INFANT NUTRITIONAL COMPOSITION FOR USE IN IMPROVING PANCREATIC MATURATION AND INSULIN BIOSYNTHESIS.

Abstract

This invention relates to nutritional compositions comprising at least one fucosylated oligosaccharide, preferably 2FL, for use in enhancing pancreatic development and / or pancreatic maturation in infants, and / or improving insulin biosynthesis, and / or preventing metabolic disorders or associated diseases, and / or managing glucose during nutritional intervention or later in life. The composition may be an infant formula. The composition may also comprise at least one N-acetylated oligosaccharide, preferably LnNT.

Description

The present invention relates to a nutritional composition comprising at least one human milk oligosaccharide (HMO) for use in enhancing pancreatic development and / or pancreatic maturation in infants. The invention also relates to improving glucose management and, ultimately, to aiding in the prevention and / or improvement of related health disorders (such as obesity or type 2 diabetes) in infants, young children, or individuals later in life. BACKGROUND OF THE INVENTION Optimal development of functional organs is of paramount importance for all infants, and especially for those at risk because their overall development is affected by genetic factors, external factors, infections, metabolic disorders, diseases, or suboptimal health conditions. This development obviously begins in utero but continues after birth. Therefore, the infant's nutritional status is critically important both in utero (as it can be influenced by the mother's health, which affects nutrient delivery through the umbilical cord) and after birth. In the first days / months, nutritional status depends on the nutrients provided (breast milk, infant formula) but also on the The infant's ability to ingest (sucking ability), digest (gastrointestinal functions), absorb, and utilize nutrients is essential. The pancreas produces several enzymes that are secreted into the small intestine, where they contribute to digestive functions. The pancreas also produces several hormones, notably insulin, which is secreted into the bloodstream, where it regulates the body's glucose or sugar level. As such, the pancreas participates in at least two extremely important metabolic functions: intestinal digestion and glucose management. Dysregulation of one or both of these functions directly affects an individual's health, both at the time of the dysfunction and later in life. For example, malabsorption of nutrients by the intestine can induce growth retardation, poor neurological development, and also affect immune defenses in the short term and later in life.The low insulin biosynthesis produced by the pancreas can induce high levels of circulating glucose and reduced glucose availability in vital organs such as the brain and muscles immediately, but also metabolic disorders such as diabetes and overweight / obesity later in life. Pancreatic development begins in utero but continues throughout infancy, childhood, and adulthood.As explained by Susan Bonner-Weir et al (Dynamic development of the pancreas from birth to adulthood; Ups J Med Sci 2016 May; 20 121(2):155-158, PMID:260Q88'6), after birth the endocrine pancreas continues its development, a complex process involving both the maturation of islet cells and a marked expansion of their numbers. New beta cells are formed both by duplication of pre-existing cells and by new differentiation (neogenesis) through the first few postnatal weeks, resulting in 25 beta cells of different stages of maturation even after weaning. Consequently, there is a need to ensure optimal pancreatic development and maturation in all infants over a long period. More specifically, there is a need to ensure optimal pancreatic development and maturation for infants who are particularly at risk, such as preterm infants (i.e., those who have not completed their expected pancreatic development in utero), frail infants (small for gestational age, low birth weight, very low or extremely low birth weight), infants suffering from poor health, infections, or diseases, infants with a particular genetic predisposition, or infants born to a mother who did not ensure optimal development in utero due to her own poor health. It is known that the biosynthesis (production) of insulin and the secretion of insulin by the pancreas are affected by several factors, such as genetic factors, plasma glucose levels, or some peptides such as ghrelin (see “Ghrelin, A New Gastrointestinal Endocrine Peptide that Stimulates Insulin Secretion”). Enteric Distribution, Ontogeny, Influence of Endocrine, and Dietary Manipulations”, Heung-Man Lee Guiyun Wang Ella et al, Endocrinology, 43-1, pages 185-190; 1-12012). The biosynthesis and secretion of insulin by the pancreas can also be influenced directly or indirectly by the subject's nutrition (e.g., sugar intake), but these aspects are much less known. In particular, it has been described that insulin secretion is influenced by the nutritional composition containing di- or oligosaccharides (EP1332759A; Kyowa Hakko Kogyo Go. LTD, published 6.8.2003), while the effect on the biosynthesis / production of insulin by the pancreatic cell islets is not described. 5 In fact, insulin secretion by pancreatic β cells and the ability of pancreatic islets to produce insulin are regulated by two different pathways. Insulin biosynthesis is regulated by glucose and other nutrient levels as well as by receptors at both transcriptional and translational levels. Insulin secretion is primarily regulated by glucose levels and is modulated by other nutrients and hormonal signals. Insulin secretion is generated by cell signaling transduction pathways as well as by the fusion / transport / acquisition of insulin granules (Regulation of Insulin Synthesis and Secretion and Pancreatic Beta-Cell Dysfunction in Diabetes, Zhuo Fu, E, R Gífbert and Dongmto Lui, Curr. Diabetes Rev 2013, Jan 1; 9(1):25-53).Some of the effectors that act on insulin secretion from the pancreas may, in fact, be different from those that act on insulin biosynthesis by pancreatic cells. These effectors may act through mechanisms different from those involved in insulin biosynthesis by pancreatic cells. Similarly, enhancing insulin biosynthesis by the pancreatic islets may or may not increase secretion, as the pancreas also acts as a receptacle for insulin.However, beyond theory, it is thought that improvements in insulin biosynthesis affect the ability to secrete insulin into the bloodstream over time during the 20-25 year life cycle. Conversely, secretion mechanisms primarily deal with the short-term ability to increase blood insulin concentrations until the pancreatic storage capacity is exhausted. Simply put, they empty the reservoir but do not allow for its replenishment. Because they are mechanically different pathways, an effector in secretion is not necessarily an effector in insulin biosynthesis by pancreatic cells. Consequently, it is important to promote pancreatic development and / or maturation in the first few days, preferably in a way that is non-invasive (to other metabolic pathways), gentle, and does not induce or minimize secondary effects. Beyond theory, it is thought that promoting pancreatic development and / or maturation can interact at least at three levels: increasing the number of pancreatic β cells, maturing individual cells, and / or increasing the amount of insulin synthesis per cell. All three pathways have the potential to induce the desired overall increase in insulin secretion and, therefore, also have a long-term influence on glucose management in individuals. In this context, nutritional interventions are a tool of choice for optimizing health conditions. There is a need to identify and make use of specially targeted nutritional ingredients or nutritional compositions to induce improved or optimal development or maturation of the pancreas and / or pancreatic function. There is a need to provide such an effect at the earliest possible stage of childhood and, preferably, to observe the benefits of such nutritional intervention also later in life. There is a need to increase insulin biosynthesis by pancreatic islets in infants and to improve insulin biosynthesis levels. There is a need to influence glucose management at the time of nutritional intervention and later in life and to reduce the risk, prevent and / or treat associated metabolic disorders such as diabetes (type 2), obesity or overweight. There is a particular need to induce these beneficial effects in 25 infants affected or at risk of being affected® by development or maturation Suboptimal pancreatic 2Q, There is a particular need to induce these beneficial effects in frail, premature, low birth weight, very or extremely low birth weight infants or infants who have a particular risk (including genetic risk) of poor pancreatic maturation or predisposition to be affected by suboptimal glucose management (or associated diseases). There is a need to deliver such beneficial health effects in a way that does not disrupt other metabolic or developmental pathways and / or induce unwanted side effects. There is a need to deliver such health benefits through whole nutrition in a way that can withstand passage through the gastrointestinal tract! There is a need to bring the pancreatic development and / or maturation and / or related pancreatic insulin biosynthesis level of infants back to the normal zone whenever they deviate from normal development. Breast milk and breastfeeding are best and recommended for all infants. However, in some cases, breastfeeding is unsuitable or unsuccessful for medical reasons, or the mother chooses not to breastfeed. Infant formulas were developed for these situations. Fortifiers were also developed to enrich breast milk or infant formula with specific ingredients. There is clearly a need to develop nutritional compositions for use in improving pancreatic development and / or maturation and / or in increasing / improving the level of biosynthesis / production of insulin by the pancreas. Furthermore, there is a need to provide such health benefits to There is a need to provide health benefits to infants and young children in a way that is particularly appropriate, such that it does not involve conventional pharmaceutical intervention, as these infants and young children are particularly vulnerable. There is a need to provide these health benefits in a way that does not induce side effects and / or is easy to deliver and well-accepted by parents or healthcare professionals. Furthermore, there is a need to provide these benefits in a way that keeps the cost of such provision reasonable and affordable for the majority.There is a need to deliver the benefits and target compositions in a way that is convenient to use and to which subjects readily adhere. BRIEF DESCRIPTION OF THE INVENTION The present inventors have discovered that nutrient compositions comprising at least one fucosylated oligosaccharide (preferably 2FL) can be advantageously used to promote and / or enhance the development and / or maturation of the pancreas in infants. In one aspect, the composition of the invention promotes / increases / enhances the pancreatic biosynthesis / production of insulin by pancreatic cells. In one aspect, the composition is an infant formula, a supplement, or a human milk fortifier, and is particularly beneficial for frail or premature infants. In one aspect, the composition of the invention also comprises other oligosaccharides, such as LnNT.In one aspect, the invention relates to the use of a tai composition for use in the induction or promotion of the development or maturation of the pancreas, possibly accompanied by the improvement of insulin biosynthesis. BRIEF DESCRIPTION OF THE FIGURES Figure 1 represents the concentration of insulin in the pancreas of rats 5 on postnatal day 57, in various groups; • IUGR rats: IUGR (intrauterine growth restricted) rats; tube-fed with 3 g / kg / BW of maltodextrin from dZ to d21 and fed a control diet from d22 to d57. • IUGR / 2FL rats: IUGR rats tube-fed 3 g / kg / BW of 2FL from d7 to d21 and fed a supplemental diet containing 0.5% by weight of human milk oligosaccharide 2FL from d22 to d57, • IUGR / LNnT rats: IUGR rats tube-fed 3 g / kg / BW of LNnT from d7 to d21 and fed a supplemental diet containing 4.5% by weight of human milk oligosaccharide LNnT from d22 to d57. · IUGR rats / HMO mix: IUGR rats tube-fed g / kg / BW of HMO mix from d7 to d2T and fed a diet supplemented with 4.5% by weight of human milk oligosaccharides (2FL+LNnT in a 2:1 weight ratio) from d22 to d5Z. The indication (*) means *P< 0.05 DETAILED DESCRIPTION OF THE INVENTION Definitions: As used in the present description, the following terms have the following 25 meanings. The term “infant” means a child under 12 months of age. The expression “toddler” means a child between one and three years of age, also referred to as a child who is beginning to walk. The expression “child” means a child between three and seven years of age. A 'cesarean-born infant or toddler' means an infant or toddler who was born by cesarean section. It means that the infant or toddler was not born vaginally. 'A vaginally born infant or young child' means an infant or young child who was born vaginally and not by cesarean section. A "preterm" or premature infant is a young child who was not born at term. Generally, it refers to an infant or young child born before 37 weeks of gestation. A "low birth weight" infant is a newborn whose body weight is below 2500 g (5.5 lbs), whether due to premature birth or restricted fetal growth. Therefore, this includes: Infant or young child who has / had a birth weight of 1500 to 2500 g (usually called "low birth weight" or LBW) 1000 to 1500 g (called “very low birth weight” or VL8W) infant or young child who has / had a body weight at birth below 1000 g (called “extremely low birth weight” or ELBW). A “small for gestational age (SGA) infant” means a baby with birth weights below the 10th percentile for babies of the same gestational age. The expression "human composition" means a composition that nourishes the subject. Usually, this nutritional composition is administered orally. In some cases, it may be administered intravenously. It usually includes a source of lipid or fat and a source of protein. The nutritional composition is intended for administration to subjects. The nutritional composition of the invention is man-made; that is, it can be formulated, for example, by humans from ingredients (compounds of natural, biological, or chemical origin) or it can be derived, for example, from biological fluids but can be processed through human intervention. The nutritional composition of the invention is not human breast milk. In one particular embodiment, the nutritional composition of the present invention is a “synthetic nutritional composition.” The term “synthetic nutritional composition” means a mixture obtained by chemical and / or biological means, which may be chemically similar or identical to the naturally occurring mixture in mammalian milks (i.e., the synthetic composition is not breast milk). In one particular embodiment, the composition of the present invention is a hypoallergenic nutritional composition. The expression “hypoallergenic nutritional composition” means a nutritional composition that is unlikely to cause allergic reactions. The term “infant formula”, as used in the present description, refers to a food that has a particular nutritional use in infants during the first months of life and that in itself satisfies the nutritional requirements of this category of persons (Article 2(c) of the European Commission Directive) 91 / 321 / EEC 2W141 / EC of 22 December 2006 on infant formulas and follow-on formulas). It also refers to a nutritional composition intended for infants and as defined in the Codex Alimentarius (Codex STAN 72-1981) and Infant Specialties (inc. Food for special medical purposes). The term “infant formula” includes both infant starter formula and follow-on or maintenance formula. A maintenance or 'follow-up' formula is supplied from the sixth month onwards. This constitutes the main liquid element in the progressively diversified diet of this category of people. The expression “baby food” means a food intended for particular nutritional uses by infants or young children during the first years of life. The expression 'infant cereal composition' means a food intended for particular nutritional uses by infants or young children during the first 15 years of life. The term “growing-up milk” (or GIM) refers to a milk-based beverage, usually with added vitamins and minerals, intended for young children, from one year of age and usually up to the third year of age, or children up to seven years of age. The term fortifier refers to liquid or solid nutritional compositions suitable for mixing with breast milk or infant formula. The expression “weaning period” means the period during which breast milk is replaced by another food in the diet of an infant or young child. The expressions 'days / weeks / months / years of life and 25 days / weeks / months / years of birth' can be used interchangeably. § 15 “Maternal milk” should be understood as the mother’s breast milk or milk supply. An “oligosaccharide” is a sugar polymer containing a small number (typically three to ten) of simple sugars (monosaccharides). The term “HMO” refers to oligosaccharide(s) in human milk. These carbohydrates are highly resistant to enzymatic hydrolysis, indicating that they can exhibit essential functions not directly related to their caloric value. It has been particularly illustrated that they play a vital role in the early development of infants and young children, such as the maturation of the immune system. Many different types of HMOs are found in human milk. Each individual oligosaccharide is based on a combination of glucose, galactose, and sialic acid (N-acetylneuraminic acid).ideose and / or N-acetylglucosamine with many and varied linkages between them, which generates the enormous number of different oligosaccharides in human milk: more than 130 such structures have been identified to date. Almost all of these have a lactose entity at their reducing end, while sialic acid and / or fucose (when present) occupy terminal positions at the non-reducing ends. HMOs can be acidic (e.g., charged oligosaccharide containing sialic acid) or neutral (e.g., fucosylated oligosaccharide). A “fucosylated oligosaccharide” is an oligosaccharide that has a fucose residue. It has a neutral nature. Some examples are 2-FL (2'-fucosyllactose), 3FL (3-fucosyllactose), fucosyllactose, lacto-N-tucopentaose (e.g., fucosylated oligosaccharide)., lacto-N-fucopentaose i, lacto-N-fucopenthe II, lacto-N-fucopentaose III, lacto-N-fucopentaose V), lacto-N-fucohexaose, lacto~N~difucohexaose 1, fucosyl-lacto-N-hexaose, fucosIMacto-N* neohexaose, difucosiMacto-N-hexaose 1, difucosiMacto-N-neohexaose II and any 25 combination of these, Without wishing to be subject to the theory, it is requested that the epitopp. Fucosyl-S-fucosilated oligosaccharides can act as a decoy on the mucosal surface. Through a competitive effect, the action of pathogens responsible for infections (of viral or bacterial origin) or their secreted components (e.g., toxins) can be prevented and / or limited, especially by preventing their binding to natural ligands. While not intended to be subject to theoretical constraints, it is believed that this reduces the risk of infections / inflammations, and particularly the risk of infections and / or inflammations of the trichoide. Furthermore, fucosilated oligosaccharides are thought to increase the growth and metabolic activity of specific commensal microbes, reducing the inflammatory response and creating an unfavorable environment for pathogens, thus leading to resistance in colonization.The expressions 'fucosylated oligosaccharides comprising a 2'-fucosyl epitope' and '2'-fucosylated oligosaccharides' encompass fucosylated oligosaccharides with a certain homology of form since they contain a 2'-fucosyl epitope; therefore, a certain homology of function can be expected. Without wishing to be subject to the theory, it is believed that the 2-fucosyl epitope of these fucosylated oligosaccharides is particularly specific to the pathogens (or their secreted components) involved in infections of the TRI and / or ear. The terms 2FL, 2'FL, 2-FL, 2-FL, 2-Fl, 2-fucosyl lactose, and 2-Mucosyl lactose are used interchangeably with the same meaning. The expression 'N-acetylated oligosaccharide(s)' encompasses both the “N-acetyl-20 2S lactosamine as the 'toligosaccharide(s) containing N-acetyl-lactosamine, These are neutral oligosaccharides that have an N-acetyl-lactosamine residue.Suitable examples are LNT (lacto^N-tetraose), para-lacto-N-neohexaose (para-LNnH), LNnT (tacto-N-neotetraose), disialÍllacto-N-tetraose (DSLNT) and any combination of these. Other examples are lacta-N-hexaose (lacto-N-neohexaose, paract^N-hexaose, paralacto-N-neÓhexaose, lacto-N-octaose, lacto-R-neooctaose,, so-laGto*N-ooiaose. para-. lacto-N-octaose and lacto-N-decaose. The expression “at least one fucosylated oligosaccharide” and “at least one N-acetylated oligosaccharide” means “at least one type of fucosylated oligosaccharide” and “at least one type of N-acetylated oligosaccharide.” An “HMO precursor” is a fundamental component involved in the manufacture of HMOs, such as sialic acid and / or ofucose. A "sialylated oligosaccharide" is a charged oligosaccharide containing sialic acid, that is, an oligosaccharide that has an acid residue. It has an acidic nature. Some examples are 3-SL (3' sialillactose) and 6-SL (6' sialillactose). The term “prebiotic” means non-digestible carbohydrates that beneficially affect the host by selectively stimulating the growth and / or activity of healthy bacteria such as bifidobacteria in the human colon (Gfeon GR Roberfhtáf MB. Dietary modification of the human colon: introducing the concept of prebiotics. J Nntr. 1995'125:1401-12). The term “probiotic” means microbial preparations or cell components with a beneficial effect on the health or well-being of the host. (Salminen S, Ouwehand A, 8enno Y, et al., Probiotics: how they should be defined. Trends Food Sol. Technopl 1999:10107-10). Microbial cells are generally bacteria or yeasts. Probiotics can be in a live (replicating) form or in a non-replicating form. The term “Mufc” should be understood as a colony-forming unit. All percentages are by weight unless otherwise stated. Additionally, in the context of the invention, the terms “comprising” or “comprising” do not exclude other possible elements. The composition of the present invention, which includes the various embodiments described herein, may comprise, consist of, or essentially consist of the essential elements and limitations described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise, depending on the needs. Composition form! The nutritional composition of the present invention may be in solid form (e.g., powder) or in liquid form. The quantity of the various ingredients (e.g., oligosaccharides) may be expressed in g / 100 g of the composition on a dry weight basis when in solid form, e.g., a powder, or as a concentration in g / L of the composition when in liquid form (the latter also encompassing a liquid composition that may be obtained from a powder after reconstitution in a liquid, such as bedding, water, etc., a reconstituted infant formula, a maintenance / follow-up formula, a growing-up milk, an infant cereal product, or any other formulation designed for infant nutrition).When g / l is used in reference to a (dry) powdered product, the quantity of g / l refers to the amount present in liquid form after reconstitution into a ready-to-use product, in a manner suitable for the intended use (i.e., according to the instructions). The nutritional composition according to the invention may be, for example, an infant formula, a starter infant formula, a maintenance or follow-on formula, a fortifier such as a human milk fortifier, or a supplement. In one embodiment, the nutritional composition of the invention is a growing-up milk. Less preferably, the invention could also be applied to a baby food and an infant cereal composition. In one embodiment, the nutritional composition of the invention is a complete nutritional composition (meeting all or most of the subject's nutritional needs). In another embodiment, the nutritional composition is a supplement or fortifier intended, for example, to supplement human milk or to supplement an infant formula or a follow-on / maintenance formula. In some particular embodiments, the composition of the invention is an infant formula, a fortifier, or a supplement that may be intended for the first 4, 6, or 12 months of age. In a preferred embodiment, the nutritional composition of the invention is an infant formula. In fact, it is believed that the nutritional intervention of the invention may be most effective when implemented at an early stage of life (e.g., the first 1, 4, or 12 months of age), as it has a greater impact on pancreatic development and maturation and, therefore, on insulin synthesis and glucose management, especially later in life. In some other embodiments, the nutritional composition of the present invention is a fortifier. The fortifier may be a breast milk fortifier (e.g., a human milk fortifier) ​​or a formula fortifier such as an infant formula fortifier or a follow-on / maintenance formula fortifier. When the nutritional composition is a supplement, it can be provided in unit doses. In such cases, it is particularly useful to define the target amount of oligosaccharides and, optionally, other oligosaccharides in terms of the daily dose to be administered to the infant or young child, as described above. The nutritional composition of the present invention may be in solid (e.g., powder), liquid, or gelatinous form. In one specific formulation, the nutritional composition is a powdered supplement provided in a sachet or syrup. When the supplement is in powder form, it may contain a carrier. However, carrier-free supplementation is preferred. When the supplement is in syrup form, the HMOs are dissolved or suspended, preferably, in acidified water with stratum corneum. Supplement In another embodiment, the composition of the invention may be a supplement. The supplement may be in the form of tablets, capsules, lozenges, or a liquid, for example. The supplement may further contain protective hydrocolloids (such as gums, proteins, modified starches), binders, film-forming agents, encapsulating agents / materials, wall / shell materials, matrix compounds, coatings, emulsifiers, surface-active agents, solubilizing agents (oils, fats, waxes, ethyls, etc.), adsorbents, carriers, fillers, co-compounds, dispersing agents, wetting agents, processing aids (solvents), flow agents, flavor-masking agents, weighting agents, gelling agents, and gelling agents.The supplement may also contain excipients and diluents, conventional pharmaceutical additives and adjuvants, including, but not limited to, water, gelatin of any origin, vegetable gums, lignin sulfonate, talc, sugars, starch, gum arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifying agents, regulators, lubricants, colorants, wetting agents, fillers, and the like. In addition, the supplement may contain an organic or inorganic carrier material suitable for oral or parenteral administration, as well as vitamins, trace minerals, and other micronutrients in accordance with the 26 recommendations of government agencies, such as the USRDA. Composition administration regime In some embodiments, the composition according to the invention may be for use before and / or during the weaning period. The nutritional composition can be administered (or given or fed) at a certain age and for a period that depends on the needs. The nutritional composition can, for example, be administered immediately after the birth of infants. The composition of the invention can also be supplied during the first week of the infant's life, or during the first 2 weeks of life, or during the first 3 weeks of life, or during the first month of life, or during the first 2 months of life, or during the first 3 months of life, or during the first 4 months of life, or during the first 6 months of life, or during the first 8 months of life, or during the first 10 months of life, or during the first year of life, or during the first two years of life, or even longer. In some particularly advantageous embodiments of the invention, the nutritional composition is supplied (or administered) to an infant within the first 4, 6, or 12 months of the infant's life. In some other modalities, the nutritional composition of the invention is administered for a few days (e.g., 1, 2, 3, 5, 10, 15, 20...)..), or a few weeks (e.g., 1, 2, 3, 4, 5, 6, 7, 8, & 10...), or a few months (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.,.) after birth. This may be especially the case when the infant is premature, but not necessarily. In one embodiment, the composition of the invention is given to the infant or young child as a supplement to breast milk. In some embodiments, the infant or young child receives breast milk for at least the first 2 weeks, or the first 1, 2, 4, or 6 months. In one embodiment, the nutritional composition of the invention is given to the infant or young child after such a period of maternal nutrition, or is supplied together with such a period of breast milk nutrition. In another embodiment, the composition is supplied to the infant or young child as the sole or primary nutritional composition for at least a period of time, e.g., after the 11, 2, or 4th month of life, for at least 1, 2, 4, or 6 months. Other ingredients Probiotics The nutritional composition of the present Invention may further comprise at least one probiotic (or probiotic strain), such as a probiotic bacterial strain. The most commonly used probiotic microorganisms are mainly bacteria and yeasts of the following genera: Lactobacillus spp., Streptococcus spp., Enterococcus spp., Streptococcus spp., and Schaemmyces spp. In some specific formulations, the probiotic is a probiotic bacterial strain. In some specific formulations, this is particularly SWobacterra and / or Laatobaciffr. Suitable probiotic bacterial strains include Lactobacillus rhamnasus ATCC 53103 available from Valió Oy of Finland under the trademark LGG, Lactobacillus rhamnosus CGMCC 1.3724, Lactobacillus paracaea CNCM 1-2116, Lactobacillus M225, and Stopcoccus sativa DSM 13084 sold by BUS Technologies Limited of New Zealand under the designation kl2, β / WdoJbactenum / acós CNCM 1-3446 sold internationally by the Danish company Christian Hansen under the trademark Bb 12, Síódoóactenum longum ATCC BAA-999 sold by Morinaga Milk Industry Co. Ltd, of Japan under the trademark B8536, Bifídobscíeríum breve sold by Maniaco under the trademark Bb-03, Síífdobacfedum breva sold by Morinaga under the trademark M-16V, BWobactóouór ihfanbs sold by Procter & Gamble Co. under the trademark Bifantis and Bifidobaeterium breve sold by the Rosell Institute (Lailemand) under the trademark R0070. The nutritional composition according to the invention may contain from 103 to 1012ufe of a probiotic strain, more preferably between 107 and 1012ufe 5 such as between 10® and 10'® ufe of probiotic strain per g of composition on a dry weight basis. In one embodiment, the probiotics are viable (i.e., they are alive; i.e., they are capable of replicating). In another embodiment, the probiotics are non-replicating (i.e., they are inactivated). The probiotics may have been rendered non-replicating (inactivated) by any known target treatment in the art, and preferably such treatment comprises or consists of heat treatment. In some other embodiments, there may be both viable and inactivated probiotics. Probiotic components and metabolites may also be added. Source of carbohydrate The nutritional composition according to the present invention generally contains a source of carbohydrate. This is particularly preferred when the nutritional composition of the invention is an infant formula. In this case, any carbohydrate source conventionally found in infant formulas may be used, such as lactose, sucrose, maltodextrin, starch, and mixtures thereof, although lactose is one of the preferred carbohydrate sources. Source of iipido The nutritional composition according to the present invention generally contains a source of lipids. This is particularly relevant if the nutritional composition of the invention is an infant formula. In this case, the lipid source can be any lipid or fat suitable for use in infant formulas. Some suitable fat sources include palm oil, structured triglyceride oil, high oleic sunflower oil, high oleic safflower oil, and medium-chain triglyceride oil. The essential fatty acids linoleic acid and α-linolenic acid can also be added, as well as small amounts of oils containing large amounts of preformed arachidonic acid and docosahexaenoic acid, such as fish oils or microbial oils.The fat source may have an n-6 to n-3 fatty acid ratio of approximately 5:1 to approximately 15:1; for example, approximately 8:1 to approximately 10:1. Source of protein The nutritional composition according to the invention generally contains a source of protein. In some embodiments, the protein may be in an amount of 1.6 to 3 g per 100 kcal. In some embodiments, especially when the composition is intended for premature infants, the amount of protein may be between 2.4 and 4 g / 100 kcal or more than 3.6 g / 100 kcal. In some other embodiments, especially when the composition is an infant formula, the amount of protein may be less than 2.0 g per 100 kcal, e.g., between 1.8 and 2 g / 100 kcal, or in an amount less than 1.8 g per 100 kcal. The type of protein is not considered critical to the present invention, provided that the minimum requirements for essential amino acid content are met and satisfactory growth is ensured. Therefore, protein sources based on whey, casein, and mixtures thereof, as well as soy-based protein sources, may be used. With regard to whey proteins, the protein source may be based on acid whey or sweet whey, or mixtures thereof, and may include alpha-lactalbumin and beta-lactoglobulin in any 5. Desired proportion. In some advantageous embodiments, the protein source is predominantly whey (i.e., more than 50% of the proteins are derived from whey proteins, such as 60% or 70%). The proteins may be intact or hydrolyzed, or they may be a mixture of intact and hydrolyzed proteins. By the term "intact" it is understood that the majority of the proteins are intact, i.e., the molecular structure is not altered, for example, at least 80% of the proteins are unaltered, such as at least 85% of the proteins are unaltered, preferably at least 90% of the proteins are unaltered, 10% 15% 20% even more preferably at least 95% of the proteins are unaltered, such as at least 98% of the proteins are unaltered. In one particular embodiment, 100% of the proteins are unaltered.The term “hydrolyzed” means, in the context of the present invention, a protein that has been hydrolyzed or broken down into its component amino acids. Proteins may be completely or partially hydrolyzed. It may be convenient to supply partially hydrolyzed proteins (degree of hydrolysis between 2 and 20%), for example, for infants or young children considered to be at risk of developing cow's milk allergy. If hydrolyzed proteins are 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 the enzymatic hydrolysis of the whey fraction in one or more stages. If the whey fraction used as the starting material is substantially lactose-free, the protein is found to suffer much less blockage during the hydrolysis process.This makes it possible to reduce the degree of blockage of the Power Plant from approximately 15% by weight of total 25% to less than approximately 10%. lysine weight' for example, approximately 7% by weight of lysine, which greatly improves the nutritional quality of the protein source. In one embodiment of the invention, at least 70% of the proteins are hydrolyzed, preferably at least 80% of the proteins are hydrolyzed, such as at least 85% of the proteins are hydrolyzed, even more preferably at least 90% of the proteins are hydrolyzed, such as at least 95% of the proteins are hydrolyzed, particularly at least 98% of the proteins are hydrolyzed. In one particular embodiment, 100% of the proteins are hydrolyzed. In one particular modality, the proteins in the nutritional composition are hydrolyzed, either completely or partially. The degree of hydrolysis (DH) of the protein can be between 8 and 40, or between 20 and 60, or between 20 and 80, or more than 10, 20, 40, 60, 80, or 90. The protein component can be replaced, alternatively, by a mixture of free amino acids, for example, for premature or low birth weight infants. The free amino acids can be obtained by complete protein hydrolysis (DH 100) or they can be synthetic amino acids. In one particular embodiment, the nutritional composition according to the invention is a hypoallergenic composition. In another particular embodiment, the composition according to the invention is a hypoallergenic nutritional composition. 20 Vitamins and minerals The nutritional composition of the invention may also contain all the vitamins and minerals understood to be essential in the daily diet and in nutritionally significant amounts. Minimum requirements have been established for certain vitamins and minerals; examples of minerals, vitamins, and 25 other nutrients optionally present in the composition of the invention include vitamin 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 amounts of specific minerals and other vitamins will vary depending on the target population. Other nutrients: If necessary, the nutritional composition of the invention may contain emulsifiers and stabilizers, such as soy, lecithin, citric acid esters, mono- and diglycerides, and the like. The nutritional composition of the invention may also contain other substances that may have a beneficial effect, such as lactoferrin, nucleotides, nucleosides, and the like. The nutritional composition of the invention may also contain 15 carotenoid(s). In some particular embodiments of the invention, the nutritional composition of the invention does not comprise any carotenoids. Other oHqosaccharides The nutritional composition according to the present invention may further comprise at least one other oligosaccharide (i.e., other than the fucosylated oligosaccharide(s) necessarily present in the composition) and / or at least one fiber and / or at least one precursor thereof. The other oligosaccharide and / or fiber and / or precursor thereof may be selected from the list comprising N-aminoglycan oligosaccharides, (other) fucosylated oligosaccharides, fructooligosaccharides (GOS), fructooligosaccharides (EOS), inuin, xylooligosaccharides (XQS), polydextrose, sialylated oligosaccharides, sialic acid, fucose, and any combination thereof. They may be present in an amount between Q and % by weight of the composition. In one particular embodiment, the nutritional composition may further contain at least one BMO (bovine milk oligosaccharide). Additionally, suitable commercial products can be used from the oligosaccharides included in the oligosaccharide mixture to prepare the nutritional compositions according to the invention 5, including combinations of FOS with Inulin such as the product sold by BENEO under the registered trademark Oraftí, or polydextrose sold by Tete & Lyíe under the registered trademark STA-ÜT8B. Sialylated oligosaccharide In another particular embodiment, the nutritional composition according to the invention may comprise sialylated oligosaccharide(s). There may be one or more types of sialylated oligosaccharide(s). The sialylated oligosaccharide(s) may be selected from the group comprising 3'-sialillactose (3-SL), 6'-sialillactose (6-SL), and any combination thereof. In some embodiments of the invention, the composition comprises 3-SL and 6-SL. In some particular embodiments, the ratio between 3'-sialillactose (3-SL) and 6'-sialillactose (6-SL) may be in the range of 5:1 to 1:10, or 3*1 and 1:T, or 1:1 to 1:W, In some specific forms, the sialylated oligosaccharide of the composition is 6' sialillactose (6-SL), The sialilated oligosaccharide(s) can be isolated by chromatographic or filtration technology from a natural source such as animal milk. Alternatively, these can be produced by biotechnological means using specific sialyltransferases or sialidases, neuraminidases, either through enzyme-based fermentation technology (recombinant or natural enzymes), by chemical synthesis, or by microbial fermentation technology. In the latter case, the microbes can express their natural enzymes and substrates or can be engineered to produce the respective substrates and enzymes. Simple and / or mixed microbial cultures can be used. Sialyl oligosaccharide formation can be initiated by acceptor substrates starting from any degree of polymerization (DP), from DP-1 onward. Alternatively, sialyl lactoses can be produced by chemical synthesis from lactose and free N'-acetyluramic acid (sialic acid). Sialyl lactoses are also commercially available from, for example, Kyowa Hakko Kpgyo. Japan. In another preferred embodiment of the invention, the nutritional composition may comprise 0.005-5 g / l of sialylated oligosaccharides, or 0.008-2.5 g / l, or 0.01-1 g / l, or 0.02-0.7 g / l, for example, 0.03-0.5 g / l. The nutritional composition according to the invention may contain 0.004-3.8 g of sialylated oligosaccharides per 100 g of the composition on a dry weight basis, e.g., 0.006-1.9 g or 0.008-0.8 g or 0.015-0.5 g, e.g., 0.023-0.4 g of sialylated oligosaccharides per 100 g of the composition on a dry weight basis. In some particular embodiments of the present invention, the nutritional composition comprises sialoylated oligosaccharide(s) in an amount less than 0.1 g / 100 g of composition on a dry weight basis. In one particular embodiment, the sialylated oligosaccharide is provided in the nutritional composition of the present invention in such an amount that normal consumption of the nutritional composition would provide the infant or young child, respectively, consuming it with a total daily dose of 0.003-6.5 g, preferably 0.005- 3.3 g 0.006-1.3 g 0.01-0.9 g, for example, 0.018-0.65 g per day. In some particular embodiments of the present invention, the nutritional composition does not contain any sialylated oligosaccharide(s). The nutritional composition according to the present invention may also optionally include an oligosaccharide precursor. There may be one or more oligosaccharide precursors. For example, the precursor of the human milk oligosaccharide is sialic acid, fucose, or a mixture thereof. In some particular embodiments, the composition comprises sialic acid. In particular examples, the nutritional composition comprises 0 to 3 g / l of glycosaccharide precursor(s), or 0 to 2 g / l, or 0 to 1 g / l (or 0 to 0.7 g / l, or 0 to 0.5 g / l from 0 to 0.3 g / l, or 0 to 0.2 g / l of oligosaccharide precursor(s). The composition according to the invention may contain from 0 to 2.1 g of oligosaccharide precursor(s) per 100 g of the composition on a dry weight basis, e.g. from 0 to 1.5 g, from 0 to 0.8 g, or from 0 to 0.15 g of oligosaccharide precursor(s) per 100 g of the composition on a dry weight basis. Oligosaccharides phacosyls2 The nutritional composition of the present invention contains at least one human milk oligosaccharide. This comprises at least one fucosylated oligosaccharide. There may be one or more types of fucosylated oligosaccharide(s). The fucosylated oligosaccharide(s) can, in fact, be selected from the list comprising 2fucosiliactose, 3fucosiliactose, difucosiliactose, lacto-N-ducopentaose (such as lacto-N-fucopentaose I, lacto-N-fucopentaose II, lacto-M-fucopentaose III, lacto-N-fucopentaose V), lacto-N-fucohexaose, factoro-N-difucohexaose I, fucosillacto-N-hexaose, fucosillacto-N-neohexaose (such as fucosillacto-N-neohexaose I, fucosillacto-N-neohexaose II), 20 difucosillacto-N-hexaose I, difucolacto-N-neohexapse, difucosiliacto-N-neohexapse I, difucosylact-N-neohexaose II, fucosyl-paralacto-N-hexaose, tri-fuco-paralacto-N-hexaose I and any combination of these. In some particular forms, the fucosylated oligosaccharide comprises an epitope 'Mucosyl'. It can be selected, for example, from the list comprising 2' fucosylactose, difucosylactose, lacto-N-tucopentaose, lacto-M-fucohexaose, 5. Lacto-N-difucohexaose, fucosyl lacto-N-hexaose, fucosyl lacto-N-neohexaose, difucosyl lacto-N-hexose, difucosyl lacto-N-neohexaose, difucosyl-fucosyl-para-lacto-N-hexaose, and any combination thereof. In a particularly preferred embodiment, the nutritional composition according to the invention comprises 2-fucosyl lactose (or 2FL, or 2TL, or 2-FL, or 2-FL). 2FL is believed to be the optimum fucosylated oligosaccharide in the context of the present invention, which is naturally contained in human breast milk in a relatively significant amount. In one particular embodiment, there is no other type of fucosylated oligosaccharide 1G 15 than 2'-fucosyl lactose, i.e., the nutritional composition of the invention comprises only 2'-fucosyl lactose as the fucosylated oligosaccharide. The fucosylated oligosaccharide(s) can be isolated by chromatography or filtration technology from a natural source such as animal milk.Alternatively, it can be produced biotechnologically using specific fucosyltransferases and / or fucosidases, either through enzyme-based fermentation technology (using recombinant or natural enzymes) or microbial fermentation technology. In the latter case, the microbes can either express their natural enzymes and substrates or be modified to produce substrates and enzymes, respectively. Simple and / or mixed microbial cultures can be used. The formation of the fucosylated oligosaccharide can be initiated by acceptor substrates starting from any degree of polymerization (DP), from DP ~ 1 onwards. Alternatively, fucosylated oligosaccharides can be produced by chemical synthesis from lactose and free fucose. Fucosylated oligosaccharides are also available, for example, from Kyówá, Hakkó, and Kogyo in Japan. The fucosylated gaseous oils can be found present in the. The fucosylated oligosaccharide(s) according to the present invention are present in a total amount of 0.75-1.65 g / l of the composition. In some embodiments, the fucosylated oligosaccharide(s) may be present in a total amount of 0.005-5 g / l of the composition, such as 0.01-3 g / l, 0.02-2 g / l, 0.1-2.5 g / l, 0.15-2 g / l, or 0.25-1.9 g / l of the composition. In one particular embodiment, the fucosylated oligosaccharide(s) are present in a total amount of 1 g / l of the composition. In another particular embodiment, the fucosylated oligosaccharide(s) are present in a total amount of 0.25 or 0.26 g / l of the composition. In one embodiment, the fucosylated oligosaccharide(s) is / are in a total amount greater than 0.1 g / l, optionally less than 1 g / l, greater than 0.2 and less than 0.8 g / l. In another embodiment, the fucosylated oligosaccharide(s) is / are in a total amount of at least 0.1 g / l, at least 0.25, at least 0.26, at least 0.5, at least 0.7, at least 0.8, at least 1, at least 1.25, at least 1.5 or at least 2 g / l. The fucosylated oligosaccharide(s) may be present in the nutritional composition in a total amount of 0.004-3.8 g / 100 g of composition according to a dry weight. The fucosylated oligosaccharide(s) may be in a total amount of 0.008-2.3 g / 100 g of the composition, such as 0.015-1.5 g / 100 g, or 0.08-1.9 g / 100 g or 0.12-1.5 g / 100 g or 0.15-1.5 g / 100 g or 0.19-1.5 g / 100 g of the composition. In one particular embodiment, the fucosylated oligosaccharide(s) is / are present in a total amount of 0.075 or 0.78 g / 100 g of the composition. In another particular embodiment, the fucosylated oligosaccharide(s) is / are present in a total amount of 0.2 g / 100 g of the composition. In one particular embodiment, the fucosylated oligosaccharide(s) is / are present in a total amount of at least 0.01 g / 100 g, at least 0.02 g / 100 g, at least 0.05 g / 100 g, at least 0.1 g / 100 g, at least 0.2 g / 100 g, at least 0.25 g / 100 g, at least 0.4 g / 100 g, at least 0.5 g / 100 g, at least 0.75 g / 100 g, at least 0.9 g / 100 g, at least 1 g / 100 g, at least 1.5 g / 100 g, at least 2 g / 100 g, or at least 3 g / 100 g of the. composition. In one particular embodiment, the fucosylated oligosaccharide is provided in the nutritional composition of the present invention in such an amount that normal consumption of the nutritional composition provides the infant or young child, respectively, with a total daily dose of 0.003-6.5 g, preferably 0.006-3.9 g, for example, 0.012-2.6 g per day. It is believed that a minimal amount of fucosylated oligosaccharide is necessary to have the desired effect in a moderate manner. For premature, low birth weight, and small-for-gestational-age infants, the daily dose of fucosylated oligosaccharides is preferably 0.05 to 1 g / kg of body weight per day, preferably 0.06-0.9 g α 0.07-0.8 go 0.08 0.7 g 0.09-0.6 g 0.1-0.5 g 0.2-0.4 g / , with the highest preference, 0.34 g per kg of body weight per day. When both N-acetylated oligosaccharides and fucosilicate oligosaccharides are present, the fucosilicate oligosaccharide(s) and the oligosaccharide(s) N-acetylated oligosaccharide(s) included in the nutritional composition according to the invention are typically present in a ratio of N-acetylated oligosaccharide(s):fucosylated oligosaccharide(s) of 1:20 to 2:1, preferably from 1:15 to 1:1, most preferably from 1:10 to 1:2. In a particularly advantageous embodiment, this ratio is (or is approximately) 1:2, 1:5 or 1:10. In one particular embodiment of the present invention, the nutritional composition comprises Z-fucosillactose (2EL) and no other oligosaccharide. In a separate embodiment of the present invention, the nutritional composition comprises 2fucosillactose (2FL) and another oligosaccharide, preferably a human milk oligosaccharide, more preferably lacto-N-neotetraose (LNnT) or LNT (lacto-N-tetraose). In a particular embodiment of the present invention, the nutritional composition comprises 2Mdcosillactose (2FL) and lacto-N-neotetraose (LNnT). In one specific embodiment, the nutritional composition of the present invention comprises a mixture of oligosaccharides consisting of 2'-fucosyltetraose (2FL) and lacto-N-neotetraose (LNnT). In other words, the nutritional composition of the invention comprises only 2'-fucosyltetraose (2-FL) as the fucosylated oligosaccharide and only lacto-N-neotetraose (LNnT) as the N-acetylated oligosaccharide. N-acetylated oligosaccharide(s) In one embodiment, the composition of the invention comprises at least one N-acetylated oligosaccharide. The N-acetylated oligosaccharide is preferably LnNT. The inventors have discovered, without limiting themselves to theory, that LnNT develops the best interactions with the intestinal flora and enhances the described effect. In one embodiment, the N-acetiated oligosaccharide is iacto-N-neotetraose (LNnT), lacto-N-tetraose (LNT), para-iacto-N-neohexaose (para-LNnH), dlsialylacto-Ntetraose (DSLNT) or any combination thereof. 1§ In one embodiment, the N-acetiated oligosaccharide(s) is / are present in a total amount of between 0.025-1.5 g / l of the composition, preferably at least 0.1 g / l or at least 0.25 g / l, and / or in a total amount of between 0.003-0.23 g / 100 g, preferably at least 0.015 g / 100 g or at least 0.03 g / 100 g of the composition on a dry weight basis. N-acetate oligosaccharide(s) can be chemically synthesized by enzymatic transfer of sachet units from donor entities to acceptor entities using glycosyltransferases as described, for example, in U.S. Patent No. 5,288,637 and Patent No. WO 96 / 10086. Alternatively, LNT and LNnT can be prepared by chemical conversion of cellohexoses (e.g., free fructose or fructose bound to an oligosaccharide (e.g., lactulose)) into N-acetylhexosamine or an oligosaccharide containing N-acetylhexosamine as described in Wrodnigg, TM; Stute, AX (1999) Angew. Ghem. int Ed. 38:827-828. The N-acetylhexosamine produced in this way can then be transferred to lactose as the acceptor entity. In a particularly advantageous embodiment of the present invention, the N-acetylated oligosaccharide(s) are present in the nutritional composition in certain specific amounts. The term "amount" refers to the total amount of each of these two components in the nutritional composition unless otherwise specified. It does not, therefore, refer to an individual amount except when there is only one type of these components (in which case, both the total and the individual amounts are equal). The same applies to all compounds / ingredients of the invention. By way of illustration, if there is only one (i.e., only one type of) N-acetylated oligosaccharide in the composition (e.g., LNnT), its individual amount (and thus the total amount of N-acetylated oligosaccharides) will be in the range of 0.75–1.65 gA If there are several (i.e., several types of) N-acetylated oligosaccharides, their individual amount will be lower (e.g., if there are 2 different types of N-acetylated oligosaccharide, e.g., LNnT * LNT, each may be, for example, in an individual amount of 0.5 g / l), but the total amount of N-acetylated oligosaccharides will be in the range of 6.75-1.65 g / l. In one particular embodiment, the N-aoethylated Oligosaccharide is provided in the nutritional composition of the present invention in such an amount that normal consumption of the nutritional composition would provide the Infant or young child, respectively, consuming it with a total daily dose of 0.003-3.9 g, preferably 0.006-3.25 g, 0.03-1.95 g, 0.03-1.3 g, or 0.03-1 g, for example, 0.05-1 g per day. For premature, low birth weight and small for gestational age infants, the daily dose is preferably 0.005 to 0.1 g of body weight per day, preferably 0.034 g per kg of body weight per day. Use and effect of the composition A first object of the present invention is, therefore, a nutritional composition comprising at least one fusylated oligosaccharide, optionally also at least one N-acetylated oligosaccharide, for use in enhancing pancreatic development and / or pancreatic maturation in infants. It is believed that pancreatic development and pancreatic maturation are much more closely related and linked, as the functionality of biosynthesis, storage, and excretion (or active secretion) of hormones and enzymes by the mature organ depends on its development. In one embodiment, the nutritional composition comprises at least one fucosylated digoxaccharide that is present in a total amount of between 0.05-3 g / l of the composition, preferably at least 0.2 g / l to at least 0.5 g / l, and / or in a total amount of between 0.007-0.45 g, preferably at least 0.03 g / L or at least 0.075 g / L of the composition on a dry weight basis. Target age In one embodiment, the nutritional composition of the invention is specifically intended and designed for infants between 0 and 12 months of age, preferably between 0 and 6 months. It is believed that early intervention (below 6 or below 12 months of age) has a greater potential effect. In another embodiment, the invention is used for toddlers (children between 1 and 3 years of age) up to 3 years of age. Without being limited to theory, the inventors believe that the effect of the invention can be expected to be positive not only for infants but also for toddlers up to 3 years of age (based on the corresponding age of rats extrapolated to infants / toddlers in the experiments described herein). Effect In one embodiment, the nutritional composition induces improved pancreatic development or maturation by induction, mediation, or accompanying an improvement or increase in the level of insulin biosynthesis by the infant's pancreatic cells. "Improvement" is understood to mean an increase in the level of insulin biosynthesis (compared to a subject not receiving the nutritional composition of the invention). This improvement may be related to an increase in the number of pancreatic β cells (which produce insulin), and / or their capacity to synthesize insulin (in high quantities), and / or, more generally, their degree of maturation. Crucially, this increase in biosynthesis may or may not be accompanied by an increase in insulin secretion or excretion by the pancreas.Without limitation to the theory, in fact, it is believed that insulin biosynthesis and secretion are regulated by different effects. It is also believed that increasing the level of biosynthesis by pancreatic beta cells provides an improved effect on health in the medium and long term (compared to increased secretion) as secretion (without increased biosynthesis) reaches a plateau very quickly ("empty receptacle effect"). The inventors conclude that such enhanced maturation of pancreatic beta cells and increased biosynthesis helps improve glucose management in infants during the administration period and / or throughout childhood and / or later in life. Therefore, related negative health conditions such as the risk of type 2 diabetes, obesity, and / or overweight are reduced and prevented. Beyond theory, the inventors believe that increasing insulin biosynthesis by pancreatic cells is a better predictor of short- and long-term health benefits compared to simply promoting insulin secretion. Promoting insulin secretion cannot have the same optimal benefit as those limited by the plateau effect corresponding to the limiting amount of insulin biosynthesized by pancreatic cells (secretion can only make the biosynthesized amount available; whereas increased biosynthesis inevitably leads to a higher amount of circulating insulin in the longer term). In one embodiment, the infants are needy subjects and / or those at risk of underdeveloped pancreases and / or are born prematurely and / or suffer from intrauterine growth restriction (IUGR) and / or are born with low birth weight (L8W), very low birth weight (VL8W), or extremely low birth weight (EL8W). Not limited to theory, the inventors believe that the more fragile the infants are (e.g., the lower the birth weight, or the more premature they are), the more the infants can benefit from the invention. In fact, it is believed that such infants struggle to produce (or are at risk of failing to produce) the optimal amount of insulin (due to the immaturity of their pancreatic function). Such subnormal pancreatic function is extremely difficult to regulate but can induce multiple pathologies associated with glucose management. Among these, high blood glucose / low plasma insulin may be observed in the short term.In the long term, it is associated with type 2 diabetes, risk of obesity and / or overweight, and all related cardiovascular diseases. The inventor has discovered that the proposed nutritional intervention can lead to a faster / more optimal establishment of pancreatic function, particularly in at-risk infants, and a reduction in the risk of associated diseases or pathological conditions (both long-term and short-term). Preparation of the composition The nutritional composition according to the invention can be prepared in any suitable manner. Now, one composition will be described as an example. For example, a formula such as infant formula can be prepared by mixing together the protein source, carbohydrate source, and fat source in appropriate proportions. If used, emulsifiers can be added at this point. Vitamins and minerals can be added at this point, but are usually added later to avoid thermal degradation. Any lipophilic vitamins, emulsifiers, and the like can be dissolved in the fat source before mixing. Water, preferably reverse osmosis water, can then be mixed in to form a liquid mixture. The water temperature is conveniently in the range of approximately 50°C to approximately 80°C to aid in the dispersion of the ingredients. Commercially available liquefying agents can be used to form the liquid mixture. The fucosylated oligosaccharide(s) and / or the N-acetylated oligosaccharide(s) may be added at this stage, especially if the final product will be in liquid form. If the final product is to be a powder, they may also be added at this stage, if desired. Then, the liquid mixture is homogenized, for example, in two stages. The liquid mixture can then be heat-treated to reduce the bacterial load by rapidly heating it to a temperature in the range of approximately 80°C to approximately 150°C for a duration of approximately 5 seconds to approximately 5 minutes, for example. This can be accomplished by steam injection, an autoclave, or a heat exchanger, such as a plate heat exchanger. The liquid mixture can then be cooled to between approximately 6°C and approximately 65°C, for example, by rapid cooling. The liquid mixture can then be homogenized, for example, in two stages, between approximately 5 and 10 MPa and approximately 30 MPa in the first stage, and between approximately 2 and 16 MPa in the second stage. The homogenized mixture can then be further cooled to add any heat-sensitive components, such as vitamins and minerals. The pH and solids content of the homogenized mixture are conveniently adjusted at this point. If the final product is to be a powder, the homogenized mixture is transferred to a suitable drying apparatus such as a spray dryer or a freeze dryer and converted into a powder. The powder should have a moisture content of less than approximately 5% by weight. The tosylated oligosaccharide(s) and the N-acetylated oligosaccharide(s) may also be added at this stage by mixing them dry or alternatively by mixing them into a syrup in crystal form, together with the prototic strain(s) (if used), and the mixture is spray dried or freeze-dried. If a liquid composition is preferred, the homogenized mixture can be sterilized and then aseptically packaged in suitable containers, or it can first be packaged in the containers and then retortized. Target subjects for composition The nutritional composition of the present invention can also be used in an infant or young child who was born by cesarean section or who was born vaginally. The nutritional composition according to the invention is for use in infants or young children. Infants or young children may be born at term or preterm. In one particular embodiment, the nutritional composition of the invention is for use in infants or young children who were born preterm, who have a low birth weight, and / or were born small for gestational age (SGA). In one particular embodiment, the nutritional composition of the invention is for use in premature infants, infants who have a low birth weight, and / or infants who were born small for gestational age (SGA). It is believed that the infant born prematurely or born with low birth weight necessarily achieved a lower stage of development in utero and, therefore, may benefit from the nutritional intervention of the invention. Infants in need of optimal pancreatic maturation or development are particular targets for the invention. Such infants may present with a risk of, or measurable underdevelopment or under-maturation of the pancreas at birth. Consequently, such infants may benefit most from the present invention. The invention helps the individual in need to compensate for the underdevelopment or under-maturation of their pancreatic function by promoting (induced by the nutritional intervention of the invention) faster post-birth maturation / development and, therefore, promoting optimal pancreatic cell function, in particular, promoting insulin biosynthesis. Premature infants (infants born before the normal term), infants with low birth weight, or infants with growth retardation are particular targets of the invention. Generally, when infants are more premature or have a lower birth weight, the benefits of the invention will be greater in their short- and long-term glucose management. No reference to prior art documents in this specification should be deemed to be an admission that the prior art is widely known or forms part of the common general knowledge in the field. The invention will now be described in greater detail. It should be noted that the various aspects, features, examples, and modalities described in this application may be compatible and / or combined with each other. Examples The following examples illustrate some specific embodiments of the composition for use according to the present invention. The examples are provided for illustrative purposes only and should not be construed as limitations of the present invention. Example 1 An example of the composition of a nutritional composition (e.g., an infant formula) according to the present invention is provided in Table 1 below. This composition is provided for illustrative purposes only. Table 1: Composition of the infant formula in Example 1 Nutrients per 100 fecal · j per liter Energy (fecal) 100 j 070 Pnstein (g) 1.83 | 12 3 j Fat (g) 5.3 | 55 7 i Unoteic acid (g) 0.79 I 5.3 Ac:do (mg) 101 | 675 Lactose (g) n.¿ | 74.7 i Minerals (g) 0.37 [ 2.5 i Na(mg) 23 I n>0 Ϊ K (mg) 89 J 530 i 01 (mg) 64 | 430 Ca (mg) 63 ί 410 | P (mg) 1 31 1 2?o Mg(mg) 7 I 50 Mn (pg) 8 60 Se tyg} 2 13 Vitamin A mg RE ii 105 70!) Vitamin D (pg} ΐ 1.5 10 Vitamin E (mg TE) 0.8 5.4 Vitamin K1 (pg) j 8 54 Vitamin C (mg) j 10 67 Vitamin 81 (mg) 0.47 Vitamin 62 (mg) i 0.15 1 ü Ntacin (mg) i 8.7 Vitamin S6(mg) 0:075 0.50 Folic acid» (pg) 9 60 Pantothenic acid (mg) 0,-15 3 Vitamin 612 (ug) 0.2 2 Biotin (pg) 2.2 15 Celine (mg) 10 | 67 Fe (ng) 1.2 | 8 l(pg) 15 100 Cu (mg) 0.06 0.4 Zn (mg) 0.75 5 Oliqosacharitios i ; , 0.075 i 2FL(g) ÍHMQ1 i 0.5 Example 2; An example of the composition of a nutritional composition (e.g., an infant formula) according to the present invention is provided in Table 2 below. This composition is provided for illustrative purposes only. Table 2: Composition of the infant formula from Example 2 Nutrients per 100 Actual per liter Energy (kcal) 100 670 [ Protein (g) 1.83 12.3 25 | Fat (g) 5.3 35 7 Lineteic acetate (g) C.79 5.3 C-lmoiemic acid (mg) W1 575 Lactose (g) 11.2 74.7 Minerals (g) 0.37 2.5 Na (mg) 23 150 K (mg) 89 590 01 (mg) S 410 P (mg) 31 210 Mg (mg) 7 50 Mn (pg) 8 50 s« (pg) 2 13 Vitamin A (pg RE) 105 700 Wmtaa D(pg) 10 Vitamin E (mg TE) 0.8 5.4 Vitamin 8 Vitamin C (mg) 54) 10 67 Vitamin 81 (mg) 0.07 0.47 Vitamin 82 (mg) 0.15 1.0 Niacin (mg) Vitamin 86 (mg) 0.075 6.7 8.50 Folic acid (pg} θ 60 Pantothenic acid (mg) 183 5. (pg) 0.3 2 Biotin(g) 2.2 15 Choline (mg) 10 67 Fe (mg) 1.2 8 Mus) 15 too Cu tmg) 0.06 0.4 Zn(mg) 0.75 5 HMO 0.5 Example 3 Description of the est^ Three groups of timely pregnant Sprague-Dawtey female rats were purchased from Charles River Laboratories. One group underwent 60% food restriction during the last 10 days of gestation, and their pups were crossbred with respect to normally fed rats. A second group of pregnant females was normally fed, and their pups were crossbred. S among the same group of mothers. Immediately after birth (postnatal day 2 (d“2 j)), the born rat pups, the subjects of the experiment, were assigned to one of the following groups; • IUGR group (negative control; 0=20): IUGR rats fed a normal diet after birth; ♦ IUGR + HMO rats (test groups): During the experiment, these rats were mother-reared for 21 days and supplemented with HMOs (2-FL, LNnT, or a mixture of 2-FL and LNnT). At weaning, they were fed a diet supplemented with the same HMOs; see details below. There were three different groups: i 5 » IU GR / 2FL group (n= 10): supplemented with soto 2-FL; lUGR / LNnT group (n~l 0); supplemented with only LNnT; and - IUGR / HMO blend group (n~10); supplemented with LNnT and 2FL in a weight ratio of 1:2. All rat pups were fed from birth (d=i) until 20 57 days (d«57) based on the following protocol: * di a dO; all groups of rats were breastfed by the mother (breast milk only); * d7 to d21; all rats were breastfed by their mothers (breast milk only). But they were also supplemented with 3 g / kg body weight of HMO in the test groups or maltodextrin for the control group via tube feeding: g / kg of body weight of 2-FL for the IUGR / 2FL group; gf kg of body weight of LNnT, for the lUGR / LNnT group; g / kg of body weight of a mixture of LNnT and 2FL at a weight ratio of 1:2, for the 1UGR / HMO mixture group; • d22 to d57: all rats were fed a diet as detailed in Table 3 below. Table 3: Composition of the diets administered to the different prune trees from d22 to d57 Corn starch Casein ..................................·······—.,······—. Sucrose Amount in the diet of the control group [%) 53.4 20 10 Amount in the diet of Group 2FL [%] 53.4 20 10 ...........--...............T.................................. Amount in the diet of Group 1 Amount in the diet of Group 1 diet of Group 1 of HMQ mixture ___ [%1 53.4 53.4 20 20 10 p Soybean oil 17 f? Mineral mixture Ai N-93-G · ¡3.5 ¡3.§ 7 b 3.5 ¡3.6 Ketin Bstarrate ¡0.25 |Q,25 0.25 ¡0.25 L-Cystine ¡0.3 ¡0.3 Tert-butylhydroqtófwa ©.0014 ¡0 0914 0.3 ¡0.3 0.0014 ¡0.0014 Vitamin Blend AiN-93-VX* 1 Maltodex'rin ¡4.5 1 0 1 4 o..............................F .................... 2FL Ϊ0 ¡4.5 LNnT ~ ¡0 r—— * Dé ResSarcó Diets, Inc .......1.................................. 0 P 4.5 ¡1.5 Rats were sacrificed on day 57 (postnatal day 57 - p57) after a 6-hour fasting period, and the pancreas was dissected and its insulin content extracted using an acid-ethanol solution and quantified using an ELISA kit for ultrasensitive insulin (Crystallno, Downer Grave, IL, USA) with an inter-assay CV of 4.0% Findings After sacrifice (day 57 = p57), the insulin content of the rat pancreas was analyzed and reported in Figure 1. The concentration is expressed as the amount of insulin (in pg) per gram of pancreatic tissue. Control IUGR rats expressed an insulin value of approximately 50 pg of insulin per gram of pancreatic tissue. The LNnT-fed rat group also expressed approximately the same level of insulin. Rats fed 2FL surprisingly expressed significantly higher levels of insulin in their pancreatic tissues. Even more surprisingly, rats fed a mixture of 2FL and LNnT also expressed high levels of insulin in their pancreatic tissues. The inventors concluded that a diet containing 2FL in the specified population enhances the development and / or maturation of pancreatic cells, thereby improving insulin biosynthesis. The invention also concludes that not all HMOs have a similar effect (LNnT alone, for example, does not appear to increase insulin biosynthesis). Surprisingly, the combination of 2FL and LNnT in the diet also increases insulin biosynthesis—tangentially and synergistically compared to 2FL alone (or LNnT alone). At least the presence of LNnT does not inhibit the insulin-synthesis-enhancing effect of 2FL in the diet. Beyond theory, this may indicate that each HMO (2FL, LNnT) utilizes a different mechanism that leads to the enhancement of insulin biosynthesis. Overall, these results show that 2FL alone or in combination with LNnT was successful in increasing insulin biosynthesis. By selecting the most suitable HMO and feeding the subject with the selected HMO, the inventors thus achieved an improvement in pancreatic maturation and, consequently, an increase in insulin secretion. It is shown that a nutritional intervention with the selected bioactive nutrient can induce a medial change in pancreatic insulin content during the pancreatic development phase and can, as such, influence pancreatic maturation. Based on these observations, it is highly likely that the long-term effect can be predicted in such conditions depending on pancreatic maturation and / or the level of insulin biosynthesis. Example 4 A supplement for premature infants is prepared, such as to provide the following daily dose: 0.34 g / kg of body weight per day of 2-FL, and - optionally, 0.034 g / kg of body weight per day of LNnT.

Claims

1. A nutritional composition comprising at least one fucosylated oligosaccharide for use in enhancing pancreatic development and / or pancreatic maturation in infants or young children.

2. The nutritional composition of claim 1 characterized in that at least one fucosylated oligosaccharide is present in a total amount of between 0.053 g / l of the composition, preferably at least 0.2 g / l to at least 0.5 g / l, and / or in a total amount of between 0.007-0.45 g / 100 g, preferably at least 0.03 g / 100 g to less than 0.075 g / 100 g of the composition on a dry weight basis.

3. The nutritional composition of any of the preceding claims characterized in that the fucosylated oligosaccharide is 2FL< 4. The nutritional composition of any of the preceding claims, characterized in that the composition comprises an N-acetiated oligosaccharide. 15 5. The nutritional composition of any of the above claims, characterized in that the N-acetylated oligosaccharide is lacto-N-neotetraose (LNnT), lacto-N-tetraose (LNT), para-l-cto-N-neohe (para-LNnH), disyl-l-lacto-N-tetraose (DSLNT) or any combination thereof.

6. The nutritional composition of any of the above indications, characterized in that the N-acetylated oligosaccharide is present in a total amount of between 0.025-1.5g / l of the composition, preferably at least 0.1g / l or at least 0.25g / l, and / or in a total amount of between 0.003-0.23g / 100g, preferably at least 0.015g / 100g or at least 0.03g / 100g of the composition on a dry weight basis.

7. The nutritional composition of any of the above claims characterized in that the infants are between 0 and 12 months old.

8. The nutritional composition of any of the preceding claims, characterized in that the improvement of pancreatic development or maturation further comprises, is mediated by, or is accompanied by the improvement of the level of insulin biosynthesis by the pancreatic cells of the infant or young child.

9. The nutritional composition of any of the preceding claims for use further in improving glucose handling in infants during the period of administration and / or during childhood and / or later in life, preferably in reducing the risk of type 2 diabetes and / or obesity.

10. the nutritional composition of any of the preceding claims, characterized in that the infants are needy subjects and / or at risk of poor pancreatic development and / or are born prematurely and / or suffer from intrauterine growth retardation (IUGR) and / or are born with low birth weight (LBW), very low birth weight (VLBW), or extremely low birth weight (ELBW).

11. The nutritional composition of any of the preceding claims characterized in that the nutritional composition is an infant formula, or a supplement for infants or young children, or a fortifier for human breast milk, or a follow-on formula, or a growing-up milk.

12. The nutritional composition of any of the preceding claims, characterized in that the composition is to be administered during the first 1, 2, 3, 6, or 12 months of life, and / or to be administered in a quantity and / or for a duration sufficient to induce mediate improvement of pancreatic development or pancreatic maturation of infants.

13. The nutritional composition of any of the above claims characterized by the composition further comprises sislillactoss, preferably 3SL or 6SL.

14. The nutritional composition of any one of the preceding claims, comprising at least one other oligosaccharide(s) and / or fiber(s) and / or precursor(s) thereof selected from the list comprising galactooligosaccharides (GOS), fructooligosaccharides (FOS), xylooligosaccharides (XOS), inulin, polydextrose, sialylated oligosaccharides, sialic acid, teosin, and any combination thereof.

15. The nutritional composition of any one of the preceding claims, the composition further comprising at least one probiotic, live or in a non-replicating form, in an amount of 10s to 100 CFU / g of the composition (dry weight).

16. The nutritional composition of any one of the preceding claims characterized in that the composition is an infant formula, the acetilated HF oligosaccharide is LNnT and the fucosylated oligosaccharide is 2FL, and wherein the infant is a premature infant, optionally the composition is given as food to the infant during the first 6 months of life.ABSTRACT This invention relates to nutritional compositions comprising at least one fucosylated oligosaccharide, preferably 2FL, for use in enhancing pancreatic development and / or pancreatic maturation in infants, and / or enhancing insulin biosynthesis and / or preventing metabolic disorders or associated diseases and / or managing glucose during nutritional intervention or later in life. The composition may be an infant formula. The composition may also comprise at least one N-acetylated oligosaccharide, preferably 10LnNT.