamma: Extracellular 0.98 homolog2

[0605] propeptide domain

[0606]

[0607] Fibroblast growth B9 domain-containing C3a anaphylatoxin des 0.96 0.96 Antithrombin-Ill 0.99 0.98 factor receptor 1 protein 2 Arginine

[0608] Nectin-1, isoform Neurogenic locus

[0609] MTHFD2, Collagen alpha-l(l) gamma: Extracellular 0.95 0.92 notch homolog 0.97 0.95 mitochondrial chain: C-term propeptide domain protein 1

[0610] Muscle, skeletal receptor

[0611] HCE000414 0.94 0.90 Cerebellin-2 0.97 HCE000414 0.95 tyrosine-protein kinase

[0612] 72 kDa type IV Fibroblast growth factor Collagen Type II 0.94 Interferon beta 0.89 0.97 0.95 collagenase receptor 1

[0613] Top negative correlations Top negative correlations Top negative correlations Top negative correlations Corticosteroid 11- Nicotinamide

[0614] beta-dehydrogenase -1.00 -0.97 Sialidase-1 -0.99 Fibronectin Fragment 4 -1.00 phosphoribosyltransferase

[0615] isozyme 1

[0616] Monocyte

[0617] differentiation antigen -1.00 Annexin A3 -0.96 Cystatin-D -0.99 Fibronectin -1.00 CD14, soluble

[0618] Peroxi redoxin-5, T-cell surface glycoprotein Carbonic Microtubule-associated -1.00 -0.96 -0.99 -1.00 mitochondrial CD3 zeta chain anhydrase3 protein tau

[0619] Tumor necrosis

[0620] Tumor necrosis factor HLA class 1 factor receptor

[0621] ligand superfamily -0.99 Trefoil factor 2 -0.88 -0.99 histocompatibility -0.99 superfamily

[0622] member 10 antigen, alpha chain G member 13B

[0623] Interferon regulatory factor 2'-5'-oligoadenylate Monocyte differentiation Fibronectin -0.99 -0.87 -0.99 -0.99

[0624] 1 synthase 1 antigen CD14, soluble

[0625]

[0626] Example 6 - Scatter plot of selected proteins against bone readouts

[0627] Figure 5 A1-A5 and B1-B5 shows scatter plot of selected proteins against bone readouts. A: Trabecular Structural Model Index, B: Trabecular Thickness (Tb. Th [mm]), C: Trabecular BV / TV and DL Cortical BV / TV. Each dot represents an individual sample, colored by group. Groups correspond to Example 2, i.e. Group 1 High fibre diet in red (4.7% fiber), Group 2, no fiber diet in yellow, Group 3 in green (6HMOs + 2 bifidobacterial strains (B. infantis LGM11588 and B. lactis CNCM 1-3446); Group 4 in blue 6HMOs + 3 bifidobacterial strains (B. infantis LGM11588 and B. lactis CNCM 1-3446 and B. I. iuvenis CNCM I-5942), Group 5 in pink (2HMOs + 3 bifidobacterial strains (B. infantis LGM11588 and B. lactis CNCM 1-3446 and B. I. iuvenis CNCM I-5942)). The ellipses surrounding each group represent the 95% confidence intervals, indicating the spread and clustering of data points within each group. The scatter plots were produced with the R library ggplot2. Data from individual animals against individual values of bone readouts are plotted, as well as the group average (center of the ellipses), in order to observe the variability within the groups.

[0628] It was observed that for most of the top proteins-bone readout pairs, Group 2 is the one farthest from the other groups (having the lowest values for the majority of proteins, or the highest values for fibronectin and fibronectin fragment 4). On the opposite side of Group 2, it is Group 4 (or Group 3 in the case of Roundabout homolog 1) the group showing the higher or lower values. Using the bone readout values allows a partial separation of these groups, but including the proteins, it can be observed that there is an improved discrimination between the samples of each groups.

[0629] Example 7 - Bifidobacterium iuvenis synergistically produces beneficial metabolites when combined with a blend of 7 HMOs, including LNFP-I

[0630] This study was conducted with microbiota colonic incubations as described in Front Microbiol.

[0631] 2023 Apr 14;14:1131662.

[0632] 8 arms were used in the study. These consisted of:

[0633] 1. HMO blend

[0634] 2. HMO blend + B. infantis

[0635] 3. HMO blend + B. iuvenis

[0636] 4. HMO blend + B. infantis + B. iuvenis

[0637] 5. HMO blend + LNFP-I

[0638] 6. HMO blend + B. infantis + LNFP-I

[0639] 7. HMO blend + B. iuvenis + LNFP-I

[0640] 8. HMO blend + B. infantis + B. iuvenis + LNFP-I

[0641] 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 young individuals 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).

[0642] 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.

[0643] HMO Amount (g / L)

[0644] 2FL 2.46

[0645] 3FL 0.68

[0646] DFL 0.34

[0647] 3SL 0.31

[0648] 6SL 0.40

[0649] LNT 0.82

[0650] Total 5.00

[0651]

[0652] LNFP-I, when included, was dosed at a concentration 0.85 g / L in addition to the HMO blend.

[0653] 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.

[0654] Colonic incubations were carried out for 24 hours, with sampling at 0 and 24 hours for:

[0655] • SCFA levels by HPLC

[0656] 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.

[0657] 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 / -, B. infantis / 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.

[0658] 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.

[0659] Example 8 - Bifidobacterium iuvenis synergistically produces beneficial metabolites when combined with a blend of HMOs, including LNFP-I

[0660] 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.

[0661] Twenty-two arms were used in the study. These consisted of:

[0662] 1. Blank

[0663] 2. B. iuvenis

[0664] 3. LNFP-I

[0665] 4. HMO Blend I

[0666] 5. HMO Blend II

[0667] 6. HMO Blend I + LNFP-I

[0668] 7. HMO Blend II + LNFP-I 8. LNFP-I + B. iuvenis

[0669] 9. HMO Blend I + B. iuvenis

[0670] 10. HMO Blend II + B. iuvenis

[0671] 11. HMO Blend I + LNFP-I + 8. iuvenis

[0672] 12. HMO Blend II + LNFP-I + 8. iuvenis

[0673] 13. LNFP-I + 8. infantis

[0674] 14. HMO Blend I + 8. infantis

[0675] 15. HMO Blend II + B. infantis

[0676] 16. HMO Blend I + LNFP-I + B. infantis

[0677] 17. HMO Blend II + LNFP-I + 8. infantis

[0678] 18. LNFP-I + 8. iuvenis + B. infantis

[0679] 19. HMO Blend I + B. iuvenis + 8. infantis

[0680] 20. HMO Blend II + 8. iuvenis + B. infantis

[0681] 21. HMO Blend I + LNFP-I + B. iuvenis + 8. infantis

[0682] 22. HMO Blend II + LNFP-I + 8. iuvenis + B. infantis

[0683] The HMO blends used in the study were as follows:

[0684] HMO blend I: 2FL, 3FL, DFL, 3SL, 6SL, LNT

[0685] HMO Blend II: 2FL, 3FL, DFL, 3SL, 6SL, LNT, LNnT

[0686] Suitable amounts for the HMO blends are as follows:

[0687] 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

[0688] 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.

[0689] Suitably, B. infantis LMG11588 and 8. iuvenis CNCM I-5942 may be each dosed at a concentration of 5 x 107CFU / mL, whether individually, or in combination.

[0690] 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).

[0691] Colonic incubations were carried out for 48-hours, with sampling at 0, 24 and 48 hours for:

[0692] • SCFA analysis

[0693] • Metabolite analysis by LC-MS

[0694] 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 LIPLC 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).

[0695] Example 9 - Bifidobacterium iuvenis synergistically produces beneficial metabolites when combined with a blend of HMOs, including LNFP-I

[0696] As above in example 2, with the following modifications.

[0697] Design:

[0698] 1. Blank

[0699] 2. B. iuvenis

[0700] 3. B. infantis

[0701] 4. B. iuvenis + B. infantis

[0702] 5. LNFP-I

[0703] 6. HMO Blend I

[0704] 7. HMO Blend II

[0705] 8. HMO Blend I + LNFP-I

[0706] 9. HMO Blend II + LNFP-I

[0707] 10. LNFP-I + B. iuvenis

[0708] 11. HMO Blend I + B. iuvenis

[0709] 12. HMO Blend II + B. iuvenis 13. HMO Blend I + LNFP-I + B. iuvenis

[0710] 14. HMO Blend II + LNFP-I + B. iuvenis

[0711] 15. LNFP-I + 8. infantis

[0712] 16. HMO Blend I + 8. infantis

[0713] 17. HMO Blend II + 8. infantis

[0714] 18. HMO Blend I + LNFP-I + 8. infantis

[0715] 19. HMO Blend II + LNFP-I + 8. infantis

[0716] 20. LNFP-I + B. iuvenis + B. infantis

[0717] 21. HMO Blend I + B. iuvenis + 8. infantis

[0718] 22. HMO Blend II + 8. iuvenis + B. infantis

[0719] 23. HMO Blend I + LNFP-I + B. iuvenis + 8. infantis

[0720] 24. HMO Blend II + LNFP-I + 8. iuvenis + B. infantis

[0721] 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).

[0722] Doses:

[0723] 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.

[0724] HMO in HMO Blend I Amount (g / L)

[0725] 2FL 1.23

[0726] 3FL 0.34

[0727] DFL 0.17

[0728] 3SL 0.15

[0729] 6SL 0.20

[0730] LNT 0.41

[0731] Total 2.5 HMO HMO Blend II Amount (g / L)

[0732] 2FL 0.95

[0733] 3FL 0.37

[0734] DFL 0.11

[0735] 3SL 0.10

[0736] 6SL 0.17

[0737] LNT 0.33

[0738] LNnT 0.47

[0739] Total 2.5

[0740] 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.

[0741] 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.

[0742] Colonic incubations were carried out for 48-hours, with sampling at 0, 24 and 48 hours for:

[0743] • SOFA analysis (acetate and total SOFA)

[0744] • pH (acidification)

[0745] It can be seen that when B. iuvenis alone is used, this results in a larger final acetate increase over the control arm (Figure 7).

[0746] Additionally, in all cases, the HMO mix with additional LNFP-I result in larger final acetate (Figure 7) and final total SOFA 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.

[0747] Example 10

[0748] Naturally farrowed piglets from a commercial swine herd remained with the sows until postnatal day 2 (PND 2) before being transported to a specialized neonatal pig rearing system at the Piglet Nutrition and Cognition Laboratory (PNCL) on the University of Illinois campus. A total of 20 piglets were randomly assigned to treatment groups by equalizing initial body weight and genetics (i.e., litter of origin) across treatments, such that an equal number of pigs from each litter was assigned to each treatment group in every cohort. The treatment structure included a commercial milk replacer ad libitum without (CON n=10) or with (Bl n=10) 109CFU / d B-luvenis.

[0749] During the initial three days, piglets were administered either that Bifidobacterium longum subsp. iuvenis (Bl) or milk replacer (CON) through syringe feeding. Subsequently, unt / 7 28 days of age, that Bifidobacterium longum subsp. iuvenis was mixed with milk replacer and provided in individual bowls for the remainder of the nursing period.

[0750] On PND 29-56, pigs in the Bl group received a daily dose of that Bifidobacterium longum subsp. iuvenis at the beginning of the day (via syringe feeding). As the piglets will be group housed, the feeding procedure will ensure that all probiotic is consumed by each individual pig (i.e. using syringe). Probiotic treatment will not be given on the last day of the experiment (euthanasia day).

[0751] On PND 29-56, pigs were fed a nutritionally adequate solid diet manufactured at the University of Illinois Feed Technology Center starting on PND 28. The diets were manufactured in mash form (i.e., ground to small particle size) for pigs to consume ad libitum. Age-appropriate diets were formulated to maximize the concentrations of arabinan and arabinoxylan found in a natural ingredient matrix, which was accomplished using wheat-based products. These diets also contained dried whey of ovine origin, but no spray-dried porcine plasma, antibiotics, or antibiotic alternatives (e.g., no zinc oxide or copper sulfate), as necessary to support voluntary intake and growth in young pigs.

[0752] Bones were excised and evaluated as described below.

[0753] Ultrasound: Speed of sound (SOS) readings were measured using the Sunlight Omnisense® 9000S Bone Sonometer (BeamMed Ltd) as previously described (1, 2) in four different orientations (anterior, posterior, medial, lateral, Figure 8). The Sunlight Omnisense® is a portable ultrasonometer which emits and receives pulses of ultrasound along the femur bone at low 200-kHz frequency and measures the speed of sound in the femur (m / s). Ultrasound transmission gel (Aquasonic 100 Ultrasound Transmission Gel; Parker Laboratories Inc.) was used to obtain good acoustic contact between the probe surface and the soft tissue overlying the femur.

[0754] Micro-computed tomography

[0755] Micro-computed tomography (pCT UCT35, Scanco Medical AG, Basserdorf Switzerland) was used to assess trabecular and cortical microstructure respectively investigated at proximal metaphysis and midshaft diaphysis tibia as previously described (Bonnet et al JBMR 2017). Briefly, trabecular and cortical bone regions were evaluated using isotropic 18.5.m and 15 |_im voxels, respectively. For the tibial trabecular region, a bone slice of 4 mm was cut 2 mm below the bottom of the lowest condyle (Figure 9). This slice covers a region rich in trabeculae just below the growth plate, and is exempt of primary spongiosa. 150 slices were analysed in the middle of this 4 mm bone slice. Tibial cortical structure was assessed by cutting a 4 mm bone slice a tibial midshaft and analyzing 150 continuous CT slides located in the middle of this bone slice. Morphometric variables were computed from binarized images using direct, three-dimensional techniques that do not rely on prior assumptions about the underlying structure (3). For the trabecular bone regions, we assessed the bone volume fraction (BV / TV), Trabecular Thickness (Tb. Th,.m), Trabecular Number (Tb. N, mm-1) and trabecular connectivity density (Tb Conn Density, mm-3) as well as other parameters previously described (4, 5). For cortical bone at the tibial midshaft, we measured the Cortical Tissue Volume (Ct. TV, mm3), Bone Volume (Ct. BV, mm3), the Marrow Volume (BMaV, mm3) and the average Cortical Thickness (Ct. Th,.m). In addition, we evaluated cortical bone porosity (Ct. Po) in both metaphysis and diaphysis compartments.

[0756] Biomechanics (three point bending test)

[0757] Mechanical properties of the femur were assessed by three-point bending tests. Six hours before mechanical testing, the bones were thawed at room temperature. Each bone was secured on the two lower supports of the Universal Testing Machine (Zwick / Roell Z020; ZwickRoell GmbH & Co. KG, Ulm, Germany), with the anterior side facing up (Figure 10). The diameter of these supports was 2 mm, and the distance between the two supports was 4cm. The cross-head speed for all tests was 0.16 mm / s. Load-displacement curves were recorded using specialized software (testXpert III - v1.4). Biomechanical properties were calculated from these curves: ultimate force (the maximum force supported by the bone before fracture, Fmax, N); energy to ultimate force (work energy required to fracture the bone, Wmax, Nmm); and stiffness (extrinsic rigidity of the femur, S, N / mm). The anteroposterior diameter, the body weight, as well as the cohort of the pigs, were used for the normalization of the assays. To ensure good reproducibility between measurements, the femur was always mounted so that the cross-head could be applied just in the middle of the bone. Figure 11 shows the improvement in femur SOS in piglets receiving B. iuvenis alone at anterior, posterior and lateral orientation of the femur as well as higher femur SOS in piglets receiving B Iuvenis + 3’FL at posterior and lateral orientation compared to control.

[0758] The results are shown in Figure 11, where the variations are measured with respect to the median, represented by the horizontal line.

[0759] The results show that:

[0760] A +8.2% increase in anterior femur SOS was observed in the B iuvenis blend compared to the control group.

[0761] A +13.1% increase in posterior femur SOS was observed in the B iuvenis blend compared to the control group.

[0762] A +9.2% increase in posterior femur SOS was observed in the B iuvenis+3’FL blend compared to the control group.

[0763] A +12% increase in lateral femur SOS was observed in the B iuvenis blend compared to the control group.

[0764] A +19% increase in lateral femur SOS was observed in the B iuvenis+3’FL blend compared to the control group.

[0765] EMBODIMENTS

[0766] Various preferred features and embodiments of the present invention will now be described with reference to the following numbered paragraphs (paras).

[0767] 1. A composition for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual, wherein the composition comprises Bifidobacterium longum subsp. iuvenis.

[0768] 2. The composition according to para 1, wherein the Bifidobacterium longum subsp.

[0769] iuvenis has an Average Nucleotide Identity (ANI) of at least 98% with at least one Bifidobacterium longum strain selected from 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.

[0770] 3. The composition for use according to paras 1 or 2, wherein the composition further comprises at least one further probiotic and / or prebiotic.

[0771] 4. The composition for use according para 3, wherein the at least one further prebiotic comprises arabinan.

[0772] 5. The composition for use according to para 3, wherein the at least one further probiotic comprises Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis.

[0773] 6. The composition according to para 5, wherein:

[0774] (i) the Bifidobacterium longum subsp. infantis is Bifidobacterium longum subsp. infantis LMG 11588 or has an Average Nucleotide Identity (ANI) of at least 99.9% to Bifidobacterium longum subsp. infantis LMG 11588; and (ii) the Bifidobacterium animalis subsp. lactis is Bifidobacterium animalis subsp. lactis CNCM 1-3446 or has an Average Nucleotide Identity (ANI) of at least 99.9% ANI to Bifidobacterium animalis subsp. lactis CNCM 1-3446.

[0775] 7. The composition according to para 3, wherein the wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL and 3-FL.

[0776] 8. The composition according to para 3, wherein the wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL and 3SL. 9. The composition according to para 3, wherein the wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, and 3- FL.

[0777] 10. The composition according to para 3, wherein the wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, and LNnT.

[0778] 11. The composition according to para3, wherein the wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, 3-FL and LNnT.

[0779] 12. The composition for use according to para 3, 5 or 6, wherein the at least one further probiotic and / or prebiotic comprises 2-FL and 3-FL, optionally further comprising Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis. 13. The composition for use according to para 3 5, or 6, wherein the at least one further probiotic and / or prebiotic comprises 2-FL, 3-FL and Bifidobacterium longum subsp. infantis, optionally further comprising Bifidobacterium animalis subsp. lactis.

[0780] 14. The composition for use according to para 3, 5, or 6, wherein the at least one further probiotic and / or prebiotic comprises 2-FL, 3-F, Bifidobacterium longum subsp. infantis, and Bifidobacterium animalis subsp. lactis.

[0781] 15. The composition for use according to para 3, 5, or 6, wherein the at least one further probiotic and / or prebiotic consists of 2-FL, 3-FL and Bifidobacterium longum subsp. infantis.

[0782] 16. The composition for use according to para 3, 5, or 6, wherein the at least one further probiotic and / or prebiotic consists of 2-FL, 3-F, Bifidobacterium longum subsp. infantis, and Bifidobacterium animalis subsp. lactis.

[0783] 17. The composition for use according to any preceding paras, wherein the Bifidobacterium longum subsp. iuvenis'.

[0784] (i) is capable of metabolizing the HMO(s);

[0785] (ii) preferentially utilizes 3-FL over2’-FL; and / or

[0786] (iii) 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.

[0787] 18. The composition for use according to any preceding paras, wherein the composition is provided in the form of a nutritional composition, optionally wherein the composition is provided in the form of a growing-up milk.

[0788] 19. The composition for use according to any preceding paras, wherein the young individual suffered from and / or is suffering from stunted growth and / or faltering growth.

[0789] 20. The composition for use according to any preceding paras, wherein the composition improves one or more bone parameter selected from: bone mineral density (BMD), trabecular and cortical bone volume fraction (BV / TV), trabecular thickness (Tb. Th) 21. The composition for use according to any preceding paras, wherein the composition promotes catch-up growth, preferably wherein catch-up growth is determined using height velocity.

[0790] 22. The composition for use according to any preceding para, wherein the young individual is about 1 year of age or older, preferably wherein the young individual is from about 1 year to about 3 years of age. 23. The composition for use according to any preceding para, wherein the young individual is an infant.

[0791] 24. The composition for use according to any of paras 1 to 23, wherein the young individual is an animal, preferably wherein the animal is a pet.

[0792] 25. The composition for use according to any preceding para, wherein the young individual was born preterm or with low-birth weight or experienced intra-uterine growth retardation.

[0793] 26. The composition for use according to any preceding para, wherein the composition is administered by oral administration.

[0794] 27. The composition for use according to any preceding para, wherein the composition synergistically enhances bone growth and / or bone strength.

[0795] 28. The composition for use according to any preceding para, wherein the composition increases vitamin K2 production.

[0796] 29. The composition for use according to any preceding para, wherein the composition improves one or more bone parameter selected from: bone mineral density (BMD), trabecular bone volume fraction (BV / TV) and / or cortical bone volume (Ct. BV).

[0797] 30. The composition for use according to any preceding para, wherein the composition promotes catch-up growth, preferably wherein catch-up growth is determined using height velocity.

[0798] 31. Use of a composition comprising B. longum subsp. iuvenis in the manufacture of a medical food product for enhancing bone growth and / or bone strength in a young individual, wherein the composition comprises Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis and an 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).

[0799] 32. A method for enhancing bone growth and / or bone strength in a young individual, the method comprising administering to the young individual an effective amount of a composition comprising composition comprising B. longum subsp. iuvenis, Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis, and an 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).

[0800] 33. Use of a composition comprising B. longum subsp. iuvenis in the manufacture of a medical food product for enhancing bone growth and / or bone strength in a young individual, wherein the composition comprises Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis and an HMO mixture consisting of 2'- fucosyllactose (2FL) and 3-fucosyl lactose (3FL).

[0801] 34. A method for enhancing bone growth and / or bone strength in a young individual, the method comprising administering to the young individual an effective amount of a composition comprising composition comprising B. longum subsp. iuvenis, Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis and an HMO mixture consisting of 2'-fucosyllactose (2FL) and 3-fucosyl lactose (3FL).

[0802] Although the invention has been described by way of example, it should be appreciated that variations and modifications may be made without departing from the scope of the invention as defined in the claims. Furthermore, where known equivalents exist to specific features, such equivalents are incorporated as if specifically referred in this specification.

Claims

CLAIMS1. A composition for use in promoting bone growth, enhancing bone growth and / or bone strength in a young individual, wherein the composition comprises Bifidobacterium longum subsp. iuvenis.

2. The composition according to claim 1, 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.

3. The composition for use according to claim 1 or 2, wherein the composition further comprises at least one further probiotic and / or prebiotic.

4. The composition for use according claim 3, wherein the at least one further prebiotic comprises arabinan.

5. The composition for use according to claim 3, wherein the at least one further probiotic comprises Bifidobacterium longum subsp. infantis and / or Bifidobacterium animalis subsp. lactis.

6. The composition according to claim 5, wherein:(i) the Bifidobacterium longum subsp. infantis is Bifidobacterium longum subsp. infantis LMG 11588 or has an Average Nucleotide Identity (ANI) of at least 99.9% to Bifidobacterium longum subsp. infantis LMG 11588; and (ii) the Bifidobacterium animalis subsp. lactis is Bifidobacterium animalis subsp. lactis CNCM 1-3446 or has an Average Nucleotide Identity (ANI) of at least 99.9% ANI to Bifidobacterium animalis subsp. lactis CNCM 1-3446.

7. The composition according to claim 3, wherein the wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL and 3SL.

8. The composition according to claim 3, wherein the wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, and 3- FL.

9. The composition according to claim 3, wherein the wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, and LNnT.

10. The composition according to claim 3, wherein the wherein the at least one further prebiotic comprises an HMO mixture consisting of 2’-FL, DFL, LNT, 6SL, 3SL, 3-FL and LNnT.

11. The composition for use according to any preceding claim, wherein the Bifidobacterium longum subsp. iuvenis'.i. is capable of metabolizing one or more of the HMO(s), preferably all of the HMOs; ii. preferentially utilizes 3-FL over 2’-FL; and / oriii. 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.

12. The composition for use according to any preceding claim, wherein the composition is provided in the form of a nutritional composition, optionally wherein the composition is provided in the form of a growing-up milk.

13. The composition for use according to any preceding claim, wherein the young individual suffered from and / or is suffering from stunted growth and / or faltering growth.

14. The composition for use according to any preceding claim, wherein the composition improves one or more bone parameter selected from: bone mineral density (BMD), trabecular and cortical bone volume fraction (BV / TV) and / or trabecular thickness (Tb. Th).

15. The composition for use according to any preceding claim, wherein the composition promotes catch-up growth, preferably wherein catch-up growth is determined using height velocity.

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