Compositions and methods for reducing the incidence of diarrhea by increasing / enhancing Blautia obeum in the gut microbiota

Abstract

Methods and compositions for treating diarrhea, reducing the incidence of diarrhea, and / or preventing diarrhea in an infant or young child by increasing / enhancing Blautia obeum in the infant's or young child's gut microbiome. Suitably, the methods and compositions employ at least one arabinoxylan or arabinoxylan-containing material selected from the group consisting of: (i) whole kernel corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan.

Description

[Technical field]

[0001] The present disclosure relates to compositions and methods for treating diarrhea, reducing the incidence of diarrhea, and / or preventing diarrhea in infants or young children. [Background technology]

[0002] Diarrhea is a leading cause of childhood morbidity and mortality in the developing world and affects childhood health more generally. For example, diarrhea can increase a child's risk of death and disability by reducing the absorption of nutrients and fluids. Therefore, recognition and management of diarrhea is important, for example, to improve outcomes and increase the success of community-based programs.

[0003] The microbiome can refer to both the composition of microorganisms within an ecosystem and its "theatre of activity," which can include microbial structural elements (nucleic acids, proteins, lipids, polysaccharides), metabolic products (signaling molecules, toxins, organic molecules, inorganic molecules), and molecules produced by the coexisting host and structured by the surrounding environmental conditions (e.g., Berg, G., et al., 2020. Microbiome, 8(1), pp. 1-22). The gut microbiome changes rapidly and dramatically in the first few years of life (Dogra SK, et al. Microorganisms. 2021; 9(10): 2110). In infants or young children, certain factors such as mode of delivery, antibiotic use, and duration of exclusive breastfeeding affect the gut microbiome. Several other factors, such as the area of ​​residence, siblings, and furry pets, may also affect the gut microbiome of infants or young children (Stewart CJ, et al. Nature. 2018, Ho NT, et al. Nat. Commun. 2018). Importantly, the establishment of the gut microbiome of infants or young children has long-term effects on their health later in life (Dogra SK, et al. Gut Microbes. 2015;6(5):321-5).

[0004] WO 2015 / 066625 describes microbiome profiles associated with mature / healthy gut microbiota in a cohort of Bangladeshi infants.

[0005] Additional approaches and methods are needed to reduce the incidence and episodes of diarrhea in infants and young children.

[0006] [Summary of the Invention] The present disclosure is based, at least in part, on the surprising determination by the inventors that levels of Blautia obeum in the gut microbiome and putative identification of signaling molecules expressed by Blautia obeum are inversely correlated with diarrhea episodes in a cohort of infants and young children. Furthermore, the inventors have determined that diarrhea episodes occurring in the population were generally not the result of infection with Vibrio cholera or Clostridioides difficile. Without wishing to be bound by theory, the inventors believe that the compositions and methods provided by the present disclosure may reduce the incidence of diarrhea and / or prevent diarrhea in infants or young children by providing protection against pathogens and / or aiding in recovery from pathogens, such as enteric pathogens.

[0007] Thus, the present disclosure provides an approach for treating diarrhea, reducing the occurrence of diarrhea, and / or preventing diarrhea in infants or young children by increasing / enhancing Blautia obeum in the gut microbiota. The compositions and methods disclosed herein may increase / enhance the abundance and / or activity of Blautia obeum in the gut microbiota. In particular, the compositions and methods disclosed herein may increase the level of anti-pathogenic molecules produced by Blautia obeum in the gut microbiota. As an example, the anti-pathogenic molecules may reduce / inhibit the growth and / or activity of pathogenic microorganisms present in the gut microbiota.

[0008] Accordingly, a first aspect of the present disclosure provides a composition for treating diarrhea, reducing the incidence of diarrhea and / or preventing diarrhea in an infant or young child, the composition increasing / enhancing Blautia obeum in the gut microbiota of the infant or young child.

[0009] The present disclosure further provides a method for treating diarrhea, reducing the incidence of diarrhea, and / or preventing diarrhea in an infant or young child, comprising administering to an infant or young child in need thereof a composition that increases / enhances Blautia obeum in the gut microbiota.

[0010] The present disclosure further relates to the use of at least one arabinoxylan or arabinoxylan-containing material for treating diarrhea, reducing the incidence of diarrhea and / or preventing diarrhea in an infant or young child subject, wherein the at least one arabinoxylan or arabinoxylan-containing material increases / enhances Blautia obeum in the infant's or young child's gut microbiota (e.g., the at least one arabinoxylan or arabinoxylan-containing material is administered to the infant or young child in an amount effective to increase / enhance Blautia obeum in the infant's or young child's gut microbiota). The at least one arabinoxylan or arabinoxylan-containing material may be selected from the group consisting of: (i) whole kernel corn, (ii) corn arabinoxylan (e.g., isolated or purified corn arabinoxylan), (iii) corn bran (e.g., arabinoxylan-enriched corn bran), (iv) corn bran arabinoxylan (e.g., isolated or purified corn bran arabinoxylan), (v) whole wheat, (vi) wheat arabinoxylan (e.g., isolated or purified wheat arabinoxylan), (vii) wheat bran (e.g., arabinoxylan-enriched wheat bran), and (viii) wheat bran arabinoxylan (e.g., isolated or purified wheat bran arabinoxylan).

[0011] The present disclosure further provides a method for the preparation of an arabinoxylan or arabinoxylan-containing material, preferably selected from the group consisting of: (i) whole kernel corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole kernel wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan, for use in an infant. or for use in the manufacture of a medicament for reducing the incidence of and / or preventing diarrhea in an infant, wherein the at least one arabinoxylan or arabinoxylan-containing material increases / enhances Blautia obeum in the infant's or infant's gut microbiota (e.g. a medicament comprising at least one arabinoxylan or arabinoxylan-containing material is administered to an infant or infant in an amount effective to increase / enhance Blautia obeum in the infant's or infant's gut microbiota).

[0012] Preferably, the arabinoxylan or arabinoxylan-containing material is selected from whole wheat, wheat arabinoxylan, wheat bran, and wheat bran arabinoxylan. Most preferably, the arabinoxylan or arabinoxylan-containing material is wheat arabinoxylan or wheat bran arabinoxylan.

[0013] The disclosure further relates to use of a dark chocolate (e.g., comprising at least 85% cocoa content) for treating diarrhea, reducing the incidence of diarrhea and / or preventing diarrhea in an infant or young child subject, wherein the dark chocolate increases / enhances Blautia obeum in the infant or young child's gut microbiome.The disclosure further relates to a dark chocolate (e.g., comprising at least 85% cocoa content) for use in treating diarrhea, reducing the incidence of diarrhea and / or preventing diarrhea in an infant or young child subject, wherein the dark chocolate increases / enhances Blautia obeum in the infant or young child's gut microbiome.

[0014] The disclosure further relates to the use of dark chocolate (e.g., comprising at least 85% cocoa content) in the manufacture of a medicament for treating diarrhea, reducing the incidence of diarrhea, and / or preventing diarrhea in an infant or young child subject, wherein the dark chocolate increases / enhances Blautia obeum in the infant or young child's gut microbiome.

[0015] Preferably, the diarrhea is not caused by Vibrio cholerae infection.

[0016] Suitably the infant or toddler is less than about 60 months of age, suitably less than 36 months of age, suitably between about 4 and about 36 months of age or between about 10 and about 36 months of age.

[0017] Suitably the composition is a dietary or nutritional composition.

[0018] For example, the dietary composition / dietary or nutritional composition / nutritional intervention may be a food, a beverage, a powdered supplement, an infant or toddler formula, an infant or toddler composition intended to be added to or diluted in breast milk, such as a breast milk fortifier, or a food, such as a food supplement, intended to be taken alone or in combination with breast milk as an infant or toddler composition.

[0019] Suitably, the dietary or nutritional composition / intervention comprises at least one arabinoxylan or arabinoxylan-containing material, preferably selected from the group consisting of: (i) whole kernel corn, (ii) corn arabinoxylan (e.g., isolated or purified corn arabinoxylan), (iii) corn bran (e.g., arabinoxylan-rich corn bran), (iv) corn bran arabinoxylan (e.g., isolated or purified corn bran arabinoxylan), (v) whole kernel wheat, (vi) wheat arabinoxylan (e.g., isolated or purified wheat arabinoxylan), (vii) wheat bran (e.g., arabinoxylan-rich wheat bran), and (viii) wheat bran arabinoxylan (e.g., isolated or purified wheat bran arabinoxylan).

[0020] Suitably, the dietary or nutritional composition / intervention comprises dark chocolate (e.g. comprising at least 85% cocoa content).

[0021] The disclosure further provides a composition comprising Blautia obeum for treating diarrhea, reducing the incidence of diarrhea, and / or preventing diarrhea in an infant or young child, wherein the diarrhea is not caused by Vibrio cholerae infection.

[0022] The disclosure further provides a method for predicting whether an infant or young child is at risk for diarrhea, the method comprising measuring a level of Blautia obeum in one or more samples obtained from the infant or young child. [Brief description of the drawings]

[0023] [Figure 1] FIG. 1 is a schematic diagram of the microbiome and health study. [Diagram 2]Distribution of diarrhea episodes in the microbiota and health study. Healthy vs. unhealthy diarrhea outcomes are defined by cumulative diarrhea prevalence score from 0 to 24 months of age. Healthy infants were defined as having zero diarrhea episodes by 24 months of age, and unhealthy infants were defined as having three or more diarrhea episodes by 24 months of age. [Figure 3A] Differences (cumulative scores) of Blautia obeum in the gut microbiome of children with 0 (healthy) vs. 3 or more (unhealthy) diarrhea episodes from 0 to 24 months of age. (A) Mean profiles with 95% confidence intervals. (B) Bar plot with confidence intervals at the most discriminatory time point (18 months). [Figure 3B] Differences (cumulative scores) of Blautia obeum in the gut microbiome of children with 0 (healthy) vs. 3 or more (unhealthy) diarrhea episodes from 0 to 24 months of age. (A) Mean profiles with 95% confidence intervals. (B) Bar plot with confidence intervals at the most discriminatory time point (18 months). [Figure 4A] Differences (cumulative scores) comparing Blautia obeum in the gut microbiome of children with 0 (healthy) and 3 or more (unhealthy) diarrhea outcomes at 10-24 months of age. (A) Lowess fit, permutation n=100. (B) Binomial fit, permutation n=1000. Time intervals with statistically significant differences as determined by permutation tests are shaded grey (Metwally AA,et al.Microbiome.2018). [Figure 4B] Differences (cumulative scores) comparing Blautia obeum in the gut microbiome of children with 0 (healthy) and 3 or more (unhealthy) diarrhea outcomes at 10-24 months of age. (A) Lowess fit, permutation n=100. (B) Binomial fit, permutation n=1000. Time intervals with statistically significant differences as determined by permutation tests are shaded grey (Metwally AA,et al.Microbiome.2018). [Diagram 5] Example of a random forest cross-sectional model to determine whether levels of Blautia obeum predict risk of diarrhea. [Figure 6] 1 is a preferred structure of wheat arabinoxylan for use in the compositions and methods disclosed herein. [Figure 7] The effect of specific fibers on pH in 12-month-old infants (n=6) is shown compared to a no substrate control (NSC) and a reference prebiotic (IN). Samples were taken 24 hours after simulated colonic incubation. Statistically significant differences compared to NSC are visualized by * (0.1<adj. p-value<0.2), ** (0.05<adj. p-value<0.1) or *** (adj. p-value<0.05), whereas differences compared to IN are indicated by $ / $$ / $$$. [Figure 8] The effect of specific fibers on total SCFA (short chain fatty acids) in 12-month-old infants (n=6) is shown compared to a no substrate control (NSC) and a reference prebiotic (IN). Samples were taken 24 hours after simulated colonic incubation. Statistically significant differences compared to NSC are visualized by * (0.1<adj. p-value<0.2), ** (0.05<adj. p-value<0.1) or *** (adj. p-value<0.05), whereas differences compared to IN are indicated by $ / $$ / $$$. [Figure 9] The effect of specific fibers on acetate in 12-month-old infants (n=6) is shown compared to a no substrate control (NSC) and a reference prebiotic (IN). Samples were collected 24 hours after simulated colonic incubation. Statistically significant differences compared to NSC are visualized by * (0.1<adj. p-value<0.2), ** (0.05<adj. p-value<0.1) or *** (adj. p-value<0.05), whereas differences compared to IN are indicated by $ / $$ / $$$. [Figure 10]The effect of specific fibers on propionic acid in 12-month-old infants (n=6) is shown compared to a no substrate control (NSC) and a reference prebiotic (IN). Samples were taken 24 hours after simulated colonic incubation. Statistically significant differences compared to NSC are visualized by * (0.1<adj. p-value<0.2), ** (0.05<adj. p-value<0.1) or *** (adj. p-value<0.05), whereas differences compared to IN are indicated by $ / $$ / $$$. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] Various preferred features and embodiments of the present disclosure will now be described by way of non-limiting examples, it being understood that a person skilled in the art may combine all features of the present disclosure disclosed herein without departing from the scope of the disclosed disclosure.

[0025] It should be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0026] As used herein, the terms "comprising," "comprises," and "comprised of" are synonymous with "including," "includes," or "containing," "contains," are inclusive or open-ended, and do not exclude additional, unspecified members, elements, or method steps. The terms "comprising," "comprises," and "comprised of" also include the term "consisting of."

[0027] Numeric ranges are inclusive of the numbers defining the range.

[0028] The terms "at least one of" and "and / or" used in the context of "at least one of X or Y" and "X and / or Y", respectively, should be interpreted as "X", or "Y", or "X and Y". For example, "at least one arabinoxylan or arabinoxylan-containing substance" and "arabinoxylan and / or arabinoxylan-containing substance" should be interpreted as "arabinoxylan", "arabinoxylan-containing substance", or "both arabinoxylan and arabinoxylan-containing substance".

[0029] "Prevention" includes reducing the risk, incidence and / or severity of a condition or disorder. The terms "treatment" and "treating" include both prophylactic or preventative treatment (treatment that prevents and / or delays the onset of a pathological condition or disorder of interest) and curative, therapeutic or disease-modifying treatment, including, for example, therapeutic measures to cure, delay, reduce symptoms and / or halt the progression of a diagnosed pathological condition or disorder, as well as treatment of patients at risk of or suspected of having a disease, and patients who are unwell or diagnosed with a disease or medical condition. The terms "treatment" and "treating" do not necessarily mean that the subject is treated until fully cured. The terms "treatment" and "treating" also refer to maintaining and / or improving the health of individuals who are not suffering from a disease but who may be susceptible to an unhealthy condition. The terms "treatment" and "treating" are also intended to include the synergism or otherwise potentiation of one or more primary preventative or therapeutic measures. By way of non-limiting example, treatment can be performed by the patient, a caregiver, a doctor, a nurse, or another medical professional.

[0030] As used herein, a prophylactically or therapeutically "effective amount" is an amount that prevents a deficiency, treats a disease or medical condition in an individual, or, more generally, reduces symptoms, manages disease progression, or provides a nutritional, physiological, or medical benefit to an individual. The relative terms "improved," "increased," "increased / enhanced," "promoted," and the like refer to the effect on Blautia obeum in the gut microbiome of an infant or young child by administration of a composition comprising at least one arabinoxylan or arabinoxylan-containing material, preferably a material selected from the group consisting of (i) whole corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan.

[0031] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Any publications cited herein should not be construed as an admission that they constitute prior art to the claims appended hereto.

[0032] The methods and systems disclosed herein may be used by physicians, medical professionals, laboratory technicians, infant or child care providers, and the like.

[0033] composition The composition may be suitable or suitable for administration to an infant or toddler in any suitable form, such as a nutritional composition in a dosage unit (e.g., tablet, capsule, powder sachet, etc.). The composition may be in the form of a powder, semi-liquid or liquid. The composition may be added to a nutritional composition, an infant formula, a food composition, a supplement for an infant or toddler, a baby food, a follow-up formula, growing-up milk, an infant or toddler cereal, or a fortifier. In some embodiments, the composition of the present disclosure is a supplement or fortifier that may be intended for an infant formula, a baby food, an infant or toddler cereal, growing-up milk, an infant or toddler.

[0034] The terms "complementary feeding period", "complementary period", "transitional period", "transitional feeding period" and "weaning period" may be used interchangeably and refer to the period during which milk, either breast milk or formula, is replaced with other foods in the diet of an infant or toddler. An infant or toddler is typically gradually changed or transitioned from an exclusive milk-feeding diet, either breast-fed or formula-fed, to a mixed diet that includes milk and / or solid foods. The transition period varies from infant to toddler, but typically includes between about 4 months and about 18 months of age, e.g., between about 6 months and about 18 months of age, although in some cases it may extend up to about 24 months of age or longer. In humans, the weaning period typically begins between 4-6 months of age and is considered complete when the infant or toddler is no longer receiving breast milk or infant formula, typically at about 24 months of age, hi some embodiments, the weaning period is between 4 and 24 months of age.

[0035] Suitably the composition is a dietary or nutritional composition.

[0036] The expression "dietary composition" or "nutritional composition" refers to any type of composition or formula that provides nutritional benefits to an individual and can be safely consumed by humans or animals. Such nutritional compositions can be in solid (e.g., powder), semi-solid or liquid form and can include one or more macronutrients, micronutrients, food additives, water, etc. For example, nutritional compositions can include the following macronutrients: a protein source, a lipid source, a carbohydrate source, and any combination thereof. Furthermore, nutritional compositions can include the following micronutrients: vitamins, minerals, fiber, phytochemicals, antioxidants, prebiotics, probiotics, and any combination thereof. The composition can also include food additives such as stabilizers (if provided in solid form) or emulsifiers (if provided in liquid form). The amount of each ingredient can be expressed in g / 100g of the composition on a dry weight basis in the case of solids, e.g. powders, and in g / L concentration of the composition in the case of liquids (the latter also includes liquid compositions obtained after reconstitution of powders with liquids such as milk, water, etc., e.g. reconstituted infant or toddler formulas or follow-on / follow-up formulas, or infant or toddler cereal products, or other formulas designed for infant, toddler or toddler nutrition). In general, the nutritional composition can be formulated for enteral, oral, parenteral or intravenous intake, and typically comprises one or more nutrients selected from lipids or fat sources, protein sources and carbohydrate sources. Preferably, the nutritional composition is for oral administration.

[0037] In a particular embodiment, the composition of the present disclosure is a "synthetic nutrient composition." The expression "synthetic nutrient composition" refers to a mixture obtained by chemical and / or biological means.

[0038] As used herein, the expression "infant formula" refers to a food intended for the specific nutritional supplementation of infants during the first month of life, which meets the nutritional requirements of infants falling within this category (Article 2(c) of the European Commission Directive 91 / 321 / EEC 2006 / 141 / EC of 22 December 2006 for infant and follow-on formulas) by the milk itself. The formula is intended for infants or young children and also refers to nutritional compositions as defined in Codex Alimentarius (Codex STAN72-1981) and special infant foods (including foods for specific medical purposes). The expression "infant formula" encompasses both "infant starter formulas" and "follow-up formulas" or "follow-on formulas".

[0039] "Follow-up formulas" or "follow-on formulas" are usually given from 6 months onwards and constitute the main liquid component of the increasingly diversified diet of infants in this category.

[0040] The expression "infant food" means a food intended for a specific nutritional use by an infant or young child during the first year of life.

[0041] The expression "infant or toddler cereal composition" means a food product intended for a specific nutritional use by an infant or toddler during the first year of life.

[0042] The expression "growing-up milk" (or GUM) refers to a milk drink, generally with added vitamins and minerals, targeted at young children or infants.

[0043] A "fortifier" may be a liquid or solid nutritional composition suitable for fortifying or mixing with human milk, infant or toddler formula, or growing-up milk. Thus, the fortifier may be administered after dissolution in human breast milk, after dissolution in infant or toddler formula, after dissolution in growing-up milk, or after dissolution in human breast milk fortified with other nutrients, or may be administered as a stand-alone composition. When administered as a stand-alone composition, the milk fortifier may also be identified as a "supplement."

[0044] Suitably the composition may include a prebiotic.

[0045] The term "prebiotic" refers to non-digestible carbohydrates that benefit the host by selectively stimulating the growth and / or activity of healthy bacteria in the human colon (Gibson GR, et al. Nat Rev Gastroenterol Hepatol. 2017).

[0046] Suitably the prebiotic is provided in the form of dietary fibre, for example the dietary fibre may be prebiotic fibre.

[0047] Suitably, the prebiotics may be included in ingredients, such as dietary ingredients.

[0048] Such ingredients may be selected from the group consisting of purified polysaccharides or oligosaccharides, dietary fibre ingredients, semi-refined food ingredients, raw food ingredients, food additives, human milk oligosaccharides (HMOs), semi-refined or purified peptidoglycans.

[0049] The semi-refined food ingredients may be extracts of fruits, vegetables or cereals.

[0050] The raw food ingredient may be a fruit, vegetable or grain.

[0051] The food additive may be guar gum or gum arabic.

[0052] Suitably, the prebiotic composition comprises a prebiotic (e.g. contained in ingredients or fibre) that increases / boosts Blautia obeum in the gut microbiota.

[0053] For example, the composition may comprise at least one arabinoxylan or arabinoxylan-containing material, preferably selected from the group consisting of: (i) whole corn, (ii) corn arabinoxylan (e.g., isolated or purified corn arabinoxylan), (iii) corn bran (e.g., arabinoxylan-rich corn bran), (iv) corn bran arabinoxylan (e.g., isolated or purified corn bran arabinoxylan), (v) whole wheat, (vi) wheat arabinoxylan (e.g., isolated or purified wheat arabinoxylan), (vii) wheat bran (e.g., arabinoxylan-rich wheat bran), and (viii) wheat bran arabinoxylan (e.g., isolated or purified wheat bran arabinoxylan).

[0054] Arabinoxylans are non-starch polysaccharides present in the cell walls of plant tissues and are the major non-starch polysaccharides in cereals and grasses.

[0055] Arabinoxylan may refer to a polysaccharide comprising arabinose and xylose. Arabinoxylan may refer to a polysaccharide comprising a linear backbone of xylan with arabinose side chain residues. Arabinoxylan may refer to a polysaccharide comprising a linear backbone of xylan with complex side chains comprising arabinose. Arabinoxylan may refer to a polysaccharide comprising a linear β-(1-4) linked xylan backbone with α-1-arabinofuranose side chain residues linked via α-(1-3) and / or α-(1-2) linkages. Arabinoxylan may include side chains with additional sugars such as xylose, galactose and / or glucuronic acid. Arabinoxylan may include highly branched and / or complex and / or simply branched side chains.

[0056] Suitably the arabinoxylan may be wheat, maize or barley arabinoxylan.

[0057] As an example, maize and maize bran arabinoxylans have been shown to have beneficial effects on the growth and / or survival of Blautia or Blautia obeum (see Vatanen et al.; Cell; 2016; 165(4); 842-853 and Nguyenet al; Microbiome; 2020 18:118). Maize bran arabinoxylans typically contain a backbone of xylose and arabinose, in particular linear xylose with arabinose forming branch points. Arabinoxylans may further contain galactose. Arabinoxylans may be extracts, such as maize, maize bran, wheat, or alkaline extracts from wheat bran. An example of maize bran arabinoxylan fiber is BIO-FIBER GUM (Agrifiber Holdings LLC, Illinois, USA). An example of wheat bran arabinoxylan is shown in FIG. 6.

[0058] As mentioned above, some embodiments use corn bran and / or wheat bran that can be sifted out and / or sieved out from other parts of corn or wheat, and corn bran and wheat bran can still provide the benefits disclosed herein because they are enriched in arabinoxylan. In particular, refined grains do not contain arabinoxylan (or at least do not contain a sufficient amount of arabinoxylan to achieve the benefits disclosed herein). In some embodiments, corn arabinoxylan, corn bran arabinoxylan, wheat arabinoxylan or wheat bran arabinoxylan can be in a refined / extracted form, for example, available as a commercial product from a commercial supplier.

[0059] Preferably, the arabinoxylan or arabinoxylan-containing material is selected from whole wheat, wheat arabinoxylan, wheat bran, and wheat bran arabinoxylan. Most preferably, the arabinoxylan or arabinoxylan-containing material is wheat arabinoxylan or wheat bran arabinoxylan.

[0060] In addition to or instead of at least one arabinoxylan or arabinoxylan-containing material, the composition may include dark chocolate (e.g., containing at least 85% cocoa content). By way of example, dark chocolate (e.g., containing at least about 85% cocoa content) has been shown to have a beneficial effect on the growth and / or survival of Blautia obeum (see Shin JH, et al.; J Nutr Biochem; 2022). The dark chocolate may be any suitable dark chocolate product (e.g., containing at least about 85% cocoa content). The cocoa may be in the form of cocoa powder. The dark chocolate may include fat, protein, sugar and polyphenols.

[0061] The nutritional composition may comprise oligosaccharides (e.g. human milk oligosaccharides) and / or at least one type of fiber and / or at least one type of precursor thereof. The oligosaccharides and / or fibers and / or their precursors may be selected from the list comprising galactooligosaccharides (GOS), fructooligosaccharides (FOS), inulin, xylooligosaccharides (XOS), polydextrose, and any combination thereof. These ingredients may typically be in an amount of 0-10% by weight of the composition. In a particular embodiment, the nutritional composition may also contain at least one BMO (milk oligosaccharide).

[0062] The nutritional composition may include a protein source. The protein may be in an amount of 1.6-3 g / 100 kcal.

[0063] In addition to soy-based protein sources, protein sources based on whey, casein and mixtures thereof may also be used. With regard to whey protein, the protein source may be based on acid whey or sweet whey or mixtures thereof and may contain α-lactalbumin and β-lactoglobulin in any desired ratio.

[0064] In some embodiments, the protein source is predominantly whey (i.e., more than 50% of the protein, e.g., 60% or 70% is derived from whey protein). The protein may be in an intact state, in a hydrolyzed state, or a mixture of proteins in an intact state and in a hydrolyzed state. The term "intact" means that the majority of the protein is in an intact state, i.e., the molecular structure is not altered, e.g., at least 80% of the protein is intact, e.g., at least 85% of the protein is intact, preferably at least 90% of the protein is intact, even more preferably at least 95% of the protein is intact, e.g., at least 98% of the protein is intact. In a particular embodiment, the protein is completely intact.

[0065] In a particular embodiment, the proteins of the nutritional composition are hydrolyzed, fully hydrolyzed or partially hydrolyzed. The degree of hydrolysis (DH) of the proteins may be between 8 and 40, or between 20 and 60, or between 20 and 80, or greater than 10, 20, 40, 60, 80 or 90. Alternatively, the protein component may be replaced by a mixture or synthetic amino acids, for example for premature or low birth weight infants.

[0066] The term "hydrolyzed" in the context of this disclosure means that the protein has been hydrolyzed or broken down into its component amino acids. The protein may be either fully hydrolyzed or partially hydrolyzed. For example, it may be desirable to provide partially hydrolyzed protein (degree of hydrolysis 2-20%) to infants or young children who are considered to be at risk of developing cow's milk allergy. If hydrolyzed protein is required, the hydrolysis process may be carried out as desired and as known in the art. For example, whey protein hydrolysates may be prepared by enzymatic hydrolysis of a whey fraction in one or more steps. It has been found that if the whey fraction used as the starting raw material is substantially lactose-free, the protein undergoes significantly less lysine blackage during the hydrolysis process. This allows the degree of lysine blackage to be reduced from about 15% total lysine by weight to less than about 10% lysine by weight, e.g., about 7% lysine by weight, significantly improving the nutritional value of the protein source.

[0067] In one embodiment of the disclosure, at least 70% of the protein is hydrolyzed, such as at least 80% of the protein is hydrolyzed, such as at least 85% of the protein is hydrolyzed, or at least 90%, 95%, 98% of the protein is hydrolyzed, in certain embodiments, 100% of the protein is hydrolyzed.

[0068] The nutritional composition can include a carbohydrate source.This is particularly preferred when the nutritional composition is an infant formula.In this case, any carbohydrate source such as lactose, sucrose, saccharose, maltodextrin, starch and their mixtures that are conventionally found in infant formulas may be used, but one of the preferred carbohydrate sources is lactose.

[0069] The nutritional composition may contain a lipid source. This is particularly appropriate when the nutritional composition is an infant formula. In this case, the lipid source may be any lipid or fat suitable for use in infant formula. 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 acid and a-linolenic acid may also be added, as well as small amounts of oils, such as fish oils or microbial oils that are rich in preformed arachidonic acid and docosahexaenoic acid. The ratio of n-6 fatty acids to n-3 fatty acids in the fat source may be about 5:1 to about 15:1, for example, about 8:1 to about 10:1.

[0070] The nutritional composition may also contain nutritionally significant amounts of vitamins and minerals that are considered essential for the daily diet. Minimum requirements have been established for certain vitamins and minerals. Examples of minerals, vitamins, and other nutrients that may be optionally present in the compositions of the present disclosure 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, phosphorus, 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 amount of certain minerals and other vitamins vary depending on the target population. If necessary, the nutritional composition of the present disclosure may contain emulsifiers and stabilizers, such as soybean, lecithin, citrate esters of mono- and diglycerides, and the like.

[0071] The nutritional composition may also optionally contain other substances that may have beneficial effects, such as lactoferrin, nucleotides and nucleosides.

[0072] The nutritional compositions may be prepared in any suitable manner. The compositions will now be described by way of example.

[0073] For example, a formula, such as an infant formula, may be prepared by blending together a protein source, a carbohydrate source, and a fat source in appropriate proportions. At least one arabinoxylan or arabinoxylan-containing material as described herein may be added. If used, an emulsifier may be included at this point. Vitamins and minerals may be added at this point, but are typically added later to avoid thermal degradation. Any lipophilic vitamins and emulsifiers, etc., may be dissolved in the fat source prior to blending. Water, preferably water that has been treated with reverse osmosis, may then be mixed to form a liquid mixture. The temperature of the water may range from about 50°C to about 80°C, as appropriate, to aid in the dispersion of the ingredients. A commercially available liquefying device may be used to form the liquid mixture.

[0074] The liquid mixture may then be homogenized.

[0075] The liquid mixture can then be subjected to a heat treatment to reduce the bacterial load, for example, by rapidly heating the liquid mixture for about 5 seconds to about 5 minutes to a temperature in the range of about 80° C. to about 150° C. This heating can be performed by steam injection, by autoclave, or by a heat exchanger, for example a plate heat exchanger.

[0076] The liquid mixture may then be cooled, for example by flash cooling, to about 60°C to about 85°C. The liquid mixture may then be homogenized again, for example in two stages, at about 10 MPa to about 30 MPa in the first stage and about 2 MPa to about 10 MPa in the second stage. The homogenized mixture may then be further cooled and any heat-sensitive ingredients, such as vitamins and minerals, may be added. The pH and solids content of the homogenized mixture are typically adjusted at this point.

[0077] If the final product is a powder, the homogenized mixture is transferred to a suitable drying device, such as a spray dryer or freeze dryer, and converted to a powder. The powder should have a moisture content of less than about 5% by weight. The mixture may be spray dried or freeze dried.

[0078] If a liquid composition is preferred, the homogenized mixture may be sterilized and then aseptically filled into suitable containers, or may be filled into the containers first and then retorted.

[0079] The nutritional composition can be given, for example, immediately after the birth of the infant. The nutritional composition of the present disclosure can also be given to the infant during the first week of life, or during the first two weeks of life, or during the first three weeks of life, or during the first month of life, or during the first two months of life, or during the first three months of life, or during the first four months of life, or during the first six months of life, or during the first eight months of life, or during the first ten months of life, or during the first year of life, or during the first two years of life or more. In some particularly advantageous embodiments of the present disclosure, the composition is given (or administered) to the infant or toddler from about 6 months of age of the infant or toddler. For example, the composition can be administered from about 6 months, about 10 months, about 12 months, about 14 months, about 16 months, about 20 months, about 24 months, or about 36 months of age.

[0080] Suitably the composition is given (or administered) to the infant or young child from about 10 months of the infant's or young child's birth.

[0081] Suitably, the composition may be administered to an infant or toddler between about 6 and about 60 months of age, between about 6 and about 48 months of age, or between about 6 and about 36 months of age. Suitably, the composition may be administered to an infant or toddler between about 10 and about 60 months of age, between about 10 and about 48 months of age, or between about 10 and about 36 months of age.

[0082] In some embodiments, the nutritional composition is given to the infant or toddler as a composition that complements breast milk. In some embodiments, the infant or toddler receives breast milk for at least the first two weeks, the first one, two, four, or six months. In some embodiments, the nutritional composition of the present disclosure is given to the infant or toddler after such periods of breast-feeding or is given together with such periods of breast-feeding. In another embodiment, the nutritional composition is given to the infant or toddler alone or as the primary nutritional composition for at least one period, such as after one, two, or four months of age, for at least one, two, four, or six months of age.

[0083] Suitably the composition may include a probiotic including Blautia obeum.

[0084] The term "probiotics" refers to microbial cell preparations or microbial cell components that have beneficial effects 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; Hill C, et al. Nat Rev Gastroenterol Hepatol. 2014). Microbial cells are broadly bacteria or yeasts.

[0085] Blautia obeum may be present in the composition, for example, in an amount of about 10 per gram of the composition on a dry weight basis. 3 ~10 12 cfu of probiotic strain, preferably 10 7 ~10 12 cfu, e.g. 10 8 ~10 10 In some embodiments, the Blautia obeum is live. In some other embodiments, both live and inactivated Blautia obeum may be present.

[0086] The term "cfu" should be understood as colony forming unit.

[0087] Suitably, the present disclosure may include the use of a combination of a nutritional or dietary composition as described herein with a probiotic composition as described herein, for example a probiotic composition comprising Blautia obeum. Suitably, the compositions and methods disclosed herein may include the use of a synbiotic. As used herein, a synbiotic may refer to a mixture comprising a microorganism and a substrate(s) selectively utilized by the microorganism, preferably the combination provides a health benefit to the host (see, for example, Swanson KS, et al. Nat Rev Gastroenterol Hepatol. 2020). For example, the symbiont of the present invention may include arabinoxylan, preferably wheat or corn arabinoxylan, as a prebiotic, and / or dark chocolate (e.g., at least 85% cocoa content), and Blautia obeum as a probiotic.

[0088] The compositions according to the present disclosure may be administered in any suitable manner. Preferably, the compositions are for oral administration. Thus, it is preferred that the compositions are administered orally.

[0089] In some embodiments, the compositions according to the present disclosure may be for use before and / or during the weaning period. The nutritional compositions may be administered (or given or fed) at any age and for any period as needed.

[0090] diarrhea Diarrhea may be defined as 3 or more stools per day in a form that is looser than normal (e.g., loose stools and / or watery). If this lasts for less than 14 days, it may be diagnosed as acute diarrhea. Persistent diarrhea may be diagnosed as 3 or more stools per day in a form that is looser than normal and lasts for more than 14 days but less than one month. Chronic diarrhea may be diagnosed as 3 or more stools per day in a form that is looser than normal and lasts for more than one month.

[0091] Acute, persistent, and chronic diarrhea may have associated symptoms including abdominal cramps or pain, fever, nausea, vomiting, fatigue, urgency, weight loss, and / or malnutrition. Acute, persistent, and chronic diarrhea are symptoms in themselves. Causes of acute diarrhea are well known in the art, and non-limiting examples include food allergies, antibiotic use, enteric pathogen infection, and radiation therapy. Causes of persistent diarrhea are well known in the art, and non-limiting examples include food allergies, antibiotic use, enteric pathogen infection, colectomy, colon cancer, ulcerative colitis, necrotizing enterocolitis, Crohn's disease, and radiation therapy. Causes of chronic diarrhea are well known in the art, and non-limiting examples include food allergies, pharmacological agent use, enteric pathogen infection, colectomy, colon cancer, ulcerative colitis, necrotizing enterocolitis, Crohn's disease, and radiation therapy. Pharmaceutical agents known to cause diarrhea are well known in the art and may include, but are not limited to, antibiotics, anti-TNF agents, chemotherapeutic agents, antacids, proton pump inhibitors (e.g., omeprazole, esoprazole, lansoprazole, rabeprazole, pantoprazole, cimetidine, ranitidine, nidiatidine), drugs that suppress the immune system (e.g., mycophenolate), antidepressants, blood pressure medications, digitalis, diuretics, cholesterol lowering agents, lithium, theophylline, thyroid hormones, and colchicine.

[0092] Suitably, the diarrhea referred to herein may be caused by an enteric pathogen infection.

[0093] Without wishing to be bound by theory, the inventors believe that the compositions and methods of the present disclosure may reduce the incidence of and / or prevent diarrhea in infants or young children by providing defense against and / or aiding in recovery from pathogens, such as enteric pathogens.

[0094] Enteric pathogens include Campylobacter jejuni, Campylobacter coli, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Salmonella enterica, Shigella flexneri, Shigella sonnei, Shigella dysenteriae, Campylobacter upsaliensis, Yersinia enterocolitica, and Yersinia pseudotuberculosis. pseudotuberculosis, Vibrio cholerae, Vibrio parahaemolyticus, Clostridium difficile, Entamoeba histolytica, Entamoeba dispar, Endolimax nana, Lodamoeba butschii, Chilomastix mesnili, Blastocystis hominis, Trichomonas hominis, Giardia intestinalis, Giardia lamblia, Cryptosporidium parvum parvum, Isospora belli, Dientamoeba fragilis, Microsporidia, Strongyloides stercoralis, Angiostrongyluscostaricensis, Schistosoma mansoni, Schistosoma japonicum, Cyclospora cayetanensis, Enterocytozoon bieneusi, Enterocytozoon helium, Encephalitozoon intestinalis, Encephalitozoon cuniculi, Ascaris lumbricoides, Trichuris tricuria, Ancylostoma duodenale, Necator americanus, Hymenolepsis nana, rotaviruses, human caliciviruses, astroviruses, and cytolomegaloviruses.

[0095] The enteric pathogen may be selected from the group consisting of Trichomonas hominis, Giardia intestinalis, Giardia lamblia, Cryptosporidium parvum, Isospora berri, Dientamoeba, Microsporidia, Strongyloides stercoralis, Angiostrongylus costaricanus, Schistosoma mansoni, Schistosoma japonicum, Cyclospora cayetanensis, Enterocytozoon biennis, Enterocytozoon helium, Encephalitozoon intestinalis, Encephalitozoon cuniculi, Ascaris lumbricoides, Trichocris triculi, Ancylostoma dubini, Ancylostoma americanum, Dictyostelium nigricans, Rotavirus, Human calicivirus, Astrovirus, Cytomegalovirus.

[0096] The enteric pathogen may be selected from the group consisting of Campylobacter jejuni, Campylobacter coli, Enterococcus faecalis, and Enterococcus faecium.

[0097] The subject at risk of diarrhea may be a subject with food allergy, a subject administered antibiotics, a subject treated with radiation therapy, a subject treated with a pharmacological agent (e.g., as described herein), a subject with colectomy, colon cancer, ulcerative colitis, necrotizing enterocolitis, Crohn's disease, and / or a subject with an enteropathogen infection. The subject at risk of diarrhea may be, for example, a subject living in an area with limited or no access to clean drinking water, a subject living in an area where disease outbreaks occur, or a subject exposed to another person with acute diarrhea. The subject at risk of diarrhea may be a subject who is malnourished. Treating a subject at risk of diarrhea may be to reduce or prevent the occurrence of diarrhea (e.g., acute diarrhea) in the subject.

[0098] The term "prevention" in relation to diarrhea refers to reducing or eliminating the symptoms of diarrhea before they occur.

[0099] For example, preventing diarrhea can include reducing in a treated subject: (1) the incidence, onset, or formation of diarrhea, (2) the onset, duration, and / or severity of diarrhea symptoms (e.g., fever, bloody stool, vomiting) if disease develops, (3) mortality associated with acute diarrhea, or (4) a combination thereof. For each embodiment, the amount of reduction can be about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or about 100% in treated subjects compared to untreated subjects, respectively.

[0100] The diarrhea referred to herein is preferably not caused by Vibrio cholerae infection. Vibrio cholerae is a pathogen of the adult population and is typically absent in infants or young children. This has been reported, for example, for a Bangladeshi cohort (see Taniuchi M, et al. J Infect Dis. 2013). Suitably, a determination that a diarrheal episode is not caused by Vibrio cholerae infection can be achieved by testing a stool sample taken from the subject during the diarrheal episode, for example using metagenomics sequencing and / or 16S rRNA sequencing analysis, to determine the absence or essential absence of Vibrio cholerae in the sample.

[0101] Suitably, the diarrhea referred to herein is not caused by a Clostridioides difficile infection. Suitably, determining that a diarrheal episode is not caused by a Clostridioides difficile infection can be accomplished by testing a stool sample collected from the subject during a diarrheal episode, for example using metagenomics sequencing and / or 16S rRNA sequencing analysis, to determine the absence or essential absence of Clostridioides difficile in the sample.

[0102] Suitably, the diarrhea referred to herein is not caused by Vibrio cholerae or Clostridioides difficile infection.

[0103] Infant or toddler formula Suitably, the infant or toddler may be under about 60 months of age. For example, the infant or toddler may be under 48 months of age or under 36 months of age.

[0104] Suitably, the infant or toddler may be between about 1 and 60 months old, between about 1 and 48 months old, between about 2 and 60 months old, between about 2 and 48 months old, between about 2 and 36 months old, between about 4 and 36 months old, or between about 6 and 36 months old.

[0105] For example, the infant or toddler can be at least about 6 months old, at least about 10 months old, at least about 12 months old, at least about 14 months old, at least about 16 months old, at least about 20 months old, at least about 24 months old, or at least about 36 months old.

[0106] Suitably, the infant or toddler may be about 6 to about 60 months old, about 6 to about 48 months old, about 6 to about 36 months old. Suitably, the infant or toddler may be about 10 to about 60 months old, about 10 to about 48 months old, about 10 to about 36 months old.

[0107] An infant can be a child under 12 months of age. A "toddler" can be a child between 1 and 5 years of age, or between 1 and 3 years of age.

[0108] The subject may be a mammal. Preferably, the subject is a human. Unless otherwise specified, ages referred to herein relate to human subjects.

[0109] Blautia obeum Blautia species are obligately anaerobic, nonmotile, 1.0-1.5 x 1.0-3.0 μm in size, usually spherical or ellipsoidal, occurring in pairs or chains, and most strains are sporeless. The optimum temperature and pH for most Blautia strains are 37°C and 7.0, respectively. Carbohydrate utilization experiments have shown that all Blautia strains can use glucose, but different strains show different abilities to use sucrose, fructose, lactose, maltose, rhamnose, and raffinose. The end products of glucose fermentation by Blautia are acetate, succinate, lactate, and ethanol, and major biochemical tests have shown negative results for lecithin, lipase, catalase, and indole.

[0110] Blautia obeum is known to metabolize fiber in the gut and produce metabolic products such as propionate, thus contributing to a decrease in pH in the colonic lumen (see Lawson et al.; Int J Syst Evol Microbiol. 2015;65:789-793 and Nguyen et al.; Microbiome;2020 18:118).

[0111] The type strain of Blautia obeum is ATCC 29174. The reference genome of Blautia obeum is provided by GenBank assembly accession: GCA_003457595.1.

[0112] Suitably, Blautia obeum may comprise a 16S rRNA gene sequence having a cutoff identity value of 99% and a minimum query and target coverage of 80% when compared to the 16S rRNA sequences of ATCC 29174 and / or GCA_003457595.1 using BLASTn. Suitable comparisons may be performed using known methods, such as those described in Maturana and Cardenasm (Front Microbiol. 2021;660920).

[0113] Suitably, the Blautia obeum microorganism may have an ANI (average nucleotide identity) of at least 95%, a TETRA (tetranucleotide frequency) of at least 0.99, and / or an AAI (average amino acid identity) of at least 95% for the whole genome data set compared to ATCC 29174 and / or GCA_003457595.1. Suitably, the Blautia obeum microorganism may have an ANI (average nucleotide identity) of at least 95%, a TETRA (tetranucleotide frequency) of at least 0.99, and an AAI (average amino acid identity) of at least 95% for the whole genome data set compared to ATCC 29174 and / or GCA_003457595.1. Suitable comparisons may be performed using known methods, for example those described by Maturana and Cardenasm (supra).

[0114] Suitably, Blautia obeum can be identified using metagenomics methods. Suitable metagenomics methods can be performed, for example, using shotgun sequencing data. Metagenomics methods can also advantageously allow for the estimation of the relative abundance of organisms. Suitable metagenomics methods are known in the art, for example, MetaPhLaN 3.0 (see Beghini et al.; eLife 2021; 10: e65088; https: / / huttenhower.sph.harvard.edu / metaphlan).

[0115] In some embodiments, Blautia obeum is isolated from a human.

[0116] Suitably, "increasing / enhancing Blautia obeum" means increasing the absolute or relative number of Blautia obeum in the gut microbiota. For example, the nutritional composition may assist or support the growth and / or survival of the microorganism. Alternatively, the probiotic composition for use in the present disclosure comprises Blautia obeum, thereby increasing the number of Blautia obeum in the gut microbiota.

[0117] The abundance of Blautia obeum in the gut microbiota can be determined by assessing the relative abundance of Blautia obeum in a sample from a subject, for example, using the metagenomics methods described herein.

[0118] The level of Blautia obeum may be compared to a baseline value determined prior to administration of a composition described herein. The baseline value may be determined prior to the first administration of a composition described herein, or may be determined after the first administration of a composition described herein, but prior to any subsequent administrations.

[0119] Such methods are typically performed outside the human or animal body, for example on a sample previously obtained from the subject to be tested. Preferably, the sample is a faecal sample.

[0120] For example, the composition may increase the abundance of Blautia obeum by at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 50-fold, or 100-fold, e.g., compared to the abundance of Blautia obeum prior to administration of the composition.

[0121] Advantageously, increasing / enhancing the abundance and / or activity of Blautia obeum in the gut microbiota may increase the levels of autoinducer-2 (AI-2; (3aS,6S,6aR)-2266a-tetrahydroxy-3a-methyltetrahydro-2H-furo[2,3-d]

[0132] dioxaborole-2-ide) in the microbiome. AI-2 is a furanosyl borate diester and a member of a family of signaling molecules used in quorum sensing. AI-2 is generated by the reaction of enzymatically produced 1-deoxy-3-dehydro-D-ribulose with boric acid. AI-2 is produced by Blautia obeum and reduces colonization and virulence of Vibrio cholerae (Hsiao et al; Nature; 2014; 515(7527):423-426). AI-2 is known to regulate many bacterial functions, including pathogenic species (see Pereira CS, et al. FEMS Microbiol Rev. 2013). AI-2 levels can be measured using methods described in the art (see Campagna et al.; Anal. Chem. 2009, 81, 15, 6374-6381). AI-2 can also be measured by detecting precursors, such as 4,5-dihydroxy-2,3-pentanedione (DPD). This may be done, for example, by LC / MS untargeted metabolomics, as in this example.

[0122] Advantageously, increasing / enhancing Blautia obeum abundance and / or activity in the gut microbiota increases the levels of Nisin O (NSO) (Gherghisan-Filip C, et al. Sci Rep., 2018). NSO is a lantibiotic (modified peptide) for multiple Clostridium species (see Liu X, et al. Gut Microbes. 2021).

[0123] Suitably, increasing / enhancing Blautia obeum abundance and / or activity in the gut microbiota increases its bile salt hydrolase activity, which provides a mechanism of action against infections with, for example, V. cholerae (Alavi S., et al., Cell. 2020), C. perfringens (Liu X, et al. Gut Microbes. 2021 & Gherghisan-Filip C, et al. Sci Rep. 2018) and Clostridioides difficile (Mullish BH, et al. Gut. 2019).

[0124] Microbiota and Microbiome "Gut microbiota" may refer to the composition of microorganisms (including bacteria, archaea, and fungi) that inhabit the digestive tract.

[0125] The term "gut microbiome" may encompass both the "gut microbiota" and their "theatre of activity", which may include their structural elements (nucleic acids, proteins, lipids, polysaccharides), metabolic products (signaling molecules, toxins, organic and inorganic molecules), and molecules produced by the coexisting host and structured by the surrounding environmental conditions (e.g., Berg, G., et al., 2020. Microbiome, 8(1), pp.1-22).

[0126] Thus, in this disclosure, the term "gut microbiome" may be used interchangeably with the term "gut microbiota."

[0127] method The disclosure further provides a method for predicting or assessing whether an infant or young child is at risk for diarrhea, the method comprising determining a level of Blautia obeum in one or more samples obtained from the infant or young child.

[0128] Without wishing to be bound by theory, the inventors believe that infants or young children with higher levels (e.g., abundance and / or activity) of Blautia obeum in their microbiome may have stronger immunity (e.g., greater protection against pathogens, greater recovery from pathogens).

[0129] The level of Blautia obeum may be compared to a reference value, with the comparison indicating a predicted risk for infant or child diarrhea. The term reference level is synonymous with "control level" and broadly includes data used by those skilled in the art to facilitate accurate interpretation of technical data.

[0130] The reference value may be based on the value (e.g., the mean) of Blautia obeum in a population of infants and / or young children known to be at risk for diarrhea or who have experienced multiple episodes of diarrhea (e.g., 3 or more diarrhea episodes over a 24 month period, e.g., over the period from 0 to 24 months of age, or over the period from 10 to 24 months of age). The reference value may be based on the value (e.g., the mean) of Blautia obeum in a population of infants and / or young children known to be not at risk for diarrhea or who have not experienced multiple episodes of diarrhea (e.g., had 3 or more diarrhea episodes from 0 to 24 months of age or from 10 to 24 months of age). The reference value may be based on the value (e.g., the mean) of Blautia obeum in a population of infants and / or young children known to be not at risk for diarrhea or who have not experienced multiple episodes of diarrhea (e.g., had 0 diarrhea episodes from 0 to 24 months of age or from 10 to 24 months of age).

[0131] The reference levels may be matched to the age of the test sample.

[0132] Suitably, the infant or toddler may be between about 1 and 60 months old, between about 1 and 48 months old, between about 2 and 60 months old, between about 2 and 48 months old, between about 2 and 36 months old, or between about 4 and 36 months old, or between about 6 and 36 months old.

[0133] Preferably, the infant or toddler may be at least 10 months old.

[0134] For example, the infant or toddler can be at least about 10 months old, at least about 12 months old, at least about 14 months old, at least about 16 months old, at least about 20 months old, at least about 24 months old, or at least about 36 months old.

[0135] Preferably, the infant or toddler can be from about 10 to about 48 months old, from about 10 to about 36 months old, from about 10 to about 24 months old, or from about 10 to about 18 months old.

[0136] Risk of diarrhea, as used herein, can refer to the risk of multiple episodes of diarrhea over a given period of time, for example, 3 or more episodes of diarrhea from 0-24 months of age or from 10-24 months of age.

[0137] The method is typically carried out outside the human or animal body, for example on a sample previously obtained from the subject to be tested. Preferably, the sample is a faecal sample.

[0138] Suitably the method provides that a difference between the level of Blautia obeum in the test sample and the reference level is indicative of a risk of diarrhoea. Suitably the method may provide that a difference between the level of Blautia obeum in the test sample and the reference level is indicative of an increased risk of diarrhoea.

[0139] For example, a difference of 1.1-fold, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 50-fold, or 100-fold between the level measured in the test sample and the reference level may indicate an increased risk of diarrhea.

[0140] Suitably the method further comprises combining the level of Blautia obeum with one or more anthropometric measures.

[0141] Preferably, the diarrhea is not caused by Vibrio cholerae infection and / or Clostridioides difficile infection.

[0142] Suitably, infants or young children determined to be at risk for diarrhea using the methods of the present invention may be treated with a composition for reducing the incidence of diarrhea and / or preventing diarrhea according to the present disclosure.

[0143] Embodiment Various preferred features and embodiments of the present invention are described with reference to the following numbered paragraphs.

[0144] 1. A composition for use in reducing the incidence of and / or preventing diarrhea in an infant or young child, which composition increases / enhances Blautia obeum in the infant or young child's gut microbiota.

[0145] 2. A composition for use according to paragraph 1, comprising at least one arabinoxylan or arabinoxylan-containing material in an amount effective to increase / enhance Blautia obeum in the gut microbiota of an infant or young child.

[0146] 3. The composition for use according to paragraph 2, wherein the arabinoxylan or arabinoxylan-containing material is selected from the group consisting of: (i) whole corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan.

[0147] 4. A composition for use according to any of paragraphs 1 to 3, comprising a Blautia obeum microorganism.

[0148] 5. A composition for treating diarrhea, reducing the incidence of diarrhea, and / or preventing diarrhea in an infant or young child, comprising at least one arabinoxylan or arabinoxylan-containing material in an amount effective to increase / enhance Blautia obeum in the gut microbiota of the infant or young child.

[0149] 6. The composition described in paragraph 5, comprising at least one arabinoxylan or arabinoxylan-containing material selected from the group consisting of (i) whole kernel corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole kernel wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan, in an amount effective to increase / enhance Blautia obeum in the gut microbiome of an infant or young child.

[0150] 7. A composition comprising a Blautia obeum microorganism for treating diarrhea, reducing the incidence of diarrhea, and / or preventing diarrhea in an infant or young child.

[0151] 8. An arabinoxylan or an arabinoxylan-containing material for use in reducing the incidence of diarrhea and / or preventing diarrhea in an infant or young child, wherein the arabinoxylan increases / enhances Blautia obeum in the intestinal microbiota of the infant or young child.

[0152] 9. Arabinoxylan or arabinoxylan-containing material for use according to paragraph 8, wherein the arabinoxylan or arabinoxylan-containing material is selected from the group consisting of (i) whole kernel corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole kernel wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan.

[0153] 10. A Blautia obeum microorganism for use in reducing the incidence of and / or preventing diarrhea in an infant or young child.

[0154] 11. The composition for use according to any of paragraphs 1 to 10, wherein the diarrhea is not caused by Vibrio cholerae, arabinoxylan or arabinoxylan-containing material or Blautia obeum microorganism.

[0155] 12. The composition, arabinoxylan or arabinoxylan-containing material or Blautia obeum microorganism for use according to any of paragraphs 1 to 11, wherein the infant or young child is less than about 60 months of age, preferably less than 36 months of age, preferably from about 6 months to about 36 months of age.

[0156] 13. A composition for use according to any of paragraphs 1 to 12, an arabinoxylan or an arabinoxylan-containing material, or a Blautia obeum microorganism, wherein an infant or young child has been determined to be at risk of developing diarrhea.

[0157] 14. The composition, arabinoxylan or arabinoxylan-containing material or Blautia obeum microorganism for use according to any of paragraphs 1 to 13, wherein the diarrhea is caused by at least one of an enteric pathogen infection, a food allergy, or the use of an antibiotic.

[0158] 15. Enteric pathogens include Campylobacter jejuni, Campylobacter coli, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Salmonella enterica, Shigella flexneri, Shigella sonnei, Shigella dysenteriae, Campylobacter upsaliensis, Yersinia enterocolitica, Yersinia pseudotuberculosis, Vibrio parahaemolyticus, Clostridium difficile, Entamoeba histolytica, Entamoeba dispar, Endolimax nana, Rhodamoeba butzii, Trichomonas meningitidis, Blastocystis hominis, Trichomonas hominis, Giardia intestinalis, Giardia lamblia, and Chlamydia trachomatis. 15. The composition for use according to paragraph 14, the arabinoxylan or arabinoxylan-containing material or the Blautia obeum microorganism is selected from the group consisting of Ptosporidium parvum, Isospora belli, Dientamoeba, Microsporidia, Strongyloides stercoralis, Angiostrongylus costaricanus, Schistosoma mansoni, Schistosoma japonicum, Cyclospora cayetanensis, Enterocytozoon bieneusi, Enterocytozoon helium, Encephalitozoon intestinalis, Encephalitozoon cuniculi, Ascaris lumbricoides, Trichoderma trichoderma, Ancylostoma dubini, Ancylostoma americanum, Dictyostelium nigricans, Rotavirus, Human calicivirus, Astrovirus, Cytomegalovirus, and combinations thereof.

[0159] 16. The composition for use according to paragraph 15, arabinoxylan or arabinoxylan-containing material or Blautia obeum microorganism, wherein the enteric pathogen is selected from the group consisting of Campylobacter jejuni, Campylobacter coli, Enterococcus faecalis, Enterococcus faecium, and combinations thereof.

[0160] 17. The composition for use according to paragraph 14, wherein the intestinal pathogen is selected from the group consisting of Trichomonas hominis, Giardia intestinalis, Giardia lamblia, Cryptosporidium parvum, Isospora belli, Dientamoeba, Microsporidia, Strongyloides stercoralis, Angiostrongylus costaricanus, Schistosoma mansoni, Schistosoma japonicum, Cyclospora cayetanensis, Enterocytozoon biennis, Enterocytozoon helium, Encephalitozoon intestinalis, Encephalitozoon cuniculi, Ascaris lumbricoides, Trichocris triculia, Ancylostoma dubini, Ancylostoma americanum, Dictyostelium nigricans, Rotavirus, Human calicivirus, Astrovirus, Cytomegalovirus, and combinations thereof. 17. The composition for use according to paragraph 14, wherein the intestinal pathogen is selected from the group consisting of Trichomonas hominis, Giardia intestinalis, Giardia lamblia, Cryptosporidium parvum, Isospora belli, Dientamoeba, Microsporidia, Strongyloides stercoralis, Schistosoma costaricanus, Schistosoma japonicum, Cyclospora cayetanensis, Enterocytozoon biennis, Enterocytozoon helium, Encephalitozoon intestinalis, Encephalitozoon cuniculi, Ascaris lumbricoides, Trichocris triculia, Ancylostoma dubini, Ancylostoma americanum, Dictyostelium nigricans, Rotavirus, Human calicivirus, Astrovirus, Cytomegalovirus, and combinations thereof.

[0161] 18. The composition for use according to any of paragraphs 1 to 17, arabinoxylan or arabinoxylan-containing material or Blautia obeum microorganism, wherein the diarrhea is not caused by Clostridioides difficile infection.

[0162] 19. A composition for use according to any of paragraphs 1 to 18, wherein the composition is a dietary or nutritional composition.

[0163] 20. A dietary or nutritional composition comprising: 20. The composition for use according to paragraph 19, selected from the group consisting of foods, beverages, powdered supplements, infant or toddler formulas, compositions for infants or toddlers intended to be added to or diluted in breast milk, such as breast milk fortifiers, foods intended for consumption by infants or toddlers, alone or in combination with breast milk, such as food supplements, and combinations thereof.

[0164] 21. A composition for use according to paragraph 19 or 20, wherein the dietary or nutritional composition further comprises dark chocolate.

[0165] 22. A method for reducing the incidence of diarrhea and / or preventing diarrhea in an infant or young child subject, comprising administering to an infant or young child in need thereof a composition that increases / enhances Blautia obeum in the gut microbiota.

[0166] 23. The method of paragraph 22, wherein the composition comprises at least one arabinoxylan or arabinoxylan-containing material, preferably at least one arabinoxylan or arabinoxylan-containing material selected from the group consisting of: (i) whole kernel corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole kernel wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan, in an amount effective to increase / enhance Blautia obeum in the infant or young child's gut microbiome.

[0167] 24. A method for treating diarrhea, reducing the incidence of diarrhea, and / or preventing diarrhea in an infant or young child, comprising administering to an infant or young child in need thereof at least one arabinoxylan or arabinoxylan-containing material, or a composition comprising at least one arabinoxylan or arabinoxylan-containing material, in an amount effective to increase / enhance Blautia obeum in the infant's or young child's gut microbiome, wherein the at least one arabinoxylan or arabinoxylan-containing material is selected from the group consisting of: (i) whole kernel corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan.

[0168] 25. A composition comprising a combination of Blautia obeum probiotics and at least one arabinoxylan or arabinoxylan-containing material selected from the group consisting of: (i) whole kernel corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan, wherein the combination is in an amount effective to treat diarrhea, reduce the incidence of diarrhea, and / or prevent diarrhea in an infant or young child.

[0169] 26. The composition according to paragraph 25, wherein the diarrhea is not caused by Vibrio cholerae infection.

[0170] 27. A Blautia obeum probiotic for use in reducing the incidence of and / or preventing diarrhea in an infant or young child, wherein the diarrhea is not caused by Vibrio cholerae infection.

[0171] 28. A method for predicting whether an infant or young child is at risk for diarrhea, the method comprising determining the presence of Blautia obeum in one or more samples obtained from the infant or young child. EXAMPLES

[0172] The compositions and methods according to the present disclosure will now be further illustrated by examples, which are intended to aid those skilled in the art in practicing the disclosure and are not intended to limit the scope of the disclosure in any way.

[0173] Example 1: Microbiota and health studies The microbiome and health trial is described in Vidal et al. (https: / / www.medrxiv.org / content / 10.1101 / 19000505v1) and is registered at clinicaltrials.gov as NCT02361164.

[0174] Briefly, the following information was collected for n=220 infants or toddlers: anthropometric measurements, diarrhea and acute respiratory infections (ARI), medication including antibiotic use, feeding status, weaning food, nasopharyngeal and fecal pathogen and microbiota profiles, secretory status (FUT2, FUT3). Fecal samples for microbiota analysis were collected at birth, 2 months, 6 months, 10 months, 15 months, 18 months, and 24 months. Growth results were recorded at birth, 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, 15 months, 18 months, and 24 months. See Figure 1 for an overview.

[0175] Example 2: Definition of a healthy reference population The profile of diarrhea episodes in the microbiota and health study was evaluated. Healthy and unhealthy diarrhea outcomes were assigned according to a cumulative score of diarrhea incidence from 0 to 24 months of age. Healthy infants were defined as those with zero diarrhea episodes by 24 months of age, and unhealthy infants were defined as those with three or more diarrhea episodes by 24 months of age (see Figure 2).

[0176] Example 3: Differences in Blautia obeum between healthy and unhealthy humans The diarrhea outcome of 0 vs. ≥3 episodes at age 0–24 months was associated with Blautia obeum levels in fecal samples (cumulative score of diarrhea occurrence) (see Figures 3A, 3B). Furthermore, a longitudinal, permutation-based analysis using the methodology of Metwally AA et al. (Microbiome;2018;6(32)) identified statistically significant differences in abundance of Blautia obeum levels in fecal samples from infants or toddlers with 0 diarrhea compared to those with ≥3 diarrhea episodes (cumulative score at age 10–24 months) (see Figures 4A, 4B).

[0177] A total of 56 samples were collected during actual diarrheal episodes. Metagenomic sequencing of these samples from multiple infants or young children (n=18) at different time points was performed using the MetaPhLaN 3.0 pipeline (Beghini et al.; eLife 2021;10:e65088; see https: / / huttenhower.sph.harvard.edu / metaphlan).

[0178] Mainly, the pathogen Campylobacter jejuni was identified, with non-zero values ​​in 23 samples (min -0.0000256, max -0.32588493, median -0.0015, mean -0.0333, maximum possible relative abundance is 1.0). Other pathogens such as Campylobacter coli (present in 3 samples), Enterococcus faecalis (present in 1 sample), and Enterococcus faecium (present in 11 samples - min -0.0000437, max -0.110366511, median -0.0016934, mean -0.020927274 relative abundance, again maximum possible relative abundance is 1.0) were identified.

[0179] For Vibrio cholerae, most diarrheal samples had a relative abundance value of 0.0 (the maximum possible value is 1.0). Only two samples had a non-zero relative abundance value for Vibrio cholerae (0.04785131, 0.0034564). Furthermore, Clostridioides difficile had a relative abundance of 0.0 in all of these diarrheal samples.

[0180] Example 4: Bacterial quorum sensing signals Levels of autoinducer-2 (AI-2), a quorum-sensing molecule produced by Blautia obeum, were assessed by LC / MS untargeted metabolomics in fecal samples from the Dhaka cohort.

[0181] The presence of AI-2 was assessed using 4,5-dihydroxy-2,3-pentanedione (DPD), a precursor of AI-2, as a proxy. When using LC / MS-based untargeted metabolomics, molecules in biological samples are ionized into different molecular adducts depending on the solvent used for molecular extraction and the ionization mode employed during analysis. The most common adducts are hydrogen adducts (M+H, MH MH-H2O (water removed)), sodium adducts (M+Na), potassium adducts (M+K) and ammonium adducts (M+NH4+). The theoretical molecular weight of DPD in the adduct form was calculated and compared with the mass of metabolic features detected in the fecal metabolome dataset. The selection criterion for identifying a match between DPD adducts and metabolic features was set at a mass difference of less than 5 ppm.

[0182] Three metabolic features (QI31895, QI19815, QI4308) were putatively assigned as DPD because their masses matched those of DPD adducts (MH&M+K) with a mass difference of less than 1 ppm.

[0183] A linear model including time as a cofactor showed a significant negative association between the metabolic trait QI31895 (nominal coeff pval=0.0055) and diarrhea incidence. The same metabolic trait was significantly lower in infants with 3 or more episodes of diarrhea than in infants with no episodes of diarrhea at 18 months of age (nominal p-value: 0.038 Mann-Whitney U test).

[0184] Example 5: Predicting the risk of diarrhea caused by Blautia obeum A machine learning-based model was used to determine whether Blautia obeum predicts the onset of diarrhea (DIA). We calculated the difference between the cumulative number of DIA events at 24 and 10 months of age, as described above. We stratified the infants into two groups, denoted as 0 (if there were 0 DIA events) and 1 (if there were any DIA events). We ran a set of parameter-optimized random forest cross-sectional models to detect where Blautia abundance was discriminatory for DIA outcomes in the models, and then assessed its relative feature importance. In the family of models created, Blautia obeum was generally considered to be in the top 15 of important features for the selected models, with an F1 score of approximately 0.6 in the test set. The best time points for predicting diarrhea status were 15 and 18 months of age. An example of such results is shown in Figure 5. In Figure 5, Blautia was found to be the second most important bacterial feature for predicting diarrhea outcomes at infant age 18 months of age.

[0185] Example 6: Effect of wheat arabinoxylan on the infant microbiome Samples were tested with either NSC (negative control), IN (inulin positive control), W (wheat arabinoxylan) or C (irrelevant fibre) (2 g / L of each product).

[0186] Wheat arabinoxylan significantly increased acetic acid (Figure 9) and propionic acid (Figure 10) (and therefore total SCFA (short chain fatty acids) (Figure 8) levels), reduced pH (Figure 7) and increased gas production.

[0187] In particular, a decrease in pH and an increase in propionate levels are expected effects along with increasing Blautia obeum levels.

[0188] Quantitative shallow shotgun sequencing is performed to confirm Blautia obeum levels in each sample.

[0189] Materials and Methods Fecal samples were collected according to a procedure approved by the Ethics Committee of the Ghent University Hospital. Donor selection criteria were as follows: 6 donors aged 6 (± 1) months, 6 donors aged 12 (± 1) months, exclusively breastfed until 4 months of age and already introduced complementary feeding. Exclusion criteria were the use of antibiotics within 90 days prior to sample delivery for the study and a history of NEC or intestinal surgery. Thus, 12 specific subjects were enrolled.

[0190] Colonic fermentation of the test products by the gut microbiota in the fecal samples was evaluated 24 h after inoculation. Acetic acid, propionic acid, butyric acid, valeric acid and branched chain fatty acids (bCFA) (sum of isobutyric acid, isovaleric acid and isocaproic acid) were measured by a GC-FID approach. Lactic acid was measured by a high-throughput spectrophotometric method. In addition, pH and gas production were measured as important markers of microbial metabolic activity.

[0191] For statistical evaluation of treatment effects on basic fermentation parameters, cell counts, microbial diversity, and microbial composition (phylum level) across infants (all 12 infants or across 6 infants within each age group), repeated measures ANOVA analyses were performed (based on paired t-tests, thus accounting for the fact that values ​​are compared between samples of a given donor). The statistical significance of possible treatment effects was tested by Benjamini-Hochberg post-hoc tests.

[0192] For quantitative shallow shotgun sequencing, normalized Illumina libraries were prepared upon DNA extraction, followed by 3M total DNA sequencing.

[0193] All publications mentioned in the above specification are incorporated herein by reference.Various modifications and alterations of the methods, compositions and uses disclosed in this disclosure will be apparent to those skilled in the art without departing from the scope and spirit of this disclosure.Although this disclosure is disclosed in connection with certain preferred embodiments, it should be understood that the disclosure claimed should not be unduly limited to such specific embodiments.Indeed, various modifications of the disclosed modes for carrying out the disclosure will be apparent to those skilled in the art and are intended to be within the scope of the following claims.

Claims

1. 1. A composition for use in the treatment, reduction of the incidence and / or prevention of diarrhea in an infant or young child, which composition increases / enhances Blautia obeum in the intestinal microbiota of said infant or young child.

2. 2. A composition for use according to claim 1 comprising at least one arabinoxylan or arabinoxylan-containing material in an amount effective to increase / enhance Blautia obeum in the intestinal microbiota of said infant or young child.

3. 1. An arabinoxylan or an arabinoxylan-containing material for use in the treatment of diarrhea, reducing the incidence of diarrhea and / or preventing diarrhea in an infant or young child, wherein said arabinoxylan increases / enhances Blautia obeum in the intestinal microbiota of said infant or young child.

4. 4. The composition for use or arabinoxylan or arabinoxylan-containing material according to claim 2 or 3, wherein the arabinoxylan or arabinoxylan-containing material is selected from the group consisting of: (i) whole kernel corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole kernel wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan.

5. A composition for use according to any one of claims 1 to 4, comprising a Blautia obeum microorganism.

6. 1. A Blautia obeum microorganism for use in the treatment, reduction of the incidence of and / or prevention of diarrhea in an infant or young child.

7. The composition for use, arabinoxylan or arabinoxylan-containing material or Blautia obeum microorganism according to any one of claims 1 to 6, wherein the diarrhea is not caused by Vibrio cholerae.

8. The composition for use, arabinoxylan or arabinoxylan-containing material or Blautia obeum microorganism according to any one of claims 1 to 7, wherein the infant or toddler is less than about 60 months of age, preferably less than 36 months of age, preferably from about 6 to about 36 months of age.

9. 9. The composition for use, arabinoxylan or arabinoxylan-containing material or Blautia obeum microorganism according to any one of claims 1 to 8, wherein the diarrhea is caused by at least one of an enteric pathogen infection, a food allergy or the use of an antibiotic.

10. The composition for use, arabinoxylan or arabinoxylan-containing material or Blautia obeum microorganism according to any one of claims 1 to 9, wherein the diarrhea is not caused by a Clostridioides difficile infection.

11. 11. A composition for use according to any one of claims 1 to 10, wherein the composition is a dietary or nutritional composition, suitably selected from the group consisting of a food, a beverage, a powder supplement, an infant or toddler formula, a composition for infants or young children intended to be added to or diluted in breast milk, such as a breast milk fortifier, a food intended to be consumed by an infant or young child, alone or in combination with breast milk, such as a food supplement, and combinations thereof.

12. 1. A method for treating diarrhea, reducing the incidence of diarrhea and / or preventing diarrhea in an infant or young child subject, comprising administering to an infant or young child in need thereof a composition that increases / enhances Blautia obeum in the gut microbiota.

13. 13. The method of claim 12, wherein the composition comprises at least one arabinoxylan or arabinoxylan-containing material, preferably at least one arabinoxylan or arabinoxylan-containing material selected from the group consisting of: (i) whole kernel corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole kernel wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan, in an amount effective to increase / enhance Blautia obeum in the infant or young child's gut microbiome.

14. 1. A composition comprising a combination of Blautia obeum probiotics and at least one arabinoxylan or arabinoxylan-containing material, preferably the at least one arabinoxylan or arabinoxylan-containing material is selected from the group consisting of: (i) whole kernel corn, (ii) corn arabinoxylan, (iii) corn bran, (iv) corn bran arabinoxylan, (v) whole wheat, (vi) wheat arabinoxylan, (vii) wheat bran, and (viii) wheat bran arabinoxylan, wherein the composition comprises the combination in an amount effective to treat, reduce the incidence of, and / or prevent diarrhea in an infant or young child, preferably wherein the diarrhea is not caused by a Vibrio cholerae infection.

15. 1. A Blautia obeum probiotic for use in reducing the incidence of and / or preventing diarrhea in an infant or young child, wherein said diarrhea is not caused by a Vibrio cholerae infection.

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