Composition for preventing or treating gastrointestinal infections / inflammations in infants or young children

Abstract

The present invention relates to a composition for use in the prevention or treatment of gastrointestinal infections / inflammation in infants or young children. The present invention relates to a nutritional composition comprising at least one fucosylated oligosaccharide and at least one N-acetylated oligosaccharide in specific proportions for use in the prevention and / or treatment of gastrointestinal infections and / or gastroenteritis in infants or young children.

Description

[0001] This application is a divisional application of PCT application PCT / EP2016 / 054617, filed on March 4, 2016, entitled "Composition for the Prevention or Treatment of Gastrointestinal Infections / Inflammation in Infants or Young Children". The date of entry into the Chinese national phase of the PCT application was September 4, 2017, and the application number was 201680013679.5. Technical Field

[0002] This invention relates to compositions for the prevention and / or treatment of gastrointestinal infections and / or inflammations such as enteritis in infants or young children. Background Technology

[0003] Intestinal infections and / or inflammation are particularly common in infants and young children due to their delicate physical condition, relatively poor hygiene habits, and immature immune defense systems. Defense mechanisms involve establishing a symbiotic microbiome and both innate and adaptive immune systems. In the first two to three years after birth, these defense systems are not fully developed, making infants more susceptible to infection. Therefore, pathogens can overcome the defense mechanisms of infants and young children. For example, in the first year of life, infants will often experience one to four gastrointestinal infections / inflammations.

[0004] The infection could be in the upper gastrointestinal tract, such as the esophagus and / or stomach. It can also be in the lower gastrointestinal tract, such as the small intestine and the entire large intestine (colon). Examples of gastrointestinal infections include enteritis, gastroenteritis, and infectious diarrhea. Intestinal infections can also be associated with intestinal inflammation. Enteritis, gastroenteritis, and infectious diarrhea are examples of this.

[0005] Enteritis refers to an infection of the small intestine. It is usually associated with inflammation of the small intestine. Gastroenteritis, or infectious diarrhea, is a gastrointestinal medical condition involving both the stomach and intestines. It is also usually associated with inflammation of these organs.

[0006] The main symptoms of gastrointestinal infection are diarrhea, vomiting, abdominal pain, and cramps. Other possible symptoms include difficulty feeding, irritability, poor sleep quality, and fatigue. Headache and fever may also occur, especially if the gastrointestinal infection is viral. Dehydration can result.

[0007] Gastrointestinal inflammation is associated with inflammation involving the gastrointestinal tract. Similarly, it can be inflammation of the upper or lower gastrointestinal tract. Examples of gastrointestinal inflammation include enterocolitis, NEC (necrotizing enterocolitis), and esophagitis. As mentioned earlier, gastrointestinal infections can also be associated with gastrointestinal inflammation.

[0008] Enterocolitis is an inflammation of the digestive tract involving the small intestine and colon. Common clinical manifestations of enterocolitis include frequent diarrhea, with or without nausea, vomiting, abdominal pain, fever, chills, and changes in systemic symptoms. It is generally caused by the spread of an infectious agent or its toxins within the body, or most commonly by severe loss of water and minerals, ultimately leading to diarrhea and vomiting.

[0009] Necrotizing enterocolitis (NEC) is a medical condition primarily seen in preterm infants, in which part of the intestine undergoes necrosis (tissue death). It occurs after birth and is the second leading cause of death in preterm infants. Initial symptoms include feeding intolerance, increased gastric residue, abdominal distension, and bloody stools. Symptoms can rapidly progress to abdominal discoloration, accompanied by significant intestinal necrosis, intestinal perforation, peritonitis, systemic hypotension requiring extensive medical support, surgical intervention, and sometimes death.

[0010] Esophagitis is an inflammation of the esophagus. Clinical manifestations include pain, drooling, dysphagia, and / or dysphagia. Complications may include bleeding, iron deficiency, and / or stricture.

[0011] Gastrointestinal infections / inflammation can have bacterial, viral, fungal, parasitic, or any other source such as the environment.

[0012] Viruses (especially rotavirus), as well as species of Escherichia coli and Campylobacter, are the main causes of gastroenteritis. However, many other infectious agents can cause this syndrome, and occasionally non-infectious causes (such as environmental factors) are also found.

[0013] Rotavirus, norovirus, adenovirus, and astrovirus are known to cause viral gastroenteritis.

[0014] In developed countries, Campylobacter jejuni is a leading cause of bacterial gastroenteritis, with half of the cases related to contact with poultry. In children, bacterial causes account for approximately 15% of cases, with the most common types being Escherichia coli, Salmonella, Shigella, and Campylobacter species.

[0015] Many protozoa (parasites) can also cause gastroenteritis, the most common being Giardia lamblia, but also including Amoeba hemorrhagicum and species of Cryptosporidium. As a group, these pathogens account for about 10% of cases in children.

[0016] Enterocolitis can be similarly caused by a variety of infections resulting from bacteria, viruses, fungi, parasites, or other causes.

[0017] Toxins (e.g., from Clostridium difficile) can also cause intestinal infections / inflammation.

[0018] Infections / inflammation can also be caused by opportunistic pathogens, for example, in cases of ecological imbalance (such as after antibiotic treatment).

[0019] Gastrointestinal inflammation also has many non-infectious (e.g., environmental) causes. Some common non-infectious causes include medications (such as nonsteroidal anti-inflammatory drugs (NSAIDs)), certain foods such as lactose (for those who are intolerant) and gluten (for those with celiac disease). It can also occur secondary to contamination or Crohn's disease. Some commonly associated foods include raw or undercooked meat, poultry, seafood, eggs, raw bean sprouts, unpasteurized milk and soft cheese, fruit and vegetable juices, as well as ciguatera poisoning from contaminated carnivorous fish, mackerel poisoning associated with certain types of spoiled fish, tetrodotoxin poisoning from consuming pufferfish, and botulism, usually caused by improper food storage.

[0020] In infants and young children, the source of esophagitis may be digestive (caused by acid reflux), but other sources have also been described, such as corrosive, radiation-induced, post-infection, drug-induced (antibiotics, NSAIDs, etc.), or inflammatory (such as Crohn's disease).

[0021] Breastfeeding is recommended for all infants. However, in some cases, due to medical reasons, breastfeeding is insufficient or unsuccessful, or the mother does not choose to breastfeed. Infant formula has been developed to address these situations. Fortifiers, which enrich breast milk or infant formula with special ingredients, have also been developed.

[0022] Therefore, especially for infants and young children who cannot be continuously breastfed, there is a need to establish nutritional solutions that will help protect them from intestinal inflammation / infection, especially those caused by true pathogens and opportunistic pathogens.

[0023] In specific cases, one possible solution is, for example, directly targeting the pathogen with antibiotics. However, in most cases of gastrointestinal infections / inflammation, this approach can be detrimental because the symbiotic microbiota, which are key contributors to defense through a mechanism known as colonization resistance, is also affected by the treatment. Furthermore, this antibiotic treatment will be ineffective against viral infections. Bacterial resistance to antibiotic treatment is also a significant issue.

[0024] Therefore, alternative approaches are clearly needed to reduce the incidence of these painful and potentially serious health conditions in infants and young children.

[0025] Numerous attempts have been made to develop alternative ways to prevent / treat intestinal infections and / or inflammation. Scientists have focused on the use of probiotics. Probiotics are considered viable microbial preparations that enhance individual health by maintaining the natural gut microbiota. We believe that probiotics attach to the intestinal mucosa, colonize the gut, and prevent harmful microorganisms from attaching to it. For probiotics to be effective, a prerequisite is that they must reach the intestinal mucosa in an appropriate, viable form without being destroyed in the upper gastrointestinal tract, especially unaffected by the generally low pH of the stomach.

[0026] For example, WO2004001022, published by the University of Newcastle Research, provides a method for treating health conditions such as gastrointestinal diseases using Propionibacterium jensenii strain 702.

[0027] In addition to probiotics, other pathways have been explored, such as the use of prebiotics, especially human milk oligosaccharides (HMOs). All human milk oligosaccharides (HMOs) are the third largest solid component in human milk after lactose and fat. HMOs typically contain lactose at the reducing end and a carbohydrate core at the non-reducing end, which usually contains fucose or sialic acid. More than one hundred HMOs have been isolated and characterized in human milk.

[0028] Therefore, in response to different requirements, several compositions have been developed in the art using HMO components (such as fucoidylated oligosaccharides, lactose-N-tetrasaccharides, and lactose-N-neotetrasaccharides) for different purposes.

[0029] For example, WO2005055944, published by Children's Hospital Medical Center, describes a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a molecule containing a fucosylate in an α-2, α-3, or α-4 bond to a galactosyl group. Various molecules are described, such as 2'-fucosylate. This application is intended for the prevention or treatment of a wide range of infections, including intestinal infections, and is not specialized (in infants, children, or adults).

[0030] WO2004002495 describes oligosaccharide-containing substances or receptors bonded to diarrheal Escherichia coli and / or zoonotic Helicobacter pylori, and their use in, for example, pharmaceutical compositions, nutritional compositions, and other compositions for the prevention and treatment of diarrhea, hemorrhagic colitis, or hemolytic uremic syndrome.

[0031] Abbott's publication WO9956754 relates to compositions containing at least one fucose residue, such as 2FL, at the α1-2 bond and their uses. Specifically, such compositions can be used to treat and prevent gastrointestinal infections, such as diarrhea and enterocolitis.

[0032] US2014248415 describes several examples of HMO mixtures, some of which involve different proportions of 2FL and LNnT. They can be used for a variety of health benefits, such as immune system maturation, allergic reactions, influenza, and diarrhea.

[0033] As disclosed in Abbott's WO9843494, oligosaccharides are known to have protective effects against respiratory, gastrointestinal, genitourinary, and reproductive tract infections. Several examples of HMOs, individually or in combination, are provided, without associating a specific type of oligosaccharide or its synergistic effects with any particular benefit.

[0034] However, most existing technical literature suggests that compositions containing multiple concentrations of different types of HMOs may not be particularly suitable for the needs of infants (e.g., their concentrations are very different from those found in breast milk).

[0035] Abbott's WO9843495 discloses a method for inhibiting infection of an individual with Bacteroides, Clostridium, and Escherichia coli, comprising feeding the individual with a synthetic nutrient formulation containing an effective amount of lactose-N-neotetrasaccharide. By inhibiting the growth of these bacteria, the infant is provided with resistance to gastroenteritis.

[0036] Further research has focused particularly on the various relationships between HMOs and probiotic strains.

[0037] For example, Nestec SA's WO2009077352 relates to a composition for preventing opportunistic infections in immunocompromised individuals, comprising Bifidobacterium and fucoidylated oligosaccharides. Opportunistic infections can be respiratory, urinary, or gastrointestinal infections.

[0038] Nestec SA's WO2009112361 discloses a formulation containing N-acetyl-lactoside and / or oligosaccharides containing N-acetyl-lactoside and probiotic Lactobacillus species, and the use of the formulation for the prevention and treatment of pathogenic infections of the gastrointestinal tract and upper respiratory tract.

[0039] Therefore, most existing technical literature deals with compositions applicable to various health conditions located in different parts of the body (respiratory tract, urinary tract, intestines, etc.), so they are not necessarily focused on or particularly suitable for gastrointestinal infections / inflammation. Others only address bacterial infections, and it is conceivable that the proposed nutritional solutions will be ineffective against other types of infections due to their direct targeting of the responsible bacteria.

[0040] Therefore, there is a need to develop nutritional compositions that are particularly effective and suitable for the prevention or treatment of gastrointestinal infections / inflammation, regardless of their source (bacteria, viruses, fungi, parasites, environment or any other source), and that are also effective against a variety of intestinal conditions (enteritis, gastroenteritis, infectious diarrhea, enterocolitis, NEC, esophagitis).

[0041] It is clear that appropriate methods need to be developed to reduce the incidence of these health conditions in infants and young children.

[0042] Because these infants or toddlers are particularly vulnerable, there is a need for ways to deliver these health benefits in a manner that is particularly suitable for these young subjects (infants and toddlers) and does not involve traditional drug interventions.

[0043] In addition, there is a need to deliver such health benefits to these infants or young children in a way that does not cause side effects and / or is not only easy to deliver but also widely accepted by parents or healthcare professionals.

[0044] Furthermore, there is a demand for such beneficial methods of delivery that are reasonably priced and affordable for most people.

[0045] Therefore, it is clear that there is a need to develop alternatives to traditional drug interventions (such as antibiotic use), for at least the aforementioned problem of resistance development.

[0046] There is also a need to develop alternative treatment pathways that are effective for a wide range of sources, i.e., etiologies independent of infection and / or inflammation (e.g., bacteria, viruses, fungi, parasites, environment, or any other source). Summary of the Invention

[0047] The inventors have discovered that compositions comprising at least one fucoidylated oligosaccharide and at least one specific N-acetylated oligosaccharide in specific proportions can be advantageously used to combat intestinal infections and / or inflammations in infants or young children, such as enteritis (including gastroenteritis), infectious diarrhea, enterocolitis, NEC, and esophagitis. Without being bound by theory, these oligosaccharides are believed to work synergistically to treat or prevent these specific health conditions.

[0048] Therefore, the present invention provides a nutritional composition comprising at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, the nutritional composition being used for the prevention and / or treatment of gastrointestinal infections and / or gastrointestinal inflammation in infants or young children, wherein...

[0049] - The ratio of fucoidylated oligosaccharides to N-acetylated oligosaccharides is 1:2 to 6.7:1;

[0050] - The total amount of fucoidylated oligosaccharides in the composition is from 0.5 g / L to 2 g / L, and / or, on a dry weight basis, the total amount of fucoidylated oligosaccharides in the composition is from 0.34 g / 100 g to 1.4 g / 100 g; and

[0051] - N-acetylated oligosaccharides are selected from the list of the following: lactose-N-tetrasaccharide (LNT), lactose-N-neotetrasaccharide (LNnT), para-lactose-N-neohexose (para-LNnH), lactose-N-hexose, lactose-N-neohexose, para-lactose-N-hexose, para-lactose-N-neohexose, lactose-N-octasaccharide, lactose-N-neooctasaccharide, isol-lactose-N-octasaccharide, para-lactose-N-octasaccharide, and lactose-N-decasaccharide or any combination thereof.

[0052] In some embodiments, the ratio of fucoidylated oligosaccharide to N-acetylated oligosaccharide is 1:1.5 to 4:1, such as 1:1 to 3:1, preferably 1.5:1 to 2.5:1, such as 2:1 or about 2:1. Therefore, in some embodiments, this ratio may be 1:1 to 2:1 or 1.5:1 to 2:1.

[0053] In a particularly advantageous embodiment, the nutritional composition comprises 2'-fucosyllactose (2-FL) and lactose-N-neotetrasaccharide (LNnT), and in particular, the amount of 2'-fucosyllactose (2-FL) in the nutritional composition is from 1 g / L to 1.5 g / L and the amount of LNnT in the nutritional composition is from 0.5 g / L to 0.7 g / L. Attached Figure Description

[0054] Figure 1This indicates the number of infants who experienced at least one gastrointestinal infection event in either the standard infant formula (control group) or the standard infant formula supplemented with 1.24 g / L 2'-fucosylated lactose and 0.63 g / L lactose-N-neotetrasaccharide (HMO group). Odds ratio (OR) = 0.5, p = 0.08. Control group n = 87, HMO group n = 88. Data were collected from infants aged 0 to 12 months.

[0055] Figure 2 This represents the percentage of infants without enteritis as time progresses between feeding standard infant formula (control group) and feeding standard infant formula supplemented with 1.24 g / L 2'-fucosylated lactose and 0.63 g / L lactose-N-neotetrasaccharide (HMO group). Control group n=87, HMO group n=88. Detailed Implementation

[0056] As used herein, the following terms have the following meanings.

[0057] The term "infant" refers to a child under 12 months of age.

[0058] The term "preschooler" refers to children aged between one and three years old, also known as toddlers.

[0059] "Cesarean section baby or toddler" refers to a baby or toddler delivered via cesarean section. This means that the baby or toddler was not delivered vaginally.

[0060] "Vaginal delivery infants or toddlers" refers to infants or toddlers delivered vaginally rather than via cesarean section.

[0061] Premature infants are babies or toddlers born before full term. This typically refers to infants or toddlers born before 36 weeks of gestation.

[0062] The term "nutritional composition" refers to a composition that supplies nutrients to an individual. Such nutritional compositions are typically administered orally or intravenously, and usually include lipid or fat sources as well as protein sources.

[0063] In one specific embodiment, the composition of the present invention is a hypoallergenic nutritional composition. The term "hypoallergenic nutritional composition" refers to a nutritional composition that is unlikely to cause an allergic reaction.

[0064] In one specific embodiment, the composition of the present invention is a "synthetic nutritional composition". The term "synthetic nutritional composition" refers to a mixture produced by chemical and / or biological methods, the chemical properties of which may be the same as those of mixtures naturally present in mammalian milk (i.e., the synthetic composition is not breast milk).

[0065] As used herein, the term "infant formula" refers to foods specifically designed to provide nutrition for infants in the first few months of life and which meet the diverse nutritional needs of this population (in accordance with Article 2(c) of European Commission Directive 91 / 321 / EEC 2006 / 141 / EC of 22 December 2006 concerning infant formula and follow-on formula). It also includes nutritional compositions intended for use in infants, as defined in the Codex Alimentarius Commission (STAN 72-1981) and for infant-specific products (including foods for specific medical purposes). The term "infant formula" encompasses both "Stage 1 infant formula" and "follow-up formula" or "Stage 2 infant formula."

[0066] "Follow-up formula" or "Stage 2 formula" is offered starting from the 6th month. Infant formula constitutes the main liquid element in the gradually diversifying diet of this group.

[0067] The term "infant food" refers to food specifically designed to provide nutrition for infants or toddlers under one year old.

[0068] The term "infant cereal composition" refers to food specifically designed to provide nutrition for infants or toddlers under one year of age.

[0069] The term "fortifier" refers to a liquid or solid nutritional composition suitable for mixing with breast milk or infant formula.

[0070] The term "weaning period" refers to the period during which breast milk is gradually replaced by other foods in the diet of infants or young children.

[0071] The expressions "age in days / weeks / months / age" and "number of days / weeks / months / years of birth" can be used interchangeably.

[0072] The terms "gastrointestinal tract," "GI tract," "GIT," "intestinal tract," and "GUT" are used interchangeably. This tract consists of the stomach and intestines, and is divided into the upper and lower gastrointestinal tracts. It refers to the system (including digestive organs) responsible for consuming and digesting food, absorbing nutrients, and eliminating waste. The GI tract specifically includes all digestive structures between the mouth and anus.

[0073] The upper gastrointestinal tract typically includes the esophagus and stomach. The lower gastrointestinal tract typically includes the small intestine and the entire large intestine (colon).

[0074] The terms "gastrointestinal infection / inflammation", "gastrointestinal infection and / or inflammation" and "gastrointestinal infection and / or gastrointestinal inflammation" are used interchangeably.

[0075] The phrase "prevention and / or treatment of gastrointestinal infections and / or gastrointestinal inflammation" includes one or more of the following:

[0076] - Prevention of gastrointestinal infections, i.e., intestinal infections

[0077] - Prevention of gastrointestinal inflammation, i.e., intestinal inflammation

[0078] - Treatment of gastrointestinal infections, i.e., intestinal infections

[0079] - Treatment of gastrointestinal inflammation, i.e., intestinal inflammation

[0080] The terms "gastrointestinal infection," "infection of the gastrointestinal tract," "intestinal infection," or "intestinal infection" are used interchangeably. These are illnesses caused by acute infections involving the gastrointestinal tract. Infections may be of the upper gastrointestinal tract, such as the esophagus and / or stomach. Infections may be of the lower gastrointestinal tract, such as the small intestine and all of the large intestine (colon). Examples of gastrointestinal infections include enteritis, gastroenteritis, infectious diarrhea, or combinations thereof. Intestinal infections may also be associated with intestinal inflammation, especially in cases of enteritis, gastroenteritis, and infectious diarrhea. Intestinal infections can have bacterial, viral, fungal, parasitic, environmental, or any other origin, as detailed above.

[0081] The terms "gastrointestinal inflammation," "inflammation of the gastrointestinal tract," "intestinal inflammation," or "inflammation of the intestines" are used interchangeably. They relate to inflammation involving the gastrointestinal tract. This could be inflammation of the upper gastrointestinal tract, such as the esophagus and / or stomach. It could be inflammation of the lower gastrointestinal tract, such as the small intestine and all of the large intestine (colon). Examples of gastrointestinal inflammation include enterocolitis, NEC (necrotizing enterocolitis), esophagitis, or combinations thereof. As mentioned earlier, gastrointestinal infections can also be associated with gastrointestinal inflammation.

[0082] The phrases “prevention of gastrointestinal infections and / or gastrointestinal inflammation”, “in order to prevent gastrointestinal infections and / or gastrointestinal inflammation”, “in the process of preventing gastrointestinal infections and / or gastrointestinal inflammation”, and “used for the prevention of gastrointestinal infections and / or gastrointestinal inflammation” are interchangeable.

[0083] These expressions refer to the avoidance of intestinal infections and / or inflammation and / or a reduction in the incidence (reduction in frequency, i.e., the number of intestinal infections and / or intestinal inflammations) of said infections and / or inflammations. In some embodiments, prevention of intestinal infections and / or intestinal inflammations occurs during treatment (i.e., during the administration of the compositions of the invention, or immediately after the start of administration, or some time after the start of administration, such as a few days or weeks after the start of administration). Prevention of intestinal infections and / or intestinal inflammations in later life may also be covered. The expression "in later life" covers the effect after the intervention or treatment has ended. This effect "in later life" may last from one week to several months, for example, two to four weeks, two to six weeks, two to eight weeks, one to six months, or two to twelve months.

[0084] The phrases "in the treatment of gastrointestinal infections and / or gastrointestinal inflammation", "for the treatment of gastrointestinal infections and / or gastrointestinal inflammation", "in the course of the treatment of gastrointestinal infections and / or gastrointestinal inflammation", and "for the treatment of gastrointestinal infections and / or gastrointestinal inflammation" are used interchangeably.

[0085] These statements should be understood to include shortening the duration of intestinal infection and / or intestinal inflammation (the number of days / weeks / years the infant or young child will suffer from intestinal infection and / or intestinal inflammation) and reducing the severity of intestinal infection and / or intestinal inflammation (the consequences and / or severity of intestinal infection and / or intestinal inflammation). These statements also cover the reduction of symptoms such as diarrhea, vomiting, abdominal pain, feeding difficulties / intolerance, irritability, poor sleep quality, fatigue, headache, fever, cramps, difficulty feeding, increased stomach contents, bloating, drooling, painful swallowing, difficulty swallowing, bloody stools, or combinations thereof, and / or reducing complications affecting the health of the infant or young child caused by intestinal infection and / or intestinal inflammation, such as dehydration, abdominal discoloration, intestinal perforation, peritonitis, intestinal necrosis, bleeding, iron deficiency, stricture, need for surgical intervention, need for extensive medical support, death, and / or reducing pain, and / or reducing fatigue, and / or making sleep comfortable, and / or calming the irritability of the infant or young child suffering from intestinal infection and / or intestinal inflammation.

[0086] "Breast milk" should be understood as the mother's milk or colostrum.

[0087] "Oligosaccharides" are carbohydrate polymers containing small amounts (usually three to ten parts) of simple sugars (monosaccharides).

[0088] The term "HMO" refers to human milk oligosaccharides. These carbohydrates are highly resistant to enzymatic hydrolysis, suggesting that their important functions may not be directly related to their calorific value. It has been specifically noted in the art that these carbohydrates play a crucial role in early infant and toddler development, such as in the maturation of the immune system. Many different types of HMOs have been found in human milk. The structure of each individual oligosaccharide is based on a variety of combinations of glucose, galactose, sialic acid (N-acetylneuraminic acid), fucose, and / or N-acetylglucosamine with these molecules, resulting in a large number of diverse oligosaccharides in human milk; more than 130 such structures have been identified to date. Almost all oligosaccharides have a lactose molecule at the reducing end, and the non-reducing terminal positions are occupied by sialic acid and / or fucose (if present). HMOs can be acidic (e.g., oligosaccharides containing charged sialic acid) or neutral (e.g., fucoidylated oligosaccharides).

[0089] "Fucosylated oligosaccharides" are oligosaccharides containing fucose residues. These oligosaccharides are neutral. Some examples are 2-FL (2'-fucosyllactose), 3-FL (3-fucosyllactose), difucosyllactose, lactose-N-fucopentose (e.g., lactose-N-fucopentose I, lactose-N-fucopentose II, lactose-N-fucopentose III, lactose-N-fucopentose V), lactose-N-fucohexose, lactose-N-difucohexose I, fucosyllactose-N-hexose, fucosyllactose-N-neohexose, difucosyllactose-N-hexose I, difucosyllactose-N-neohexose II, and any combination thereof. While not wishing to be bound by theory, it is believed that the fucosyl epitope of fucosylated oligosaccharides can act as a "decoy" at mucosal surfaces. This epitope can utilize a competitive effect to prevent and / or limit the action of infectious pathogens (viral or bacterial in origin) or pathogen-secreted components (such as toxins), particularly by preventing the pathogen or its secreted components from binding to natural ligands, and is not bound by theory, thus believed to reduce the risk of intestinal infection / inflammation. Furthermore, it is thought that fucosylated oligosaccharides can promote the growth and metabolic activity of specific symbiotic microbiota, reduce inflammatory responses, and create an environment unfavorable to pathogens, thereby leading to colonization resistance.

[0090] The terms "fucosylated oligosaccharides containing a 2'-fucosylation epitope" and "2-fucosylated oligosaccharides" encompass a range of homologous fucosylated oligosaccharides that all contain a 2'-fucosylation epitope, suggesting a possible homologous function. Without being bound by theory, it is believed that the 2'-fucosylation epitope of these fucosylated oligosaccharides is specifically targeted at pathogens (or their secreted components) associated with intestinal infections.

[0091] The term "N-acetylated oligosaccharide" encompasses both "N-acetyl-lactoside" and "oligosaccharide containing N-acetyl-lactoside." This oligosaccharide is a neutral oligosaccharide containing N-acetyl-lactoside residues. In this invention, the N-acetylated oligosaccharide is selected from the list of the following: LNT (lactose-N-tetrasaccharide), para-lactose-N-neohexose (para-LNnH), LNnT (lactose-N-neohexose), lactose-N-hexose, lactose-N-neohexose, para-lactose-N-hexose, para-lactose-N-neohexose, lactose-N-octasose, lactose-N-neohexose, isol-lactose-N-octasose, para-lactose-N-octasose, and lactose-N-decanose or any combination thereof. Unbound by theory, these oligosaccharides are believed to exert synergistic protective effects by binding with fucosylated oligosaccharides because they (i) target a variety of adhesins and quorum sensing mechanisms of pathogens, thereby reducing their virulence and competitiveness, and (ii) facilitate the establishment, competitiveness, and metabolic activities of symbiotic microbiota, leading to colonization resistance.

[0092] The expressions “at least one fucoidylated oligosaccharide” and “at least one N-acetylated oligosaccharide” refer to “at least one type of fucoidylated oligosaccharide” and “at least one type of N-acetylated oligosaccharide”.

[0093] The expressions “ratio of fucoidan to N-acetylated oligosaccharides,” “ratio of fucoidan to N-acetylated oligosaccharides,” and “ratio between fucoidan and N-acetylated oligosaccharides” are used interchangeably. They refer to the weight ratio between the total amount of fucoidan (i.e., all) and the total amount of N-acetylated oligosaccharides (i.e., all).

[0094] "HMO precursors" are key compounds that intervene in HMO production, such as sialic acid and / or fucose.

[0095] "Sialinated oligosaccharides" are oligosaccharides containing charged sialic acid, that is, oligosaccharides containing sialic acid residues. These oligosaccharides are acidic. Some examples are 3-SL (3'-sialyl-lactose) and 6-SL (6'-sialyl-lactose).

[0096] The nutritional compositions of the present invention may be in solid form (e.g., powder) or liquid form. The amounts of various ingredients (e.g., oligosaccharides) may be expressed as g / 100g composition on dry weight when the composition is in solid form (e.g., powder); or as concentration g / L composition when the composition is in liquid form (the latter also covers liquid compositions that can be obtained by reconstituted powder with liquids such as milk, water, etc., such as reconstituted infant formula or stage 2 / follow-up formula, or infant cereal products, or any other infant formula specifically designed for infant nutrition).

[0097] The term "prebiotic" refers to non-digestible carbohydrates that produce beneficial effects on the host by selectively stimulating the growth and / or activity of healthy bacteria such as Bifidobacteria in the human colon (Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995; 125:1401-12).

[0098] The term "probiotics" refers to microbial cell preparations or microbial cell components that have beneficial effects on the health or well-being of the host. (Salminen S, Ouwehand A. Benno Y. et al., "Probiotics: how should they be defined?" Trends Food Sci. Technol. 1999:10 107-10). The microbial cells are generally bacteria or yeast.

[0099] The term "cfu" should be understood as colony-forming unit.

[0100] Unless otherwise specified, all percentages are by weight.

[0101] Furthermore, in the context of this invention, the terms "comprising" or "including" do not exclude other possible elements. The compositions of this invention, including the various embodiments described herein, may comprise, be composed of, or substantially consist of the following elements: the essential elements and limitations described herein, and any other or optional ingredients, components, or limitations described herein, or as required.

[0102] Any references to prior art documents in this specification should not be construed as an admission that such prior art is well-known or constitutes part of common general knowledge in the art.

[0103] The invention will now be described in more detail. It should be noted that the various aspects, features, embodiments, and implementations described in this application may be compatible and / or can be combined together.

[0104] Therefore, the primary objective of this invention is a nutritional composition comprising at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, for the prevention and / or treatment of gastrointestinal infections and / or gastrointestinal inflammation in infants or young children, wherein:

[0105] - The ratio of fucoidylated oligosaccharides to N-acetylated oligosaccharides is 1:2 to 6.7:1;

[0106] - The total amount of fucoidylated oligosaccharides in the composition is from 0.5 g / L to 2 g / L, and / or, on a dry weight basis, the total amount of fucoidylated oligosaccharides in the composition is from 0.34 g / 100 g to 1.4 g / 100 g; and

[0107] - N-acetylated oligosaccharides are selected from the list of the following: lactose-N-tetrasaccharide (LNT), lactose-N-neotetrasaccharide (LNnT), para-lactose-N-neohexose (para-LNnH), lactose-N-hexose, lactose-N-neohexose, para-lactose-N-hexose, para-lactose-N-neohexose, lactose-N-octasaccharide, lactose-N-neooctasaccharide, isol-lactose-N-octasaccharide, para-lactose-N-octasaccharide, and lactose-N-decasaccharide or any combination thereof.

[0108] Unbound by theory, the oligosaccharides in the nutritional compositions of this invention can function at different levels to support the natural defenses of developing infants or young children: (i) promoting symbiotic microbiota for better colonization resistance, (ii) enhancing innate immunity against pathogens, and / or (iii) acting directly as decoys against pathogens, causing them to dissociate from their natural targets. It is also believed that, for these purposes, fucosylated oligosaccharides synergize with specific N-acetylated oligosaccharides. They exert synergistic protective effects because they target a wide variety of adhesins and quorum sensing mechanisms of pathogens, thereby reducing their virulence and competitiveness, and they promote the establishment and competitiveness of symbiotic microbiota and metabolic activity, leading to colonization resistance.

[0109] The compositions of the present invention comprise at least one fucoidan. One or more types of fucoidan may be present. The fucoidan may be substantially selected from the list including: 2'-fucosylvose, 3'-fucosylvose, difucosylvose, lactose-N-fucopentose (such as lactose-N-fucopentose I, lactose-N-fucopentose II, lactose-N-fucopentose III, lactose-N-fucopentose V), lactose-N-fucohexose, lactose-N-difucohexose I, fucoidan-N-hexose, etc. Fucosyl lactose-N-neohexoses (such as fucosyl lactose-N-neohexose I, fucosyl lactose-N-neohexose II), difucosyl lactose-N-hexose I, difucosyl-lactose-N-neohexose, difucosyl lactose-N-neohexose I, difucosyl lactose-N-neohexose II, fucosyl-para-lactose-N-hexose, trifucosyl-para-lactose-N-hexose I, and any combination thereof.

[0110] In some specific embodiments, the fucoidylated oligosaccharide contains a 2'-fucosylation epitope. Such fucoidylated oligosaccharide may, for example, be selected from the list including: 2'-fucosylation lactose, difucosylation lactose, lactose-N-fucopentose, lactose-N-fucohexose, lactose-N-difucohexose, fucosylation lactose-N-hexose, fucosylation lactose-N-neohexose, difucosylation lactose-N-hexose, difucosylation lactose-N-neohexose, difucosylation lactose-N-neohexose, fucosylation-para-lactose-N-hexose, and any combination thereof.

[0111] In a preferred embodiment, the nutritional composition according to the invention comprises 2'-fucosylated lactose (or 2FL, or 2'FL, or 2-FL or 2'-FL). In a specific embodiment, no other type of fucosylated oligosaccharide is present besides 2'-fucosylated lactose; that is, the nutritional composition of the invention comprises only 2'-fucosylated lactose as a fucosylated oligosaccharide.

[0112] Fucosylated oligosaccharides can be isolated from natural sources such as animal milk using chromatography or filtration techniques. Alternatively, they can be prepared using specialized fucosyltransferases and / or fucosidases via biotechnological means, employing enzyme-based fermentation techniques (recombinant or natural enzymes) or microbial fermentation. In the latter case, the microorganisms can express their natural enzymes and substrates, or can be engineered to produce the corresponding substrates and enzymes. Single microbial cultures and / or mixed cultures can be used. Fucosylated oligosaccharides can be formed starting with acceptor substrates initially having any degree of polymerization (DP), beginning with DP = 1. Alternatively, fucosylated oligosaccharides can be prepared by chemical synthesis from lactose and free fucose. Fucosylated oligosaccharides are also available, for example, from Kyowa Hakko Kogyo Co., Ltd. (Kyowa, Hakko, Kogyo, Japan).

[0113] The compositions of the present invention further comprise at least one N-acetylated oligosaccharide selected from the list of the following compositions: lactose-N-tetrasaccharide (LNT), lactose-N-neotetrasaccharide (LNnT), p-lactose-N-neohexose (p-LNnH), lactose-N-hexose, lactose-N-neohexose, p-lactose-N-hexose, p-lactose-N-neohexose, lactose-N-octasaccharide, lactose-N-neohexose, isolose-N-octasaccharide, p-lactose-N-octasaccharide, and lactose-N-decasaccharide, or any combination thereof. One or more types of N-acetylated oligosaccharides may be present. The N-acetylated oligosaccharide may be, for example, lactose-N-tetrasaccharide (LNT), lactose-N-neotetrasaccharide (LNnT), or any combination thereof. In some embodiments, the N-acetylated oligosaccharide is lactose-N-neotetrasaccharide (LNnT), p-lactose-N-neohexose (p-LNnH), or any combination thereof. In some embodiments, the N-acetylated oligosaccharide is LNnT. In some embodiments, the N-acetylated oligosaccharide is LNT. In some other embodiments, the N-acetylated oligosaccharide is a mixture of LNT and LNnT. In some embodiments, the composition of the present invention comprises both LNT and LNnT, wherein the LNT:LNnT ratio is between 5:1 and 1:2, or from 2:1 to 1:1, or from 2:1.2 to 2:1.6.

[0114] In a preferred embodiment, the nutritional composition according to the invention comprises lactose-N-neotetrasaccharide (LNnT). In a specific embodiment, no other type of N-acetylated oligosaccharide is contained other than lactose-N-neotetrasaccharide (LNnT), i.e., the nutritional composition of the invention contains only lactose-N-neotetrasaccharide (LNnT) as an N-acetylated oligosaccharide.

[0115] N-acetylated oligosaccharides can be chemically synthesized using enzymatic transfer methods, whereby glycosyltransferases are used to transfer sugar units from the donor moiety to the acceptor moiety, as described, for example, in U.S. Patents 5,288,637 and WO 96 / 10086. Alternatively, LNT and LNnT can be prepared by chemically converting free or oligosaccharide-bound ketohexoses (e.g., fructose) into N-acetylated hexosamine or oligosaccharides containing N-acetylated hexosamine, as described in Wrodnigg, TM; Stutz, AE (1999) Angew. Chem. Int. Ed. 38:827-828. The N-acetylated lactoside obtained in this manner can then be transferred to lactose, which serves as the acceptor moiety.

[0116] In a particularly advantageous embodiment of the invention, the nutritional composition comprises 2'-fucosylated lactose (2FL) and lactose-N-neotetrasaccharide (LNnT).

[0117] In another specific embodiment, the nutritional composition of the present invention comprises a mixture of oligosaccharides consisting of 2'-fucosylated lactose (2-FL) and lactose-N-neotetrasaccharide (LNnT). In other words, the nutritional composition of the present invention contains only 2'-fucosylated lactose (2-FL) as a fucosylated oligosaccharide and only lactose-N-neotetrasaccharide (LNnT) as an N-acetylated oligosaccharide.

[0118] In this invention, fucoidan and N-acetylated oligosaccharides are present in the nutrient composition in a specific ratio. The ratio of fucoidan to N-acetylated oligosaccharides is from 1:2 to 6.7:1, preferably from 1:1.5 to 4:1, such as from 1:1 to 3:1 or from 1.5:1 to 2.5:1. In a particularly advantageous embodiment, the ratio is 2:1 or about 2:1.

[0119] Fucosylated oligosaccharides and N-acetylated oligosaccharides may be present in specific amounts in a nutritional composition. Unless otherwise specified, the term "amount" refers to the total amount of each of these components in the nutritional composition. Therefore, it does not refer to the individual amount unless a single type of these components is present (in which case the total amount and the individual amount are equal). As an exemplary example, if only one type of fucosylated oligosaccharide (e.g., 2FL) is present in the composition, its individual amount (and therefore also the total amount of fucosylated oligosaccharides) will be in the range of 0.5 g / L to 2 g / L. If several types of fucosylated oligosaccharides are present, their individual amount will decrease (e.g., if two different types of fucosylated oligosaccharides are present, such as 2FL + 3FL, the individual amount may be, for example, 0.5 g / L each), but the total amount of fucosylated oligosaccharides will be in the range of 0.5 g / L to 2 g / L.

[0120] The total amount of fucoidan-based oligosaccharides in the nutritional composition according to the invention is from 0.5 g / L to 2 g / L. In some embodiments, the total amount of fucoidan-based oligosaccharides in the nutritional composition according to the invention may be from 0.75 g / L to 1.65 g / L. In some embodiments, the total amount of fucoidan-based oligosaccharides may be 0.8-1.5 g / L, such as 0.85-1.3 g / L, or 0.9-1.25 g / L, or 0.9-1.1 g / L, or 1-1.25 g / L, or 1.05-1.25 g / L. In one specific embodiment, the total amount of fucoidan-based oligosaccharides is 1 g / L. In another specific embodiment, the total amount of fucoidan-based oligosaccharides is 1.24 g / L.

[0121] The total amount of fucoidan-based oligosaccharides in the nutritional composition according to the invention, based on dry weight, is from 0.34 g / 100 g to 1.4 g / 100 g of the composition. In some embodiments, the total amount of fucoidan-based oligosaccharides in the nutritional composition, based on dry weight, may be from 0.52 g / 100 g to 1.15 g / 100 g of the composition. The total amount of fucoidan-based oligosaccharides may be 0.55-1.05 g / 100 g of the composition, such as 0.59-0.9 g / 100 g of the composition, or 0.62-0.87 g / 100 g of the composition, or 0.62-0.77 g / 100 g of the composition, or 0.69-0.87 g / 100 g of the composition, or 0.73-0.87 g / 100 g of the composition. In one specific embodiment, the total amount of fucoidan-based oligosaccharides is 0.69 g / 100 g of the composition. In another specific embodiment, the total amount of fucoidylated oligosaccharides is 0.86 g / 100 g of the composition.

[0122] The total amount of N-acetylated oligosaccharides present in the nutritional composition according to the invention may be from 0.3 g / L to 1 g / L of the composition, such as from 0.45 g / L to 0.85 g / L of the composition.

[0123] In some embodiments, the total amount of N-acetylated oligosaccharides may be 0.5-0.8 g / L of the composition, such as 0.5-0.75 g / L or 0.5-0.7 g / L. In one specific embodiment, the total amount of N-acetylated oligosaccharides is 0.5 g / L of the composition. In another specific embodiment, the total amount of N-acetylated oligosaccharides is 0.63 g / L of the composition.

[0124] The total amount of N-acetylated oligosaccharides in the nutritional composition, on a dry weight basis, can be from 0.2 g / 100 g to 0.7 g / 100 g of the composition, such as 0.31 g / 100 g to 0.59 g / 100 g of the composition on a dry weight basis. The total amount of N-acetylated oligosaccharides can be from 0.35 g / 100 g to 0.56 g / 100 g of the composition, such as 0.35 g / 100 g to 0.52 g / 100 g or 0.35 g / 100 g to 0.49 g / 100 g. In one specific embodiment, the total amount of N-acetylated oligosaccharides is 0.35 g / 100 g of the composition. In another specific embodiment, the total amount of N-acetylated oligosaccharides is 0.44 g / 100 g of the composition.

[0125] Therefore, in one embodiment of the present invention, the nutritional composition comprises at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, wherein:

[0126] - The total amount of fucoidylated oligosaccharides in the composition is from 0.5 g / L to 2 g / L, and / or, on a dry weight basis, the total amount of fucoidylated oligosaccharides in the composition is from 0.34 g / 100 g to 1.4 g / 100 g; and

[0127] - The total amount of N-acetylated oligosaccharides is 0.3 g / L to 1 g / L of the composition, such as, and / or the total amount of N-acetylated oligosaccharides is 0.2 g / 100 g to 0.7 g / 100 g of the composition on a dry weight basis.

[0128] In another embodiment of the invention, the nutritional composition comprises at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, wherein:

[0129] - The total amount of fucoidylated oligosaccharides in the composition is from 0.75 g / L to 1.65 g / L, and / or, on a dry weight basis, the total amount of fucoidylated oligosaccharides in the composition is from 0.52 g / 100 g to 1.15 g / 100 g; and / or

[0130] - The total amount of N-acetylated oligosaccharides is from 0.45 g / L to 0.85 g / L of the composition, and / or the total amount of N-acetylated oligosaccharides is from 0.31 g / 100 g to 0.59 g / 100 g of the composition on a dry weight basis.

[0131] In another embodiment of the invention, the nutritional composition comprises at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, wherein:

[0132] - The total amount of fucoidylated oligosaccharides in the composition is from 0.8 g / L to 1.5 g / L, and / or, on a dry weight basis, the total amount of fucoidylated oligosaccharides in the composition is from 0.55 g / 100 g to 1.05 g / 100 g; and / or

[0133] - The total amount of N-acetylated oligosaccharides is 0.5 g / L to 0.8 g / L of the composition, and / or the total amount of N-acetylated oligosaccharides is 0.35 g / 100 g to 0.56 g / 100 g of the composition on a dry weight basis.

[0134] In another specific embodiment, the nutritional composition of the present invention comprises at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, wherein:

[0135] - The total amount of fucoidylated oligosaccharides in the composition is from 0.85 g / L to 1.3 g / L, and / or, on a dry weight basis, the total amount of fucoidylated oligosaccharides in the composition is from 0.59 g / 100 g to 0.9 g / 100 g; and / or

[0136] - The total amount of N-acetylated oligosaccharides is 0.5 g / L to 0.75 g / L of the composition, and / or the total amount of N-acetylated oligosaccharides is 0.35 g / 100 g to 0.52 g / 100 g of the composition on a dry weight basis.

[0137] In another specific embodiment, the nutritional composition of the present invention comprises at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, wherein:

[0138] - The total amount of fucoidylated oligosaccharides in the composition is from 1 g / L to 1.25 g / L, and / or the total amount of fucoidylated oligosaccharides in the composition is from 0.69 g / 100 g to 0.87 g / 100 g on a dry weight basis; and / or

[0139] - The total amount of N-acetylated oligosaccharides is 0.5 g / L to 0.7 g / L of the composition, and / or the total amount of N-acetylated oligosaccharides is 0.35 g / 100 g to 0.49 g / 100 g of the composition on a dry weight basis.

[0140] In another specific embodiment, the nutritional composition of the present invention comprises at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, wherein:

[0141] - The total amount of fucoidylated oligosaccharides in the composition is from 1.05 g / L to 1.25 g / L, and / or the total amount of fucoidylated oligosaccharides in the composition is from 0.73 g / 100 g to 0.87 g / 100 g on a dry weight basis; and / or

[0142] - The total amount of N-acetylated oligosaccharides is 0.5 g / L to 0.7 g / L of the composition, and / or the total amount of N-acetylated oligosaccharides is 0.35 g / 100 g to 0.49 g / 100 g of the composition on a dry weight basis.

[0143] In one specific embodiment, the nutritional composition according to the invention comprises at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, wherein:

[0144] - The total amount of fucoidylated oligosaccharides is 1 g / L of the composition, and / or, on a dry weight basis, the total amount of fucoidylated oligosaccharides is 0.69 g / 100 g of the composition; and / or

[0145] - The total amount of N-acetylated oligosaccharides is 0.5 g / L of the composition, and / or the total amount of N-acetylated oligosaccharides is 0.35 g / 100 g of the composition on a dry weight basis.

[0146] In another specific embodiment, the nutritional composition according to the invention comprises at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, wherein:

[0147] - The total amount of fucoidylated oligosaccharides in the composition is 1.24 g / L, and / or the total amount of fucoidylated oligosaccharides in the composition is 0.86 g / 100 g of the composition on a dry weight basis; and / or

[0148] - The total amount of N-acetylated oligosaccharides is 0.63 g / L of the composition, and / or the total amount of N-acetylated oligosaccharides is 0.44 g / 100 g of the composition on a dry weight basis.

[0149] The nutritional composition according to the invention may further comprise at least one additional oligosaccharide (i.e., in addition to fucoidylated oligosaccharides and N-acetylated oligosaccharides, which must be present in the composition) and / or at least one fiber and / or at least one precursor thereof. Other oligosaccharides and / or fibers and / or their precursors may be selected from the list comprising: galactooligosaccharides (GOS), fructooligosaccharides (FOS), inulin, xylooligosaccharides (XOS), polydextrose, sialylated oligosaccharides, sialic acid, fucose, and any combination thereof. Their amounts may be between 0% and 10% by weight of the composition.

[0150] In addition to the oligosaccharides contained in the oligosaccharide mixture, suitable commercial products for preparing the nutritional compositions according to the present invention include: combinations of FOS and inulin, such as products sold by BENEO under the trademark Orafti, or by Tate & Lyle under the trademark STA-LITE. ® Polydextrose for sale.

[0151] In one specific embodiment, the composition according to the invention may comprise sialylated oligosaccharides.

[0152] The sialylated oligosaccharide may be selected from the group consisting of 3'-sialyl lactose (3-SL), 6'-sialyl lactose (6-SL), and any combination thereof. In some embodiments of the invention, the composition comprises 3-SL and 6-SL. In some specific embodiments, the ratio of 3'-sialyl lactose (3-SL) to 6'-sialyl lactose (6-SL) may be between 5:1 and 1:10, or between 3:1 and 1:1, or within the range of 1:1 to 1:10.

[0153] In some specific embodiments, the sialylated oligosaccharide of the composition is 6'-sialyl lactose (6-SL).

[0154] Sialized oligosaccharides can be isolated from natural sources (such as animal milk) using chromatography or filtration techniques. Alternatively, sialylated oligosaccharides can be prepared using specialized sialyltransferases, sialidases, or sialylases via biotechnology, through enzyme-based fermentation (recombinant or natural enzymes), chemical synthesis, or microbial fermentation. In the latter case, the microorganisms can express their natural enzymes and substrates, or can be engineered to produce the corresponding substrates and enzymes. Single or mixed microbial cultures can be used. Sialized oligosaccharides can be formed starting with acceptor substrates initially having any degree of polymerization (DP), beginning with DP = 1. Alternatively, sialylated lactose can be prepared chemically from lactose and free N'-acetylneuraminic acid (sialic acid). Sialyllated lactose can also be commercially available, for example, from Kyowa HakkoKogyo Co., Ltd.

[0155] In specific examples, the composition may contain 0.05 g / L to 5 g / L of sialylated oligosaccharides, or 0.1 g / L to 4 g / L, or 0.3 g / L to 2 g / L, or 0.4 g / L to 1.5 g / L, or 0.4 g / L to 1 g / L, such as 0.5 g / L or 0.9 g / L of sialylated oligosaccharides. In some specific embodiments, the composition may contain 0.8 g / L to 1.7 g / L of sialylated oligosaccharides.

[0156] On a dry weight basis, the composition according to the invention may contain 0.03 g to 3.5 g of sialylated oligosaccharides per 100 g of the composition, for example 0.1 g to 2 g, or 0.2 g to 1 g, or 0.3 g to 0.6 g of sialylated oligosaccharides per 100 g of the composition.

[0157] In some specific embodiments of the invention, the nutritional composition contains sialylated oligosaccharides in an amount of less than 0.1 g / 100 g of composition, based on dry weight.

[0158] In some specific embodiments of the invention, the nutritional composition does not contain any sialylated oligosaccharides (GOS).

[0159] In one specific embodiment, the nutritional composition may also contain at least one BMO (milk oligosaccharide).

[0160] In another specific embodiment, the nutritional composition does not contain any milk oligosaccharides.

[0161] In another specific embodiment, the nutritional composition of the present invention does not contain any N-acetylgalactosamine and / or any galactosyl-N-acetylgalactosamine, that is, it contains no or only trace amounts (e.g., less than 0.03 g / 100 g of the nutritional composition on a dry weight basis, e.g., less than 0.005% by weight) of N-acetylgalactosamine and / or any galactosyl-N-acetylgalactosamine.

[0162] The compositions according to the invention may optionally contain at least one oligosaccharide precursor. One or more oligosaccharide precursors may be present. For example, human milk oligosaccharide precursors are sialic acid, fucose, or mixtures thereof. In some specific embodiments, the composition contains sialic acid.

[0163] In some specific examples, the composition comprises 0 g / L to 3 g / L of oligosaccharide precursor, or 0 g / L to 2 g / L of oligosaccharide precursor, or 0 g / L to 1 g / L of oligosaccharide precursor, or 0 g / L to 0.7 g / L of oligosaccharide precursor, or 0 g / L to 0.5 g / L of oligosaccharide precursor, or 0 g / L to 0.3 g / L of oligosaccharide precursor, or 0 g / L to 0.2 g / L of oligosaccharide precursor.

[0164] On a dry weight basis, the composition according to the invention may contain 0 g to 2.1 g of oligosaccharide precursor per 100 g of composition, for example 0 g to 1.5 g of oligosaccharide precursor, or 0 g to 0.8 g of oligosaccharide precursor, or 0 g to 0.15 g of oligosaccharide precursor per 100 g of composition.

[0165] The nutritional composition of the present invention may also contain at least one probiotic (or probiotic strain), such as a probiotic strain.

[0166] The most commonly used probiotic microorganisms are mainly bacteria and yeasts belonging to the following genera: Lactobacillus species, Streptococcus species, Enterococcus species, Bifidobacterium species, and yeast species.

[0167] In some specific embodiments, the probiotic is a probiotic strain. In some specific embodiments, it is specifically Bifidobacterium and / or Lactobacillus.

[0168] Suitable probiotic strains include: *Lactobacillus rhamnosus* ATCC 53103 (trademarked LGG from Valio Oy, Finland); *Lactobacillus rhamnosus* CGMCC 1.3724 (trademarked KI2 from BLIS Technologies Limited, New Zealand); *Lactobacillus paracasei* CNCM I-2116; *Lactobacillus johnsonii* CNCM I-1225; *Streptococcus salivarius* DSM 13084; *Bifidobacterium lactis* CNCM 1-3446 (trademarked Bb 12 from Christian Hansen company, Denmark); and *Bifidobacterium lactis* CNCM 1-3446 (trademarked Bb 12 from Morinaga Milk Industry Co., Ltd., Japan). Bifidobacterium longum ATCC BAA-999 sold by Japan under the trademark BB536; Bifidobacterium breve sold by Danisco under the trademark Bb-03; Bifidobacterium breve sold by Morinaga under the trademark M-16V; Bifidobacterium infantis sold by Procter & Gamble under the trademark Bifantis; and Bifidobacterium breve sold by the Rosell Institute of Biology, Canada under the trademark R0070.

[0169] On a dry weight basis, each g of the nutritional composition according to the invention may contain 10e3 cfu to 10e12 cfu of probiotic strains, more preferably between 10e7 cfu and 10e12 cfu, such as between 10e8 cfu and 10e10 cfu of probiotic strains.

[0170] In one embodiment, the probiotics are live. In another embodiment, the probiotics are non-replicating or inactivated. In some other embodiments, both live and inactivated probiotics may be present simultaneously.

[0171] The nutritional compositions of the present invention may also contain at least one bacteriophage (bacterial bacteriophage) or a mixture of bacteriophages, which are preferably targeted at pathogenic streptococci, Haemophilus, Moraxella and Staphylococci.

[0172] The nutritional compositions according to the present invention may be, for example, infant formula, stage 1 infant formula, stage 2 or follow-up infant formula, baby food, infant cereal compositions, fortifiers (such as human milk fortifiers), or supplements. In some specific embodiments, the compositions of the present invention are infant formula, fortifiers, or supplements intended for use in infants aged 4 months or 6 months. In a preferred embodiment, the nutritional compositions of the present invention are infant formula.

[0173] In some other embodiments, the nutritional composition of the present invention is a fortifier. The fortifier may be a breast milk fortifier (e.g., human milk fortifier) ​​or a formula food fortifier such as an infant formula fortifier or a stage 2 / follow-up formula fortifier.

[0174] When a nutritional composition is a supplement, it can be provided in unit dose form.

[0175] The nutritional compositions of the present invention may be in the form of solids (e.g., powder), liquids or gels.

[0176] The nutritional compositions according to the invention typically contain a protein source. The amount of protein can be from 1.6 g / 100 kcal to 3 g / 100 kcal. In some embodiments, particularly when the composition is used in preterm infants, the amount of protein can be between 2.4 g / 100 kcal and 4 g / 100 kcal or higher than 3.6 g / 100 kcal. In some other embodiments, the amount of protein can be lower than 2.0 g / 100 kcal, for example, between 1.8 g / 100 kcal and 2 g / 100 kcal, or lower than 1.8 g / 100 kcal.

[0177] The type of protein is considered irrelevant to this 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 soybean-based protein sources, can be used. Regarding the whey protein of interest, the protein source may be based on acidic whey or sweet whey, or mixtures thereof, and may contain any desired proportions of α-lactalbumin and β-lactoglobulin.

[0178] In some advantageous implementations, the protein source is whey-based (i.e., more than 50% of the protein comes from whey protein, such as 60% or 70%).

[0179] The protein may be intact or hydrolyzed, or a mixture of intact and hydrolyzed proteins. The term "intact" means that the major components of the protein are intact, i.e., the molecular structure is unchanged, for example, at least 80% of the protein is unchanged, for example, at least 85% of the protein is unchanged, preferably at least 90% of the protein is unchanged, and even more preferably at least 95% of the protein is unchanged, for example, at least 98% of the protein is unchanged. In one specific embodiment, 100% of the protein is unchanged.

[0180] The term "hydrolyzed" refers, in the context of this invention, to the hydrolysis or breakdown of a protein into its constituent amino acids.

[0181] The protein can be completely or partially hydrolyzed. For example, for infants or young children considered at risk of developing milk allergies, providing partially hydrolyzed protein (with a degree of hydrolysis between 2% and 20%) may be preferable. If a hydrolyzed protein is required, the hydrolysis process can be carried out as needed and as is known in the art. For example, whey protein hydrolysates can be prepared by enzymatic hydrolysis of whey fractions in one or more steps. If the whey fraction used as a raw material is substantially lactose-free, it has been found that the protein undergoes much less lysine blocking during hydrolysis. This allows the degree of lysine blocking to be reduced from about 15% by weight of total lysine to less than about 10% by weight of lysine; for example, about 7% by weight of lysine, which greatly improves the nutritional quality of the protein source.

[0182] In one embodiment of the invention, at least 70% of the protein is hydrolyzed, preferably at least 80% of the protein is hydrolyzed, for example at least 85% of the protein is hydrolyzed, even more preferably at least 90% of the protein is hydrolyzed, for example at least 95% of the protein is hydrolyzed, and especially at least 98% of the protein is hydrolyzed. In one specific embodiment, 100% of the protein is hydrolyzed.

[0183] In one specific embodiment, the protein in the nutritional composition is hydrolyzed, fully hydrolyzed, or partially hydrolyzed. The degree of hydrolysis (DH) of the protein may be between 8 and 40, or between 20 and 60, or between 20 and 80, or greater than 10, 20, 40, 60, 80, or 90.

[0184] In one embodiment, the nutritional composition according to the invention is a hypoallergenic composition. In another embodiment, the composition according to the invention is a hypoallergenic nutritional composition.

[0185] The nutritional compositions according to the invention typically contain a carbohydrate source. This is particularly preferred when the nutritional compositions of the invention are for infant formula. In this case, any carbohydrate source commonly found in infant formula can be used, such as lactose, sucrose, cane sugar, maltodextrin, starch, and mixtures thereof, but one of the preferred carbohydrate sources is lactose.

[0186] The nutritional compositions according to the invention typically contain a lipid source. This is particularly relevant when the nutritional compositions of the invention are for infant formula. In this case, the lipid source can be any lipid or fat suitable for use in infant formula. Some suitable fat sources include palm oil, high-oleic sunflower oil, and high-oleic safflower oil. The essential fatty acids linoleic acid and α-linolenic acid may also be added, as well as small amounts of oils containing large amounts of pre-formed arachidonic acid and docosahexaenoic acid, such as fish oil or microbial oil. The ratio of n-6 fatty acids to n-3 fatty acids in the fat source can be from about 5:1 to about 15:1, for example from about 8:1 to about 10:1.

[0187] The nutritional compositions of the present invention may also contain all vitamins and minerals considered essential for a daily diet, present in significant amounts in the composition. Minimum requirements for certain vitamins and minerals have been determined. Examples of minerals, vitamins, and other nutrients optionally present in the compositions of the present invention include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorus, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum, taurine, and L-carnitine. Minerals are typically added in the form of salts. The presence and amounts of specific minerals and other vitamins will vary depending on the target population.

[0188] If necessary, the nutritional compositions of the present invention may contain emulsifiers and stabilizers, such as soybean, lecithin, monoglyceride citrate, and diglyceride citrate.

[0189] The nutritional compositions of the present invention may also contain other substances that may have beneficial effects, such as lactoferrin, nucleotides, nucleosides, etc.

[0190] The nutritional compositions of the present invention may also contain carotenoids. In some specific embodiments of the present invention, the nutritional compositions of the present invention do not contain any carotenoids.

[0191] The nutritional compositions according to the invention can be prepared by any suitable means. The compositions will now be described by way of example.

[0192] For example, formulated foods, such as infant formula, can be prepared by blending protein sources, carbohydrate sources, and fat sources together in appropriate proportions. If an emulsifier is used, it can be added at this stage. Vitamins and minerals can be added at this stage, but are usually added later to avoid thermal degradation. Any lipophilic vitamins, emulsifiers, etc., can be dissolved in the fat source first before blending. Water, preferably reverse osmosis water, can then be added to form a liquid mixture. A suitable water temperature is between about 50°C and about 80°C to aid in the dispersion of the components. Commercially available liquefying agents can be used to form the liquid mixture.

[0193] Especially if the final product is in liquid form, fucoidylated oligosaccharides and N-acetylated oligosaccharides can be added at this stage. If the final product is in powder form, these components can also be added at this stage as needed.

[0194] Then, for example, homogenize the liquid mixture in two stages.

[0195] The liquid mixture can then be heat-treated to reduce the bacterial load, for example by rapidly heating the liquid mixture to a temperature between about 80°C and about 150°C and holding it for a time between about 5 seconds and about 5 minutes. This can be done by steam injection, autoclaving, or a heat exchanger (e.g., a plate heat exchanger).

[0196] The liquid mixture is then cooled, for example, to a temperature between approximately 60°C and approximately 85°C by rapid cooling. The liquid mixture is then homogenized again, for example, in two stages, with the pressure in the first stage between approximately 10 MPa and approximately 30 MPa, and the pressure in the second stage between approximately 2 MPa and approximately 10 MPa. 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 adjusted incidentally at this time.

[0197] 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 freeze dryer, and then converted into a powder. The moisture content of the powder should be less than about 5% by weight. Fucosylated oligosaccharides can also be added at this stage, or optionally, by dry mixing them with probiotic strains (if used), or by mixing them with probiotic strains in the form of crystalline syrup, followed by spray drying or freeze drying of the mixture.

[0198] If a liquid composition is preferred, the homogenized mixture can be sterilized and then packaged into a suitable container under aseptic conditions, or it can be packaged into a container first and then sterilized.

[0199] In another embodiment, the composition of the present invention may be a supplement.

[0200] Supplements may be in the form of tablets, capsules, lozenges, or liquids. Supplements may also contain protective hydrocolloids (such as gums, proteins, modified starches), binders, film-forming agents, encapsulation agents / materials, wall / shell materials, matrix compounds, coatings, emulsifiers, surfactants, solubilizers (oils, fats, waxes, lecithin, etc.), adsorbents, carriers, fillers, co-compounds, dispersants, wetting agents, processing aids (solvents), flow agents, flavor masking agents, weighting agents, gelling agents, and gelling agents. Supplements may also contain conventional pharmaceutical additives and adjuvants, excipients, and diluents, including but not limited to: water, gelatin of any origin, plant gums, lignin sulfonates, talc, sugars, starches, gum arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifiers, buffers, lubricants, coloring agents, wetting agents, fillers, etc.

[0201] In addition, supplements may contain organic or inorganic carrier materials suitable for oral or parenteral administration, as well as vitamins, trace minerals, and other micronutrients recommended by government agencies such as the USRDA.

[0202] The nutritional composition according to the present invention is for use with infants or young children. The infants or young children may be full-term or premature. In one specific embodiment, the nutritional composition of the present invention is for premature infants or young children.

[0203] The nutritional composition of the present invention can also be used for infants or young children delivered by cesarean section or vaginal delivery.

[0204] In some embodiments, the compositions according to the invention can be used before and / or during the weaning period.

[0205] The age and duration of administration (providement or feeding) of the nutritional composition can be determined as needed. The nutritional compositions of this invention can be used for preventative or therapeutic purposes: for the prevention and / or treatment of gastrointestinal infections and / or gastrointestinal inflammation in infants or young children.

[0206] In some embodiments, the nutritional composition is used for preventative purposes. The nutritional composition may be provided, for example, immediately after birth. The compositions of the present invention may also be provided within one week, two weeks, three weeks, one month, two months, three months, four months, six months, eight months, ten months, one year, two years, or even longer after birth. In some particularly advantageous embodiments of the invention, the nutritional composition is provided (or administered) to the infant during the first four or six months after birth.

[0207] In some other embodiments, the nutritional composition of the present invention is provided a few days (e.g., 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 20 days...), a few weeks (e.g., 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks...), or a few months (e.g., 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months...) after birth. This may specifically refer to cases where the infant is premature, but it is not necessary.

[0208] In one embodiment, the composition of the present invention may be provided to an infant or young child as a supplemental composition to breast milk. In some embodiments, the infant or young child is breastfed for at least the first 2 weeks, the first 1 month, 2 months, 4 months, or 6 months. In one embodiment, the nutritional composition of the present invention is provided to the infant or young child after the period of nutrition provided by breast milk, or provided to the infant or young child together with breast milk during the period of nutrition provided by breast milk. In another embodiment, the composition is provided to the infant or young child as the sole or primary nutritional composition for at least a period of time (e.g., after at least 1 month, 2 months, 4 months, or 6 months), or for at least 1 month, 2 months, 4 months, or 6 months.

[0209] In one embodiment, the nutritional composition of the present invention is a complete nutritional composition (meeting all or most of an individual's nutritional needs). In another embodiment, the nutritional composition is a supplement or fortifier intended for use, for example, as a supplement to human milk, or to supplement infant formula or stage 2 infant formula.

[0210] In some other embodiments, the nutritional compositions of the present invention are provided for therapeutic purposes. In these cases, the nutritional compositions of the present invention may be provided as needed for several days (1 day, 2 days, 3 days, 4 days, 5 days, 6 days...), or for several weeks (1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks or even more weeks), or for several months (1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months or even more months). The composition may be provided once these symptoms appear or once these health conditions / symptoms are diagnosed. The composition may be discontinued after the symptoms of the treated disease / condition have disappeared, or several days / weeks / months after the disappearance process.

[0211] The nutritional compositions according to the invention can be used for the prevention and / or treatment of gastrointestinal infections and / or inflammation. Intestinal infections and / or inflammation may have bacterial, viral, fungal, parasitic, environmental, or any other source, as detailed above. In some embodiments, these intestinal infections and / or inflammations have a bacterial source. In some other embodiments, they have a viral source.

[0212] Gastrointestinal infections and / or inflammations can be located in the upper and / or lower gastrointestinal tract. In one specific implementation, the infection and / or inflammation is located in the lower gastrointestinal tract.

[0213] For example, gastrointestinal infection and / or gastrointestinal inflammation can be enteritis, gastroenteritis, infectious diarrhea, enterocolitis, NEC, esophagitis, or any combination thereof.

[0214] Other objectives :

[0215] Another objective of this invention is to prepare a nutritional composition for the prevention and / or treatment of gastrointestinal infections and / or inflammation in infants or young children using at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, wherein:

[0216] - The ratio of fucoidylated oligosaccharides to N-acetylated oligosaccharides is 1:2 to 6.7:1; and

[0217] - N-acetylated oligosaccharides are selected from the list of the following: lactose-N-tetrasaccharide (LNT), lactose-N-neotetrasaccharide (LNnT), para-lactose-N-neohexose (para-LNnH), lactose-N-hexose, lactose-N-neohexose, para-lactose-N-hexose, para-lactose-N-neohexose, lactose-N-octasaccharide, lactose-N-neooctasaccharide, isol-lactose-N-octasaccharide, para-lactose-N-octasaccharide, and lactose-N-decasaccharide or any combination thereof.

[0218] The aforementioned implementation schemes and examples (e.g., relating to the type and amount of oligosaccharides, nutritional compositions, application, target population, etc.) are also applicable to this objective (i.e., use).

[0219] Another object of the present invention is to use a pharmaceutical composition comprising at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide for the prevention and / or treatment of gastrointestinal infections and / or gastrointestinal inflammation, wherein:

[0220] - The ratio of fucoidylated oligosaccharides to N-acetylated oligosaccharides is 1:2 to 6.7:1; and

[0221] - N-acetylated oligosaccharides are selected from the list of the following: lactose-N-tetrasaccharide (LNT), lactose-N-neotetrasaccharide (LNnT), para-lactose-N-neohexose (para-LNnH), lactose-N-hexose, lactose-N-neohexose, para-lactose-N-hexose, para-lactose-N-neohexose, lactose-N-octasaccharide, lactose-N-neooctasaccharide, isol-lactose-N-octasaccharide, para-lactose-N-octasaccharide, and lactose-N-decasaccharide or any combination thereof.

[0222] The aforementioned implementation schemes and examples (e.g., involving the type and amount of oligosaccharides, administration, and target population) are also applicable to this objective (i.e., pharmaceutical compositions).

[0223] Another object of the present invention relates to a method for preventing and / or treating gastrointestinal infections and / or gastrointestinal inflammation in infants or young children, the method comprising administering to the infant or young child a nutritional composition comprising at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, wherein

[0224] - The ratio of fucoidylated oligosaccharides to N-acetylated oligosaccharides is 1:2 to 6.7:1; and

[0225] - N-acetylated oligosaccharides are selected from the list of the following: lactose-N-tetrasaccharide (LNT), lactose-N-neotetrasaccharide (LNnT), para-lactose-N-neohexose (para-LNnH), lactose-N-hexose, lactose-N-neohexose, para-lactose-N-hexose, para-lactose-N-neohexose, lactose-N-octasaccharide, lactose-N-neooctasaccharide, isol-lactose-N-octasaccharide, para-lactose-N-octasaccharide, and lactose-N-decasaccharide or any combination thereof.

[0226] The various embodiments, details and examples described above (e.g., relating to the type and amount of oligosaccharides, nutritional compositions, application, target populations, etc.) are also applicable to these objectives (i.e., methods).

[0227] Example

[0228] The following examples illustrate some specific embodiments of the compositions used according to the present invention. The examples are given for illustrative purposes only and should not be construed as limiting the invention.

[0229] Example 1

[0230] Table 1 below provides examples of the components of a nutritional composition (e.g., infant formula) according to the present invention. This composition is given by way of example only.

[0231]

[0232] Table 1: Examples of components of the nutritional composition (e.g., infant formula) according to the present invention

[0233] Example 2

[0234] Research Description

[0235] Two parallel, controlled, single-blind, randomized, multicenter, interventional clinical trials were conducted. Infants no more than 14 days old were recruited and randomly assigned to one of two study cohorts. The study cohort consisted of either a conventional Stage 1 infant formula without HMOs [controlled trial] or the conventional Stage 1 infant formula supplemented with two HMOs [HMO].

[0236] The components of the tested infant formulas with or without added HMOs were equivalent to those shown in Table 1, with the following differences:

[0237] - The control infant formula does not contain oligosaccharides / HMOs (i.e., it does not contain 2'-fucosylated lactose and lactose-N-neotetrasaccharide).

[0238] - The tested HMO-containing infant formula contained 2'-fucosylated lactose, but in an amount of 1.24 g / L (corresponding to 0.86 g / 100 g powder before reconstitution; reconstituted at 129.18 g powder / 900 mL) and lactose-N-neotetrasaccharide, but in an amount of 0.63 g / L (corresponding to 0.44 g / 100 g powder before reconstitution; reconstituted at 129.18 g powder / 900 mL).

[0239] Start introducing complementary foods after 4 months of age.

[0240] The study consisted of a treatment period of 6 months ± 7 days, employing one of two treatments, and a 6-month follow-up period without treatment.

[0241] Discover

[0242] The inventors were surprised to find that infants in the HMO group (i.e., those fed conventional infant formula supplemented with 1.24 g / L 2'-fucosylated lactose and 0.63 g / L lactate-N-neotetrasaccharide) had fewer gastrointestinal infections, especially enteritis, gastroenteritis, and infectious diarrhea, from 0 to 12 months. Figure 1 The same effect was observed from 0 to 6 months.

[0243] In addition, the time of first onset of enteritis (including gastroenteritis) was delayed in the group of infants fed HMO-supplemented infant formula. Figure 2 ).

[0244] These data indicate that infants fed infant formula supplemented with 2'FL and LNnT in a ratio of approximately 2:1 received better protection against gastrointestinal infections / inflammation compared to infants fed the same infant formula without supplementation with 2'FL and LNnT. Therefore, compositions containing at least one fucoidylated oligosaccharide and at least one specific N-acetylated oligosaccharide (such as LNnT) in the stated proportions are highly effective for the prevention and / or treatment of intestinal infections and / or inflammation in infants.

Claims

1. A nutritional composition comprising at least one fucoidylated oligosaccharide and at least one N-acetylated oligosaccharide, said nutritional composition being used for the prevention and / or treatment of gastrointestinal infections and / or gastrointestinal inflammation in infants or young children, wherein... - The ratio of fucoidylated oligosaccharide to N-acetylated oligosaccharide is from 1:2 to 6.7:1; - The total amount of the fucoidylated oligosaccharides is from 0.5 g / L to 2 g / L of the composition, and / or, on a dry weight basis, the total amount of the fucoidylated oligosaccharides is from 0.34 g / 100 g to 1.4 g / 100 g of the composition; and - The N-acetylated oligosaccharides are selected from the list of the following: lactose-N-tetrasaccharide (LNT), lactose-N-neotetrasaccharide (LNnT), para-lactose-N-neohexose (para-LNnH), lactose-N-hexose, lactose-N-neohexose, para-lactose-N-hexose, para-lactose-N-neohexose, lactose-N-octasaccharide, lactose-N-neooctasaccharide, isol-lactose-N-octasaccharide, para-lactose-N-octasaccharide, and lactose-N-decasaccharide or any combination thereof.

2. The nutritional composition according to claim 1, wherein the fucosylated oligosaccharide is selected from the list of the following: 2'-fucosylvose, 3'-fucosylvose, difucosylvose, lactose-N-fucopentose I, lactose-N-fucopentose II, lactose-N-fucopentose III, lactose-N-fucopentose V, lactose-N-fucohexose, lactose-N-difucohexose I, fucosylvose-N-hexose, fucosylvose-N-neohexose I, fucosylvose-N-neohexose II, difucosylvose-N-hexose I, difucosylvose-N-neohexose I, difucosylvose-N-neohexose II, fucosylvose-P-lactose-N-hexose, and any combination thereof.

3. The nutritional composition according to any one of the preceding claims, wherein the fucoidylated oligosaccharide comprises a 2'-fucosylation epitope.

4. The nutritional composition according to any one of the preceding claims, wherein the fucoidylated oligosaccharide is 2'-fucosylated lactose (2'FL).

5. The nutritional composition according to any one of the preceding claims, wherein the N-acetylated oligosaccharide is selected from the list of the following: lactose-N-tetrasaccharide (LNT), lactose-N-neotetrasaccharide (LNnT), p-lactose-N-neohexose (p-LNnH), or any combination thereof, and preferably wherein the N-acetylated oligosaccharide is lactose-N-neotetrasaccharide (LNnT).

6. The nutritional composition according to any one of the preceding claims, wherein the nutritional composition comprises 2'-fucosyllactose (2'FL) and lactose-N-neotetrasaccharide (LNnT), or comprises a mixture of oligosaccharides consisting of 2'-fucosyllactose (2'FL) and lactose-N-neotetrasaccharide (LNnT).

7. The nutritional composition according to any one of the preceding claims, wherein the ratio of fucoidylated oligosaccharide to N-acetylated oligosaccharide is 1:1.5 to 4:1, such as 1:1 to 3:1, preferably 1.5:1 to 2.5:

1.

8. The nutritional composition according to any one of the preceding claims, wherein - The total amount of the fucoidylated oligosaccharides is from 0.75 g / L to 1.65 g / L of the composition, and / or, on a dry weight basis, the total amount of the fucoidylated oligosaccharides is from 0.52 g / 100 g to 1.15 g / 100 g of the composition; and / or - The total amount of the fucoidylated oligosaccharides is from 0.8 g / L to 1.5 g / L of the composition, and / or, on a dry weight basis, the total amount of the fucoidylated oligosaccharides is from 0.55 g / 100 g to 1.05 g / 100 g of the composition; and / or - The total amount of the fucoidylated oligosaccharides is from 0.85 g / L to 1.3 g / L of the composition, and / or, on a dry weight basis, the total amount of the fucoidylated oligosaccharides is from 0.59 g / 100 g to 0.9 g / 100 g of the composition; and / or - The total amount of the fucoidylated oligosaccharides is from 1 g / L to 1.25 g / L of the composition, and / or the total amount of the fucoidylated oligosaccharides is from 0.69 g / 100 g to 0.87 g / 100 g of the composition on a dry weight basis.

9. The nutritional composition according to any one of the preceding claims, wherein - The total amount of the N-acetylated oligosaccharides is from 0.3 g / L to 1 g / L of the composition, and / or, on a dry weight basis, the total amount of the N-acetylated oligosaccharides is from 0.2 g / 100 g to 0.7 g / 100 g of the composition; and / or - The total amount of the N-acetylated oligosaccharides is from 0.45 g / L to 0.85 g / L of the composition, and / or, on a dry weight basis, the total amount of the N-acetylated oligosaccharides is from 0.31 g / 100 g to 0.59 g / 100 g of the composition; and / or - The total amount of the N-acetylated oligosaccharides is 0.5 g / L to 0.8 g / L of the composition, and / or, on a dry weight basis, the total amount of the N-acetylated oligosaccharides is 0.35 g / 100 g to 0.56 g / 100 g of the composition; and / or - The total amount of the N-acetylated oligosaccharides is from 0.5 g / L to 0.75 g / L of the composition, and / or, on a dry weight basis, the total amount of the N-acetylated oligosaccharides is from 0.35 g / 100 g to 0.52 g / 100 g of the composition; and / or - The total amount of the N-acetylated oligosaccharides is from 0.5 g / L to 0.7 g / L of the composition, and / or, on a dry weight basis, the total amount of the N-acetylated oligosaccharides is from 0.35 g / 100 g to 0.49 g / 100 g of the composition.

10. The nutritional composition according to any one of the preceding claims, wherein The total amount of the fucoidylated oligosaccharides is from 1 g / L to 1.25 g / L of the composition, and / or, on a dry weight basis, the total amount of the fucoidylated oligosaccharides is from 0.69 g / 100 g to 0.87 g / 100 g of the composition; and The total amount of the N-acetylated oligosaccharides is from 0.5 g / L to 0.7 g / L of the composition, and / or, on a dry weight basis, the total amount of the N-acetylated oligosaccharides is from 0.35 g / 100 g to 0.49 g / 100 g of the composition.

11. The nutritional composition according to any one of the preceding claims, wherein the nutritional composition comprises at least one additional oligosaccharide and / or fiber and / or precursor thereof, said oligosaccharide and / or fiber and / or precursor thereof selected from the list comprising: galactooligosaccharide (GOS), fructooligosaccharide (FOS), xylooligosaccharide (XOS), inulin, polydextrose, sialylated oligosaccharide, sialic acid, fucose, and any combination thereof.

12. Nutritional composition according to any one of the preceding claims, said composition further comprising at least one probiotic bacteria in an amount of 10 3 to 10 12 cfu / g of the composition (dry weight).

13. The nutritional composition according to any one of the preceding claims, wherein the nutritional composition is an infant formula, stage 1 infant formula, stage 2 or follow-up infant formula, baby food, infant cereal composition, fortifier or supplement.

14. The nutritional composition according to any one of the preceding claims, wherein the gastrointestinal infection and / or the gastrointestinal inflammation is an infection and / or inflammation of the lower gastrointestinal tract.

15. The nutritional composition according to any one of the preceding claims, wherein the gastrointestinal infection and / or gastrointestinal inflammation has a bacterial, viral, fungal, parasitic, or environmental origin.

16. The nutritional composition according to any one of the preceding claims, wherein the gastrointestinal infection and / or the gastrointestinal inflammation is selected from the list of: enteritis, gastroenteritis, infectious diarrhea, enterocolitis, NEC, esophagitis, or any combination thereof.

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