Risk of allergy and nutrients for reducing the risk

Abstract

A method for predicting the risk of developing eczema is provided, based on the differences in the development of the microbiome and its metabolites between healthy infants and infants with eczema, and based on this finding, a nutritional remedy is provided in the form of lactate-utilizing bacteria and fiber that stimulates lactate-utilizing bacteria.

Description

[0001] This application is a divisional application. The original application was filed on June 12, 2017, with application number 201780048330.X (international application number PCT / EP2017 / 064233), entitled "Risk of allergy and nutrients for reducing such risk". Technical Field

[0002] This invention pertains to the field of allergies, particularly eczema; and relates to a method for assessing the risk of developing allergies in early life. The invention also relates to nutritional remedies for reducing the risk of developing allergies. Background Technology

[0003] The development of the early gut microbiota is a dynamic process that can influence lifelong health. Abnormalities in this process are associated with the formation of allergic diseases, but the exact microbial pattern remains unclear. The gradual diversification into a relatively stable, adult-like composition is a dynamic process influenced by environmental factors such as birth pattern, gestational age at birth, and early-life nutrition. The importance of pioneering microbes is particularly evident, as changes in colonization are associated with an increase in allergic diseases in affluent societies. To date, research has focused on the accelerated ecological succession of the gut microbiota in allergic infants to achieve a more typical adult community structure. Allergic diseases with varying symptoms include the most common chronic diseases in children in developed countries. Atopic dermatitis is often the first allergic symptom to appear, followed by other allergic symptoms; this process is called the allergic march, also known as the atopic process.

[0004] First, facultative anaerobic bacteria (such as Enterobacteriaceae) grow rapidly on monosaccharides. Enterobacteriaceae Gradually replaced by anaerobic bacteria (such as Bifidobacterium spp.) Bifidobacterium ) and Bacteroides ( Bacteroides Human milk replaces certain microbiota. With the introduction of solid foods into the diets of infants aged 4-6 months, the microbiota further diversifies, establishing more strict anaerobes, such as adult Clostridium clusters IV and XIVa. Given the simultaneous maturation of the immune system, from the perspective of microbial composition and activity, species succession and the establishment of a stable adult community in early life are guided by human milk and are likely crucial. This early colonization and succession is considered to form a vital process that lays an optimal health foundation for later life.

[0005] Breastfeeding is believed to prevent allergies because many allergens and immune mediators present in human milk, as well as the high abundance of human milk oligosaccharides, are absent in synthetic milk. Several studies have been conducted using different types of infant formula (IF) supplemented with indigestible oligosaccharides (called prebiotics). Prebiotics are typically indigestible fibers that reach the colon intact and are known to selectively stimulate the growth and activity of specific beneficial members of the microbiome. In intervention trials using IFs supplemented with specific prebiotic oligosaccharides, a significantly reduced risk of eczema has been observed (Arslanoglu et al., 2012, J Biol Regulation & Homeostatic Agents 26:49-59; Grüber et al., 2010, J Allergy and Clinical Immunology 126:791-797; Moro et al., 2006, Archives of Disease in Childhood 91:814-819).

[0006] WO 2009 / 102199 discloses compositions comprising Bifidobacteria, galactooligosaccharides, and fructooligosaccharides, for introducing solid weaning foods into the diets of infants consuming infant formula or breast milk. US 2015 / 0352162 discloses compositions comprising live bacteria that utilize lactate to produce propionic acid and live lactate-producing bacteria, particularly infant food compositions, their preparation, and their use in treating digestive system disorders. US 2014 / 0341921 discloses human-derived bacterial species belonging to the class Clostridium that induce the accumulation of regulatory T cells (Treg cells) in the colon and suppress immune function, and pharmaceutical compositions containing these bacteria for the prevention and treatment of immune-mediated diseases, such as autoimmune diseases. Summary of the Invention

[0007] In clinical trials of infants at risk of developing atopic diseases, the composition of the fecal microbiota and the development of its metabolites during the first 6 months of life were analyzed. Differences in the composition and development of the gut microbiota in early life were investigated in 18-month-old infants with and without eczema. Until 18 months of age, infants with eczema showed reduced access to lactate-utilizing bacteria, particularly at 26 weeks of age to Eubacteria (…). Eubacterium ) and anaerobic bacteria ( AnaerostipesAcquisition of lactic acid was reduced. Furthermore, in these infants, fecal lactic acid levels were lower at 4 and 12 weeks of age, but increased at 26 weeks of age when the infants began complementary feeding (introduction of solid foods). In infants without eczema, this pattern was reversed, as lactic acid levels were lower at week 26 compared to earlier time points.

[0008] This study is the first to demonstrate a link between the function of the gut microbiota and the expression of allergic phenotypes, particularly eczema, in infants. These observations suggest that microbial species succession patterns and metabolite cross-feeding have long-term health effects on the immune system during specific developmental stages in early life, particularly during the introduction of solid foods and weaning, which involves a more adult-like diet. Therefore, the risk of developing eczema later in life can be predicted based on lactate accumulation and / or a lower number of lactate-utilizing bacteria at 26 weeks of age. Furthermore, these observations contribute to the development of optimal nutritional strategies to support the clustering of lactate-utilizing bacteria in the gut for infants older than approximately 6 months. Subsequently, among the numerous fibers tested in in vitro fermentation experiments, only a few—inulin, polydextrose, and partially hydrolyzed guar gum—were able to stimulate lactate-utilizing anaerobic bacterial species (…). Anaerostipes The growth of spp. (spp.). Therefore, nutritional supplements or follow-up formulas or toddler formulas containing these fibers and bacteria that utilize lactate can help change the microbiome and its metabolism in a direction more similar to that of healthy infants who will not develop eczema later in life. Detailed Implementation

[0009] Therefore, in one aspect, the present invention relates to a nutritional composition comprising bacteria utilizing lactate and at least one type of fiber, said fiber being selected from fructooligosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more. Preferably, the nutritional composition is given to an infant or young child.

[0010] This invention also relates to a method for preventing or reducing the risk of allergies, the method being carried out by administering to an infant or young child a nutritional composition comprising lactate-utilizing bacteria and at least one type of fiber, said fiber being selected from fructosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more. For certain jurisdictions, this can also be expressed as: the use of bacteria and fiber in the preparation of a nutritional composition, administered to an infant or young child to prevent or reduce the risk of allergies, wherein said bacteria are lactate-utilizing bacteria, and said fiber is at least one type of fiber selected from: fructosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more. This invention can also be described as a nutritional composition for preventing or reducing the risk of allergies, preferably given to infants or young children, the nutritional composition comprising lactate-utilizing bacteria and at least one fiber selected from: fructosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more. Therefore, in other words, this invention relates to a nutritional composition comprising lactate-utilizing bacteria and at least one fiber selected from fructosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more, the nutritional composition preventing or reducing the risk of allergies by being given to infants or young children.

[0011] In a preferred embodiment of the nutritional composition of the present invention, or in the method or use of the present invention, the bacteria utilizing lactate are selected from the genus *Anaerobes* (…). Anaerostipes ) and Eubacterium ( Eubacterium ).

[0012] The present invention also relates to a method for preventing or reducing the risk of allergies, the method being carried out by administering a nutritional composition to an infant or young child, the nutritional composition comprising at least one fiber selected from the group consisting of fructooligosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more. For certain jurisdictions, this may also be expressed as the use of fiber in the preparation of the nutritional composition, the administration of the nutritional composition to an infant or young child to prevent or reduce the risk of allergies, wherein the fiber is at least one fiber selected from the group consisting of fructooligosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more. The present invention may also be expressed as a nutritional composition for preventing or reducing the risk of allergies, preferably administered to an infant or young child, the nutritional composition comprising at least one fiber selected from the group consisting of fructooligosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more. In this embodiment, the nutritional composition preferably further comprises lactate-utilizing bacteria. Preferably, the lactate-utilizing bacteria are selected from the genus *Anaerobes* (…). Anaerostipes ) and Eubacterium ( Eubacterium ) In a preferred embodiment of the invention, the nutritional composition is given or used on infants or young children who have an increased risk of developing allergies.

[0013] In a preferred embodiment, infants or young children with an increased risk of developing allergies are identified by the following methods: a. At the first point in time when the infant or toddler is approximately 3-17 weeks old, and b. At the second time point when the infant or toddler is approximately 20-35 weeks old. Determine the concentration and / or percentage of lactic acid in fecal material obtained from infants or young children, based on total organic acids, and c. Subsequently, determine whether the concentration and / or percentage of lactic acid in the fecal material, based on total organic acids, increased or decreased from the first time point to the second time point. Increased lactate levels indicate an increased risk of allergies in infants or young children, and / or can be identified by the following methods: a. At the first point in time when the infant or toddler is approximately 3-17 weeks old, and b. At the second time point when the infant or toddler is approximately 20-35 weeks old. The amount or relative amount of lactate-utilizing bacteria in fecal material obtained from infants or young children, and c. Subsequently, determine whether the amount or relative amount of bacteria utilizing lactate increased or decreased from the first time point to the second time point. A slight increase or decrease in the amount or relative amount of bacteria that utilize lactate indicates an increased risk of allergies in infants or young children.

[0014] In one aspect, the present invention also relates to a method for assessing whether an infant has an increased risk of developing allergies, the method comprising: a. At the first time point when the infant is approximately 3-17 weeks old, and b. At the second time point when the infant is approximately 20-35 weeks old The concentration and / or percentage of lactic acid in fecal material obtained from infants, based on total organic acids, were determined. c. Subsequently, determine whether the concentration and / or percentage of lactic acid in the fecal material, based on total organic acids, increased or decreased from the first time point to the second time point. Increased lactic acid levels indicate an increased risk of allergies in infants.

[0015] Similarly, the present invention also relates to a method for assessing whether an infant has an increased risk of developing allergies, the method comprising: a. At the first time point when the infant is approximately 3-17 weeks old, and b. At the second time point when the infant is approximately 20-35 weeks old The amount or relative amount of lactate-utilizing bacteria in fecal material obtained from infants or young children, and c. Subsequently, determine whether the amount or relative amount of bacteria utilizing lactate increased or decreased from the first time point to the second time point. A slight increase or decrease in the amount or relative amount of bacteria that utilize lactate indicates an increased risk of allergies in infants.

[0016] In all aspects and embodiments of the invention, allergies are preferably eczema.

[0017] Microbiota and their metabolites It has been found that the amount or relative amount of lactate-utilizing bacteria in the microbiota of 26-week-old infants with allergies (particularly eczema) is reduced compared to infants without allergies. Specifically, the amount and relative amount of anaerobic and eubacterial bacteria are reduced. Anaerobic bacteria include *Trichophyton* (…). Lachnospiraeceae This genus and species belongs to the family (family ) and is a strict anaerobic bacterium, a member of the human gut microbiota. It can utilize lactic acid as a carbon and energy source, primarily producing butyric acid. Known anaerobic species include: A. caccae, A butyraticus, A. hadrus and A. rhamnosivorans Eubacteria are Eubacteria ( Eubacteriaceae This family comprises genera and species of *Myxobacterium*, which are strictly anaerobic bacteria, and some species are members of the human gut microbiota. In particular, *Myxobacterium* is known to be... Eubacterium limosum) and Hodgkin's Eubacterium ( Eubacterium hallii Lactate is typically used to produce butyrate. In the method of the present invention for assessing whether an infant has an increased risk of developing allergies, preferably, the amount or relative amount of bacteria utilizing lactate is the amount or relative amount of bacteria utilizing lactate to produce butyrate. In the method of the present invention for assessing whether an infant has an increased risk of developing allergies, preferably, the amount of bacteria utilizing lactate is an anaerobic species ( ). Anaerostipes spp) and species of the genus Eubacterium ( Eubacterium The total amount of fecal anaerobic bacteria (spp). Preferably, it is fecal anaerobic corynebacteria (spp). Anaerostipes caccae ), Anaerostipes butyraticus , Anaerostipes hadrus , Anaerostipes rhamnosivorans , Eubacterium limosum and Eubacterium hallii The total amount. In one embodiment of the method of the present invention for assessing whether an infant has an increased risk of developing allergies, preferably, the amount of bacteria utilizing lactate is the total amount of anaerobic bacteria species, preferably fecal anaerobic Corynebacterium, Anaerostipes butyraticus , Anaerostipes hadrus and Anaerostipes rhamnosivorans The total amount. In one embodiment of the method of the present invention for assessing whether an infant has an increased risk of developing allergies, preferably, the amount of bacteria utilizing lactate is the total amount of Eubacterium species, preferably the total amount of Myxobacterium mucosae and Eubacterium hominis. In the context of the present invention, a small increase in the amount of bacteria utilizing lactate means an increment of less than 0.1% based on total bacteria. A small increase in the relative amount of bacteria utilizing lactate means an increment of less than 0.1%. Other bacteria utilizing lactate include Coccidia leucocephala (… Coprococcus catus ) and Veillonella ( Veillonella sp. These bacteria primarily produce propionate from lactate.

[0018] It has been found that, compared with infants without allergies, the amount and relative amount, or concentration and percentage, of D-lactic acid and L-lactic acid in the fecal material of 26-week-old infants with allergies (particularly eczema) are increased in the microbiota. The opposite is true at earlier ages, and in infants with allergies, lactic acid levels are lower at 4 weeks and 12 weeks of age or younger. In infants without allergies, the increased levels of acetate and lactate in early life at 4 and 12 weeks of age may be crucial for establishing lactate-utilizing bacteria by approximately 6 months of age. This suggests that microbial species succession and metabolite crossfeeding are essential for establishing a gut community and environment that supports the immune system during specific developmental stages of early life. Abnormal temporal dynamics regarding the microbiota (lactate-utilizing bacteria) and its metabolites (lactic acid levels) have been observed in infants with allergies in the first 18 months of life, up to 26 weeks of age. Therefore, remedial methods can be designed to improve these kinetics, making them similar to those found in infants without allergies, particularly eczema. Thus, in one embodiment, the present invention relates to a nutritional composition comprising bacteria that utilize lactate, preferably bacteria that utilize lactate to produce butyrate, preferably anaerobic bacteria and Eubacterium, more preferably at least one selected from fecal anaerobic Corynebacterium, Anaerostipes butyraticus , Anaerostipes hadrus , Anaerostipes rhamnosivorans , E hallii and E. limosum The bacteria. In one embodiment, preferably, the anaerobic bacteria are *Corynebacterium fecalithii*. As is known in the art, these species can be isolated from human feces or ordered from a culture collection center. As is known in the art, bacteria that utilize lactic acid can be cultured and dried. Preferably, the nutrient composition containing bacteria that utilize lactic acid contains 10 2 Up to 10 9 cfu, more preferably 10 3 Up to 10 6 CFU of lactate-producing bacteria / g dry weight.

[0019] Fiber that stimulates the growth of bacteria that utilize lactic acid In one embodiment, the present invention relates to a method for increasing the amount or relative amount of lactate-utilizing bacteria in the gut microbiota of an infant or young child, wherein the lactate-utilizing bacteria are preferably bacteria that utilize lactate to produce butyrate, preferably anaerobic bacteria and / or Eubacterium; the method comprises administering to the infant or young child at least one fiber selected from the group consisting of fructooligosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more.

[0020] As used herein, the term “degree of polymerization” (DP) refers to the number of monomer units linked together in a polymer or oligomer. When referring to polysaccharides, cellulose, or oligosaccharides, the term “soluble” means that, according to the method described in Prosky et al., JASSO Off Anal Chem, 1988, 71:1017-1023, at least 50% of the substance is soluble. Average degree of polymerization refers to the average degree of polymerization based on weight.

[0021] Preferably, the amount of fiber present in the nutritional composition is 0.2 to 8 g based on the dry weight of 100 g of the nutritional composition, more preferably 0.5 to 5 g based on the dry weight of 100 g, and is selected from fructooligosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more.

[0022] According to a particularly preferred embodiment, partially hydrolyzed guar gum (PHGG) is used as fiber to stimulate bacteria that utilize lactic acid or to prevent allergies. Guar gum is derived from guar beans (… Cyamopsis tetragonolobus Guar gum is a polysaccharide obtained from the endosperm of guar gum, primarily consisting of high-molecular-weight hydrocolloid polysaccharides composed of galactose and mannose units linked by glycosidic bonds. Specifically, guar gum is preferably composed of (1... 4) The linear chain of the β-D-pyranomannose unit and its relationship with (1) 6) Composed of α-D-galactopyranoyl units linked by bonds. PHGG is available under the trade name Benefiber® from Novartis Nutrition Corporation or under the trade name "Sunfiber® AG" from Taiyo Kagaku. Preferably, the hydrolyzed gel is in aggregated form, which has better solubility. DP is typically 10 to 300. Preferably, DP is 20 to 150, and even more preferably 25 to 100.

[0023] In the nutritional composition of the present invention, the fiber is selected from fructooligosaccharides, polydextrose and partially hydrolyzed guar gum, and preferably contains 0.2 to 8 g, or even more preferably 0.5 to 5 g of partially hydrolyzed guar gum, based on the dry weight of 100 g of nutritional composition.

[0024] According to a particularly preferred embodiment, fructooligosaccharides are used as fiber to stimulate bacteria that utilize lactic acid or to prevent allergies. The term fructooligosaccharide or fructopolysaccharide refers to a polysaccharide carbohydrate containing at least 10 β-linked fructose unit chains, wherein the polymeric acid (DP) is 10 to 300, preferably 20 to 300. Inulin is preferred. Inulin is, for example, marketed under the trade name "Raftilin HP". ®Inulin is commercially available (Orafti). As used herein, the term "inulin" refers to glucose-terminated fructose chains in which at least 90% of the fructose units have a DP of 10 to 300. Inulin can be described as GF... n In this formula, G represents a glucose unit, F represents a fructose unit, and n is the number of fructose units linked together, where n is 9 or more. However, due to hydrolysis during processing, a small portion of inulin molecules may not have terminal glucose units. The average DP of the fructose polysaccharide is preferably at least 10, more preferably at least 15, more preferably at least 20 or more, and at most 300. In inulin, fructose units are β(2... 1) Bonding. In the nutritional composition of the present invention, the fiber is selected from fructooligosaccharides, polydextrose and partially hydrolyzed guar gum, preferably containing 0.2 to 8 grams, or even more preferably 0.5 to 5 grams of fructose polysaccharides, based on the dry weight of 100 g of the nutritional composition.

[0025] According to a particularly preferred embodiment, polydextrose is used as fiber to stimulate lactic acid-utilizing bacteria or to prevent allergies. Polydextrose or indigestible polydextrin refers to digestible resistant (maltodextrin) or digestible resistant polydextrose, or indigestible starch, with a DP of 10 to 50, preferably 10 to 20. At least 75% of the polydextrose is indigestible, preferably at least 90%. These polydextroses are preferably prepared by a combination of hydrolysis and transglucosidation. In a preferred embodiment, the polydextrose contains α(1... 4) α (1 6) Glycosidic bonds and 1 2 and 1 3-bond. Polydextrose, for example, is available from Matsutami Inductries under the trade name "Fibersol 2®", from Tate and Lyle under the trade name "Sta-Lite®" Polydextrose, from Ingredion under the trade name "Novelose 330®", or from Danisco under the trade name "Litesse®". In the nutritional composition of the present invention, the fiber is selected from fructooligosaccharides, polydextrose, and partially hydrolyzed guar gum, and preferably contains 0.5 to 8 grams, even more preferably 1 to 5 grams of digestible resistant polydextrose, based on the dry weight of 100 g of the nutritional composition.

[0026] Macronutrients The compositions of the present invention preferably comprise 5 to 16 en% protein, 35 to 60 en% fat, and 25 to 75 en% carbohydrates; more preferably 5 to 12.0 en% protein, 39 to 50 en% fat, and 40 to 55 en% digestible carbohydrates. The term "en%" is an abbreviation for energy percentage and indicates the relative amount of each component's contribution to the total caloric value of the preparation. For example, 40 en% digestible carbohydrates equals 10 g carbohydrates / 100 kcal, since 1 g of carbohydrates has 4 kcal.

[0027] The composition preferably contains 1.4 to 6 g of protein source per 100 ml. This equates to 8.5 to 19 g of protein source per 100 g dry weight. The protein source may include complete protein, hydrolyzed protein, peptides, or free amino acids, or mixtures thereof. Suitable protein sources include milk protein, casein, whey, and soy protein. Protein content is based on Kjeldahl percentage, N... 6.38.

[0028] The composition preferably further contains 2.1 to 6.5 g fat / 100 ml, and comprises 0.3 to 1.5 g linoleic acid (LA) / 100 ml and at least 50 mg α-linolenic acid (ALA) / 100 ml, wherein the LA / ALA ratio ranges from 5 to 15. Based on dry weight, the composition preferably contains 12.5 to 30 g fat, 1.8 to 12.0 g LA, and at least 0.30 g ALA per 100 g, wherein the LA / ALA ratio ranges from 5 to 15. The amount of saturated fatty acids is preferably 10 to 58% by weight of total fatty acids, the concentration of monounsaturated fatty acids is 17 to 60% by weight of total fatty acids, and the concentration of polyunsaturated fatty acids is 11 to 36% by weight of total fatty acids. These amounts and the ALA / LA ratio have the advantage of achieving a balanced biosynthesis of n-3 and n-6 ​​polyunsaturated fatty acids. Preferably, the compositions of the present invention contain long-chain polyunsaturated fatty acids (LC PUFAs), such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA). Suitable lipid sources are milk fat, canola oil, safflower oil, sunflower oil, olive oil, coconut oil, marine bio-oils, etc., or fractions or mixtures of suitable fatty acids.

[0029] The composition of the present invention preferably contains 6 to 19 g of digestible carbohydrates per 100 ml, more preferably 6 to 19 g of lactose.

[0030] Nutritional composition The compositions of the present invention are preferably administered in liquid form. To meet caloric requirements, the composition preferably contains 50 to 200 kcal / 100 ml, more preferably 60 to 90 kcal / 100 ml. Preferably, the composition is in liquid form with a viscosity of less than 35 cps. Where suitable, the composition is in powder form, which can be reconstituted into a liquid with water. Preferably, the nutritional composition of the present invention, or the nutritional composition used in the method or application of the present invention, is a subsequent formulation or an infant formula.

[0031] application Abnormal temporal dynamics regarding the microbiota (preferably lactate-utilizing bacteria) and its metabolites (preferably lactate) have been observed in infants with allergies (particularly eczema) during the first 18 months of life, up to 26 weeks of age. Therefore, these dynamics can be used to assess risk in infants, and they can be designed to be improved to resemble those present in infants without allergies (particularly eczema).

[0032] Therefore, in one embodiment, the present invention relates to a method for assessing whether an infant has an increased risk of developing allergies, the method comprising determining the concentration and / or percentage of lactic acid, based on total organic acids, in fecal material obtained from the infant at approximately 20 to 35 weeks of age, preferably approximately 26 weeks of age, and at an earlier time point, at approximately 3 to 17 weeks of age, preferably approximately 4 to 12 weeks of age, preferably 4 and / or 12 weeks of age. At the time point of 20 to 35 weeks of age, preferably approximately 26 weeks of age, compared to an earlier time point, more preferably 4 and / or 12 weeks of age, when the amount (e.g., concentration) and / or percentage of D-lactic acid, L-lactic acid, or the sum of D-lactic acid and L-lactic acid is higher (e.g., higher than 26 weeks of age), the infant has an increased risk of developing allergies. At the time point of 20 to 35 weeks of age, preferably approximately 26 weeks of age, when the amount of L-lactic acid is greater than 10 mmol / kg of feces, the infant has an increased risk of developing allergies. Compared to earlier time points (around 3 to 17 weeks of age, preferably around 4 to 12 weeks, most preferably 4 weeks and / or 12 weeks of age), infants at 20 to 35 weeks of age, preferably around 26 weeks of age, have an increased risk of developing allergies when the relative levels of D-lactic acid, L-lactic acid, or the sum of D-lactic acid and L-lactic acid are higher. The amount of lactic acid in feces or colon refers to its concentration in feces or colon, for example, mol / kg or mol / L. The relative amount of lactic acid involves the molar percentage of lactic acid based on total organic acids, which is the sum of D-lactic acid and L-lactic acid, acetic acid, propionic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid. Infants at 20 to 35 weeks of age, preferably around 26 weeks of age, when the relative level of L-lactic acid is greater than 10%, have an increased risk of developing allergies.

[0033] Therefore, in one embodiment, the present invention relates to a method for assessing whether an infant has an increased risk of developing allergies, the method comprising determining the amount or relative amount of lactate-utilizing bacteria in fecal material obtained from the infant at about 20 to 35 weeks of age, preferably about 26 weeks of age, and at an earlier time point, at about 3 to 17 weeks of age, preferably about 4 to 12 weeks of age, preferably 4 weeks of age. The lactate-utilizing bacteria are preferably bacteria that utilize lactate to produce butyrate, preferably anaerobic bacteria and / or Eubacterium species. Preferably, fecal anaerobic Corynebacterium, Anaerostipes butyraticus , Anaerostipes hadrus , Anaerostipes rhamnosivorans、E hallii and E. limosum The total amount. When the amount of lactate-utilizing bacteria is lower or slightly increased at a time point of 20 to 35 weeks of age, preferably about 26 weeks of age, compared to earlier time points (approximately 3 to 17 weeks of age, preferably about 4 to 12 weeks of age, most preferably 4 weeks of age), the infant has an increased risk of developing allergies. Bacterial quantity refers to the amount of bacteria per ml of feces. Bacterial quantity can also be expressed as concentration or abundance. Relative quantity and relative abundance refer to the percentage of a specific bacterial group based on the total bacterial count.

[0034] In one embodiment, the present invention relates to a method for preventing or reducing the risk of allergies, said method being carried out by administering a fiber that utilizes lactate-producing bacteria or stimulates lactate-producing bacteria, or both. These fibers and bacteria have been described in detail above. Alternatively, the present invention relates to administering one or more fibers selected from the group consisting of fructooligosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more, said fibers being used to stimulate lactate-producing bacteria in appropriate amounts.

[0035] Allergies are associated with allergic diseases and are symptoms caused by the immune system's allergic reaction to certain substances in the environment, which are usually not bothersome to most people. Allergic diseases include hay fever, food allergies, atopic dermatitis, rhinitis, and allergic asthma. Allergies are particularly identified based on their skin symptoms. In a preferred embodiment, the allergy is eczema. In another preferred embodiment, the eczema includes one or more of allergic eczema, allergic dermatitis, and allergic eczematous dermatitis syndrome (AEDS). Eczema can be diagnosed based on a 2 / 3 positive score according to the modified Hanifin and Rajka criteria (Kunz et al., 1997, Dermatology 195(1):10-19).

[0036] Because the time of lactate accumulation is highly correlated with the time of consumption by lactate-utilizing bacteria, it is preferable to administer the method or nutritional composition of the present invention to infants who are beginning to be introduced into complementary feeding or solid foods. Near weaning, the diversification of an infant's diet not only signifies a gradual diversification into an adult gut microbiota but also exposes the infant to increasing levels of dietary antigens, requiring the immune system to respond adequately to these harmless substances while ensuring defense against potential pathogens. At approximately 6 months of age (e.g., at approximately 26 weeks of age), establishing lactate-utilizing bacteria proves important for establishing and maintaining homeostasis of our immune system during this critical developmental stage. Therefore, in one embodiment of the method or use of the present invention, a nutritional composition is administered to an infant, wherein the infant is in the process of introducing complementary feeding or solid foods.

[0037] Since the time it takes for lactate to accumulate is highly correlated with the time it takes for bacteria that utilize lactate to consume it, it is preferable to administer the method or nutritional composition of the present invention to infants aged approximately 5 to 18 months, more preferably 6 to 12 months. This corresponds to the age at which weaning occurs. Attached Figure Description

[0038] This figure shows the principal response curves, which represent the changes in bacterial metabolites (i.e., the levels of short-chain fatty acids (SCFAs) and lactic acid) over time and their interaction with eczema.

[0039] Example 1: Abnormal temporal dynamics in infants with eczema in the first 18 months of life; in infants with eczema In infants, the microbial conversion rate of lactic acid is reduced. Stool samples were collected from infants at 4, 12, and 26 weeks of age. Stool samples were collected by parents in 10 ml stool containers (Greiner Bio-One, Kremsmunster, Austria), immediately frozen (-12°C to -20°C), and delivered to the hospital within three months in cryogenic storage bags with ice packs. Upon arrival at the hospital and before laboratory evaluation, samples were stored at ultra-low temperatures (-75°C to -85°C) and transported. Frozen stool samples were thawed on ice and diluted 10-fold in PBS buffer (150 mM NaCl, 10 mM Na2HPO4, 20 mM NaH2PO4, pH 7.4), and homogenized by adding 5 to 10 glass beads (3 mm in diameter) and vortexing for 3 min. Glass beads and larger particles were removed by centrifugation at 300 × g for 1 min. Several 1 ml aliquots of the homogenized suspension were stored at ultra-low temperatures until further processing and analysis.

[0040] The fecal suspension was thawed on ice and centrifuged at 14,000 × g for 10 min. Then, 350 μl of the supernatant was heated at 100 °C for 10 min to inactivate all enzymes and centrifuged again. A portion of the supernatant was used for the quantitative determination of SCFA acetic acid, propionic acid, butyric acid, isobutyric acid, isovaleric acid, and valeric acid by gas chromatography. Another portion of the supernatant was used for enzymatic analysis of lactate levels using a D- / L-lactic acid assay kit (Megazyme, Wicklow, Ireland).

[0041] 16S rRNA gene sequencing was used to characterize the microbiome composition of feces collected at 4 and 26 weeks of age from a group of vaginally delivered infants, including breastfed infants (BF, n = 30) and infants receiving either experimental or control formula (n = 51) or control formula (n = 57). Eczema was diagnosed at 18 months of age based on a positive score of 2 / 3 according to the modified Hanifin and Rajka criteria (Kunz et al., 1997, Dermatology 195(1): 10–19). Of these 138 infants, 52 had eczema at 18 months of age. Fecal samples for microbial analysis were selected according to the following criteria: (I) infants selected from the breastfed reference group and the target critical group (KGI), which consisted of those who started formula before 4 weeks of age; (II) vaginally delivered infants; and (III) fecal specimens were available at 4, 12, and 26 weeks of age.

[0042] The fecal suspensions were thawed on ice, and 200 µl of each suspension was mixed with 450 µl of extraction buffer (100 mM Tris-HCl, 40 mM EDTA, pH 9.0) and 50 µl of 10% sodium dodecyl sulfate. Bead-beating phenol-chloroform extraction was then performed as described by Matsuki et al., 2004, Appl Environ Microbiol 70:167-173, except that the DNA was resuspended in 0.1 mL TE (10 mM Tris-HCl, 1 mM EDTA, pH 8.0). The V3-V5 region of the 16S rRNA gene was amplified using the forward primer 357F and the 'Bifidobacterium-optimized' reverse primer 926Rb. The reverse primer included a 12-base-pair error-corrected Golay barcode. As previously described (Sim et al., 2012, PLoSOne 7: e32543), PCR was performed in quadruplicate. The replication amplicon was pooled and purified, and pyrosequencing was performed three times using a 454 Life Sciences GS FLX (Roche, Branford, CT, USA) according to the Roche AmpliconLib-L protocol.

[0043] The "Quantitative Insights Into Microbial Ecology" (QIIME) v1.5.0 package was used to analyze shotgun-processed data (Caporaso et al., 2010, Nat Methods 7: 335-336). First, AmpliconNoise was used to denoise the sequencing data, followed by Perseus to remove chimeras (Quince et al., 2011, BMC Bioinformatics 12: 38). Alignment with the SILVA rRNA database (SSU_REF108) (Pruesse et al., 2007 Nucleic Acids Res 35: 7188-7196) was performed for reference, and the UCLUST algorithm (Edgar, 2010 Bioinformatics 26: 2460-2461) was used to cluster sequences with 97% sequence identity as the operational unit (OTU). Sparsity was then applied, and sequences appearing only once in the dataset (single sequences) were removed.

[0044] Statistical analyses of 16S rRNA gene markers (OTU frequencies) and bacterial metabolite data (SCFA and lactate levels) were performed using Canoco 5 software (Šmilauer and Lepš., 2014, Multivariate Analysis of Ecological Data using CANOCO 5, 2nd Edition, edn. Cambridge University Press: Cambridge Books Online); and differential abundance tests were performed using R-package MetagenomeSeq (Paulson et al., 2013, NatMeth 10: 1200-1202). OTU count data were first clustered at the genus level, yielding a total of 142 genera, which were then normalized by summation scaling and logarithmic transformation. Genera present in fewer than 10 samples were discarded to account for data sparsity. This resulted in 58 taxonomic features, which were used as input for the statistical analyses. Using constrained ordination and Monte Carlo permutation tests (MCPT), Canoco 5 was used to model categorical data to assess the explanatory power of sample covariates (Ter Braak, 1986, Ecology 67: 1167-1179; Van den Brink and Ter Braak, 1999, Environmental Toxicology and Chemistry 18: 138-148), with a significance of 0.05. Subsequently, the identified sample covariates were used in all models and comparisons. The Benjamini-Hochberg false discovery rate (FDR) was used to explain multiple comparisons (Benjamini and Hochberg, 1995 Journal of the Royal Statistical Society Series B (Methodological) 57: 289-300), with an adjusted p-value (P-adj) significance of 0.05.

[0045] The constrained ordination method was combined with forward selection of variables from Canoco 5 to identify sample covariates that explain most of the variation in microbial taxonomic composition (Legendre and Legendre, 2012 Numerical ecology, Vol. 24. Elsevier: Amsterdam; Ter Braak, 1986). The forward selection method identified age (in weeks), feeding group (formula 1, 2, or a reference group for breastfeeding), ethnicity (Asian, Caucasian, or others), and siblings (yes or no) as significantly influencing bacterial taxonomic composition in fecal samples (using the Benjamini-Hochberg method to control for false discovery rate, significance 0.05). Subsequently, the identified sample covariates were used in all models and comparisons, as explanatory variables or as covariates, with a adjusted p-value (P-adj) significance of 0.05.

[0046] The effects of eczema on bacterial metabolites (SCFA and lactate) over time were assessed using the primary response curve (PRC) and the Monte Carlo permutation test (MCPT, with 499 permutations and a significance level of 0.05) (Van den Brink and TerBraak, 1999). Differential abundance of bacterial genera was assessed using MetagenomeSeq with the Benjamini Hochberg false discovery rate, with a significance level of 0.05.

[0047] Univariate data analysis was performed using the GraphPad Prism version 6.02 window (GraphPad Software, La Jolla, California, USA). The Mann-Whitney test was applied for comparisons between two groups, and the Kruskall-Wallis and Dunn's multiple comparison tests were applied for comparisons between three or more groups, with a significance level of 0.05.

[0048] result Table 1 shows the amount of fecal lactate at different time points. At weeks 4 and 12, lactate levels tended to be lower in infants with eczema, but the difference was not statistically significant. However, at week 26, D-lactic acid and L-lactic acid levels were significantly higher in infants with eczema. Similar results were observed when lactate was expressed as a percentage of total organic acids (the sum of D-lactic acid, L-lactic acid, acetic acid, butyric acid, propionic acid, valerate, isobutyric acid, and isovaleric acid), see Table 2.

[0049] The effect of eczema on fecal bacterial metabolite composition over time was investigated using the primary response curve (PRC, Van den Brink and Ter Beek, 1999), while adjusting for all identified significant covariates. Significant temporal differences were observed on the first constraint axis due to interactions. The kinetics of these differences were most pronounced between 12 and 26 weeks of age. Infants with eczema were characterized by decreased levels of both lactate isomers at 12 weeks of age, a pattern that subsequently reversed at 26 weeks of age. In this plot, the horizontal axis represents time, and the vertical axis represents the PRC score. Infants without eczema (NO ECZEMA; dashed line ------) were used as the reference level, and their PRC value was zero, so their curve lies above the horizontal axis. The changes in infants with eczema during the first 18 months of life (ECZEMA; solid line --) are shown as the response curve relative to this reference. Microbial response scores are shown on a separate vertical (one-dimensional) plot. Multiplying the PRC score by the response score provides a quantitative explanation of the direction of microbial changes in infants with eczema at each time point (weeks 4, 12, and 26) compared to those without eczema. For the first PRC, the results of the PRC analysis of fecal SCFA and LA are shown, indicating that the interaction was significant (MCPT: P = 0.034, explaining 84.4% of the variance, 499 permutations).

[0050] Table 1: D-lactic acid and L-lactic acid, in mmol / kg wet weight feces n = number of non-missing subjects, Q1 = 25th quartile and Q3 = 75th quartile. Statistical summaries were based on the Kruskall-Wallis and Dunn multiple comparison test, which compared age-matched infants with eczema to those without eczema (ns = P > 0.05). = P≤0.05, = P≤0.01) The effect of eczema on fecal bacterial metabolite composition over time was investigated using the primary response curve (PRC, Van den Brink and Ter Beek, 1999), while adjusting for all identified significant covariates. Significant temporal differences were observed on the first constraint axis due to interactions. The kinetics of these differences were most pronounced between 12 and 26 weeks of age. A symptom of eczema in infants was a decrease in the levels of both lactate isomers at 12 weeks of age, a pattern that subsequently reversed at 26 weeks of age. In this plot, the horizontal axis represents time, and the vertical axis represents the PRC score. Infants without eczema (no eczema; dashed line ------) were used as the reference level, and their PRC value was zero, so their curve lies above the horizontal axis. The changes in infants with eczema during the first 18 months of life (with eczema; solid line --) are shown as response curves relative to this reference. Microbial response scores are shown on a separate vertical (one-dimensional) plot. Multiplying the PRC score by the response score provides a quantitative explanation of the direction of microbial changes in infants with eczema at each time point (weeks 4, 12, and 26) compared to those without eczema. For the first group of PRCs, the results of the PRC analysis of fecal SCFA and LA are shown, indicating that the interaction was significant (MCPT: P = 0.034, explaining 84.4% of the variance, 499 permutations).

[0051] Table 2: Relative abundance of D-lactic acid and L-lactic acid, expressed as mol% of total organic acids. n = number of non-missing subjects, Q1 = first quartile and Q3 = third quartile. Statistical summaries were based on the Kruskall-Wallis and Dunn multiple comparison test, which compared age-matched infants with eczema to those without (ns = P > 0.05). = P≤0.05, = P≤0.01) Therefore, at 26 weeks of age, infants who had eczema within the past 18 months had higher levels and percentages of lactic acid in their stool compared to infants who did not have eczema within the past 18 months, and these levels and percentages were also increased compared to earlier time points of week 4 and week 12. On the other hand, in infants who did not have eczema, fecal lactate levels were lower at 26 weeks compared to earlier time points.

[0052] Table 3: Relative abundance (%) of Eubacterium species n = number of non-missing subjects; statistical summaries were based on the Kruskall-Wallis and Dunn multiple comparison test, which compared infants of the same age with eczema to those without eczema (ns = P>0.05). = P≤0.05, = P≤0.01) Table 4: Relative abundance (%) of anaerobic bacterial genera. n = number of non-missing subjects; statistical summaries were based on the Kruskall-Wallis and Dunn multiple comparison test, which compared infants of the same age with eczema to those without eczema (ns = P>0.05). = P≤0.05, = P≤0.01) MetagenomeSeq was used to assess the differential abundance of bacterial taxa over time in infants with and without eczema, and to evaluate the differences in taxa over time by comparing the two groups, while adjusting for identified covariates. Compared to infants with eczema, a more pronounced increase in *Eubacterium* and *Anaerobes* species over time was observed in infants without eczema (see Tables 3 and 4). These two genera are associated with a specific microbiome known to primarily convert lactate, along with acetate, into butyrate, and are therefore termed lactate-utilizing bacteria (LUB). Lactate levels were indeed negatively correlated with the presence of lactate-utilizing bacteria.

[0053] In the early life, between weeks 4 and 12, before weaning begins, increased levels of acetate and lactate, and decreased levels of propionate and butyrate, are crucial for establishing LUBs such as Eubacterium and anaerobic bacteria by around 6 months of age, as observed in this study, with infants without eczema subsequently outperforming those with eczema.

[0054] In summary, this study is the first to demonstrate a link between microbiome function and the expression of allergic phenotypes in early life. It highlights the importance of early life microbial species succession and metabolite crossfeeding for the development of gut physiology supporting gut development and for the development of normal environmentally triggered immune responses. These observations could contribute to the formulation of optimal nutritional strategies to support the timely gut clustering of key species in an increasingly diverse infant gut.

[0055] Example 2: L-lactate accumulation in the feces of infants with allergies To gain a deeper understanding of the development of the gut microbiota in initially healthy infants with allergies in early life, and to identify reasonable microbiome biomarkers for allergic diseases, a nested case-control study was conducted on a large cohort of Chinese infants born in Singapore. Using 16S rRNA sequencing, gut microbiota maturation and metabolism were measured in 20 paired allergic cases and non-allergic controls during the first 6 months of life. Allergic infants were assessed by the cumulative incidence of clinical allergic symptoms (eczema flare-ups / allergic rhinitis / food allergies) and SCORAD scores; according to this study, the eczema workflow was up to 12 months of age. Infants with allergies at 12 months of age had significantly higher fecal L-lactate levels (12.25 mmol / kg wet weight stool) at 6 months of age compared to non-allergic infants (3.95 mmol / kg wet weight stool), P < 0.05. In the allergic infant group, L-lactate levels were higher at 6 months compared to week 3 and month 3, indicating lactate accumulation in this group. The opposite is true for non-allergic infants; the amount of L-lactic acid in their stool is higher in the 3rd week and 3rd month.

[0056] Table 5: L-lactic acid, in mmol / kg wet fecal weight Example 3: Selective fiber to stimulate lactate-utilizing bacteria Fresh fecal samples were collected from four healthy adults, pooled, and aliquoted into smaller portions mixed with 10% glycerol in an anaerobic chamber and stored at -80°C. Prior to the experiment, the fecal samples were thawed and mixed with fermentation medium at a 1:5 ratio in Falcon tubes. At t = 0, 6 ml of this suspension was added to a Falcon tube containing the target substrate and mixed. The mixed suspension was placed in a dialysis tube, which was then placed in a 100 ml bottle containing 100 ml of dialysis medium. The bottle was closed and incubated at 37°C. Fermentation without added carbohydrates was used as a negative control (blanc), while fermentation using glucose was used as a positive control. Fiber and glucose were added at a concentration of 200 mg / 6 ml fecal suspension.

[0057] Nineteen single fibers and three fiber mixtures were tested. Fermentation was carried out under anaerobic conditions at 37°C for 48 h. The initial pH of the buffer solution was 6.3.

[0058] Preservative medium: 20.0 g / L buffered peptone, 0.5 g / L L-cysteine-HCl, 0.5 g / L sodium thioglycolate, 1 resazurine tablet / L, adjusted to pH 6.7 ± 0.1 with 1 M NaOH or HCl. Boil in a microwave oven. Transfer 25 ml of the medium to a 30 ml serum bottle. Sterilize at 121°C for 15 minutes.

[0059] McBain & MacFarlane medium: 3.0 g / L buffered peptone water, 2.5 g / L yeast extract, 0.8 g / L mucin (brush-like edge), 3.0 g / L tryptone, 0.4 g / L L-cysteine-HCl, 0.05 g / L bile salts, 2.6 g / L K₂HPO₄·3H₂O, 0.2 g / L NaHCO₃, 4.5 g / L NaCl, 0.5 g / L MgSO₄·7H₂O, 0.228 g / L CaCl₂, 0.005 g / L FeSO₄·7H₂O. Pour the medium into 500 ml Scott flasks and sterilize at 121°C for 15 minutes.

[0060] Buffer medium: K₂HPO₄·3H₂O 2.6 g / L, NaHCO₃ 0.2 g / L, NaCl 4.5 g / L, MgSO₄·7H₂O 0.5 g / L, CaCl₂ 0.228 g / L, FeSO₄·7H₂O 0.005 g / L. Adjust the pH to 6.3 ± 0.1 with K₂HPO₄ or NaHCO₃. Pour the culture medium into 500 ml Scott flasks and sterilize at 121°C for 15 minutes.

[0061] Fecal suspension: Centrifuge the preserved fecal solution at 13,000 rpm for 15 minutes. Remove the supernatant and mix the feces with McBain & Mac Farlane medium at a weight ratio of 1:5.

[0062] Fecal samples were stored in RNAlater solution (Ambion, Courtaboe, France) for subsequent bacterial DNA or RNA isolation. The fecal samples were homogenized, and the RNAlater volume was adjusted to obtain a final 1:10 fecal solution. 200 µl of this 10-fold dilution was added to 1 ml of PBS buffer and centrifuged at 5000 g for 5 min. The supernatant was discarded, and the pellet was stored at -80°C. Fecal DNA and RNA were extracted. Bacterial abundance was determined based on RNA molecule quantification using primers primarily targeting the 16S rRNA sequence. To ensure a common scale of comparison with other bacterial quantification methods, the number of molecules detected (RNA or DNA) was given in cell equivalents (CE), with a bacterial culture of a reference strain used as a standard curve.

[0063] To determine the target bacteria present in fecal samples, three consecutive 10-fold dilutions of extracted RNA or DNA samples were applied to qPCR or RT-qPCR, and the CT values ​​within the linear range of the tests were plotted against a standard curve generated in the same experiment to obtain the corresponding bacterial counts for each nucleic acid sample, which were then converted to per-sample counts. Different bacterial species were analyzed, including one lactate-utilizing bacterium, *Corynebacterium fecalithum*. Statistical analysis was performed using the Mann-Whitney method.

[0064] result At t = 0, the amount of fecal anaerobic corynebacteria is equivalent to 2 10 8 cfu / ml. After fermentation with glucose for 48 h, the amount was doubled to 4. 10 8 cfu / ml.

[0065] Of the 19 different fibers and 3 fiber mixtures tested, the following fibers were observed to significantly increase fecal anaerobic corynebacteria compared to the control at T = 48 h (glucose): Orafti ® GR (Beneo), inulin with DP > 10 (5x), Orafti ® HP (Beneo), long-chain inulin with average DP > 23 (5x), Benefiber ® (Novartis) Partially Hydrolyzed Guar Gum (PHGG) (4x), Sta-Lite ® (Tate and Lyle) Polydextrose with DP > 10 (5 times) and Novelose ®330 (national starch) is a resistant starch (3 times stronger). A fiber mixture rich in inulin also stimulates the growth of fecal anaerobic bacteria.

[0066] Compared to the glucose control, other fibers tested, such as short-chain FOS Actilight, were observed to be more effective. ® (Meiji) and Frutalose ® (Orafti) (both with average DP <5), showed no increase or even decrease. Table 6 shows the positive results for fructooligosaccharides with an average DP of 10 or higher, polydextrose with an average DP of 10 or higher, and partially hydrolyzed guar gum with an average DP of 10 or higher. For comparison, results for non-positive short-chain fructooligosaccharides are included.

[0067] Table 6: Increase in fecal anaerobic Corynebacterium after fermentation of several types of fibers.

Claims

1. A nutritional composition comprising lactate-utilizing bacteria and at least one fiber, said fiber being selected from: fructooligosaccharides with an average DP of 10 or more, polydextrose with an average DP of 10 or more, and partially hydrolyzed guar gum with an average DP of 10 or more, wherein the lactate-utilizing bacteria are selected from the genus Anaerobic bacteria (…). Anaerostipes ) and Eubacterium ( Eubacterium ).

2. The nutritional composition according to claim 1, wherein the amount of bacteria utilizing lactate is 10. 2 Up to 10 9 cfu / g dry weight.

3. The nutritional composition according to claim 1 or 2, wherein the amount of fiber is 0.2 to 8 g / 100 g dry weight.

4. The nutritional composition according to claim 1 or 2, wherein it is a subsequent formulation or an infant formula.

5. Use of the nutritional composition according to any one of claims 1-4 for the prevention of allergies or for reducing the risk of developing allergies.

6. The use according to claim 5, wherein the nutritional composition is intended for use in infants or young children.

7. The use according to claim 5, wherein the allergy is eczema.

8. The use according to claim 5, wherein the nutritional composition is a follow-up formulation or an infant formula.

9. The use according to claim 5, wherein the nutritional composition is given to an infant, and wherein the infant is an infant in the process of introducing supplemental feeding or solid food.

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