Dietary butyrate

Abstract

To provide a composition for use in improving or maintaining gastrointestinal health.SOLUTION: Provided is a composition comprising a compound having formula (1), (2), (3), or (4), or a combination thereof, wherein R1, R2, R3, R4, R5, and R6 are independently a long chain fatty acid having 16 to 20 carbons.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to butyrate food ingredients having improved organoleptic properties. [Background technology]

[0002] The salts and esters of butyric acid are called butyrate or butanoate.Ester form of butyric acid is found in many foods, for example, milk, especially goat, sheep, cow, camel and buffalo milk, and milk-derived products, for example, butter, and cheese, for example, Parmesan cheese.Butyric acid is also the product of anaerobic fermentation, for example, the fermentation product produced by intestinal flora.

[0003] The numerous beneficial effects of butyrate are well documented in mammals and livestock: at intestinal concentrations, butyrate acts to modulate transepithelial fluid transport, mucosal inflammatory and oxidative status, enhances intestinal barrier function, and influences visceral sensitivity and intestinal motility.

[0004] Butyrate has been shown to improve intestinal structure in piglets with short bowel syndrome (Bartholome et al., J of Parenter Enteral Nutr. 2004;28(4):210-222) and reduce colon cancer cell growth in human cell lines (Lupton, J Nutr., 2004;134(2):479-482). The production of volatile fatty acids such as butyrate from fermentable fiber may contribute to the role of dietary fiber in colon cancer (Lupton, The Journal of Nutrition. 134(2):479-82). Bacteria in the large intestine that feed on or ferment non-digestible fiber and / or prebiotics produce short-chain fatty acids (SCFAs). Examples of SCFAs include, but are not limited to, acetate, propionate, and butyrate. SCFAs, most notably butyrate, inhibit histone deacetylase at the Foxp3 locus and promote the generation of regulatory T cells in the colon (Furusawa Y, et al., Nature 2013;504(7480):446-450). Oral supplementation with butyrate enhances the antibacterial activity of intestinal macrophages and limits the spread of bacteria across the intestinal barrier. Butyrate also benefits colonocytes by increasing energy production. Additionally, butyrate has been shown to reduce the incidence of diarrhea (Berni Canani et al., Gastroenterol., 2004;127(2):630-634), improve gastrointestinal symptoms in individuals with diarrhea-predominant irritable bowel syndrome (Scarpellini et al., Dig Liver Dis., 2007;1(1):19-22), and enhance small intestinal growth in neonatal pigs (Kotunia et al., J Physiol Pharmacol. 2004;55(2):59-68).

[0005] Tributyrin is a triglyceride consisting of three ester functional groups with three butyrate moieties and a glycerol backbone. Under hydrolysis conditions, such as those encountered during digestion, tributyrin can provide a source of three moles of butyric acid per mole of tributyrin. However, the effectiveness of tributyrin can be limited by rapid lipolysis in the stomach.

[0006] Both butyric acid and tributyrin are food additives generally regarded as safe (GRAS) (21 CFR 582.60 and 21 CFR 184.1903, respectively) and are natural components of many dairy products. However, butyric acid is associated with negative organoleptic qualities, such as vomit-, fecal-, and cheese-like odor characteristics. Tributyrin also has negative organoleptic qualities, particularly a highly bitter taste. These unpleasant taste and odor characteristics can make oral administration of compositions containing these compounds particularly difficult, especially in pediatric populations.

[0007] Therefore, it would be beneficial to provide a food-grade butyrate source with improved organoleptic properties compared to available solutions. A liquid format would offer additional advantages due to ease of formulation and reduced dissolution and homogenization issues. Summary of the Invention

[0008] The present invention provides compounds that are sources of butyric acid and have improved organoleptic properties. In particular, the compounds have improved odor and / or taste compared to butyric acid, butyrate salts, and tributyrin. The compounds can be used as a food source of butyric acid. The compounds can be used, for example, in nutritional compositions, dietary supplements, infant formula (infant milk), and follow-on milk.

[0009] Advantageously, the compounds of the present invention have been found to exhibit low rates of lipolysis in the stomach, and may result in effective delivery of butyric acid to the intestinal region.

[0010] According to a first aspect of the present invention, there is provided a method for producing a butyric acid or butyrate source having improved organoleptic properties, comprising the steps of: [ka] [In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently a long-chain fatty acid having 16 to 20 carbons, or a combination thereof.

[0011] The compounds of Formula (1), Formula (2), Formula (3), and / or Formula (4) may be present in compositions such as, for example, nutritional formulas, dietary supplements, infant formulas, or follow-on milks.

[0012] In one embodiment, the improved organoleptic property is improved odor. In one embodiment, the improved organoleptic property is improved taste. In one embodiment, the improved organoleptic property is improved odor and improved taste. In one embodiment, the improved taste is reduced bitterness.

[0013] According to another aspect of the present invention, to provide a source of butyrate or butyric acid, [ka] [In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently long-chain fatty acids having 16 to 20 carbons], or a combination thereof.

[0014] Dietary supplements may be in the form of, for example, capsules, tablets, sachets, liquids / oils, or powders.

[0015] According to another aspect of the present invention, [ka] [In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently a long-chain fatty acid having 16 to 20 carbons], or a combination thereof.

[0016] According to another aspect of the present invention there is provided the use of an infant formula or follow-on milk of the present invention to provide a source of butyrate or butyric acid having improved organoleptic properties.

[0017] According to another aspect of the present invention, there is provided a method for improving or maintaining gastrointestinal (GI) health comprising administering to a subject a compound of formula [ka] [In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently a long-chain fatty acid having 16 to 20 carbons, or a combination thereof.

[0018] According to another aspect of the present invention, there is provided a method of improving or maintaining GI health in a patient, comprising administering to a subject an amount of an active ingredient of formula [ka] [In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6are independently a long-chain fatty acid having 16 to 20 carbons], or a combination thereof.

[0019] In one embodiment, a combination of a compound having formula (1) and a compound having formula (2) is used as defined herein or present in a composition as defined herein (e.g., a nutritional composition, a dietary supplement, an infant formula, or a follow-on milk). Preferably, the compound having formula (1) is present in an amount of at least 10% by weight of the total triglycerides in the composition, and the compound having formula (2) is present in an amount of at least 10% by weight of the total triglycerides in the composition.

[0020] In one embodiment, a combination of a compound having formula (1) and a compound having formula (2) is used as defined herein or present in a composition as defined herein (e.g., a nutritional composition, a dietary supplement, an infant formula, or a follow-on milk), wherein the compound having formula (1) is present in an amount of at least 10% by weight of the total amount of butyric acid-containing triglycerides in the composition, and the compound having formula (2) is present in an amount of at least 10% by weight of the total amount of butyric acid-containing triglycerides in the composition.

[0021] In another embodiment, a combination of a compound having formula (1) and a compound having formula (2) is used as defined herein or present in a composition as defined herein (e.g., a nutritional composition, a dietary supplement, an infant formula, or a follow-on milk), wherein the compound having formula (1) is present in an amount of at least 15% by weight of the total amount of butyric acid-containing triglycerides in the composition, and the compound having formula (2) is present in an amount of at least 15% by weight of the total amount of butyric acid-containing triglycerides in the composition.

[0022] In one embodiment, a combination of a compound having formula (1), a compound having formula (2), a compound having formula (3), and a compound having formula (4) is used as defined herein or is present in a composition as defined herein, i.e., a nutritional composition, a dietary supplement, an infant formula, or a follow-on milk.

[0023] In one embodiment, R as defined herein 1 , R 2 , R 3 , R 4 , R 5 , and / or R 6 is an unsaturated fatty acid, preferably a monounsaturated one.

[0024] In one embodiment, R as defined herein 1 , R 2 , R 3 , R 4 , R 5 , and / or R 6 is selected from the group consisting of oleic acid, palmitic acid, stearic acid, or linoleic acid.

[0025] In one embodiment, R as defined herein 1 , R 2 , R 3 , R 4 , R 5 , and / or R 6 is oleic acid.

[0026] In one embodiment, R as defined herein 1 , R 2 , R 3 , R 4 , R 5 , and / or R 6 is palmitic acid.

[0027] In one embodiment, compound (1) is 1,3-dibutyryl-2-palmitoylglycerol.

[0028] In one embodiment, R 1, R 2 , R 3 , R 4 , R 5 , and / or R 6 Each of these is oleic acid.

[0029] In one embodiment, the compound having formula (1) is:

[0030] [ka] In one embodiment, the compound having formula (2) is:

[0031] [ka] In one embodiment, the compound having formula (3) is:

[0032] [ka] In one embodiment, the compound having formula (4) is:

[0033] [ka] According to another aspect of the present invention, [ka] wherein the compound having formula (5) comprises at least 10% by weight of the total triglycerides in the composition, and the compound having formula (6) comprises at least 10% by weight of the total triglycerides in the composition.

[0034] In one embodiment, the compounds having formula (5) comprise at least 15% by weight of the total triglycerides in the composition, and the compounds having formula (6) comprise at least 15% by weight of the total triglycerides in the composition.

[0035] In one embodiment, the compounds having formula (5) comprise at least 15% by weight of the total triglycerides in the composition, and the compounds having formula (6) comprise at least 20% by weight of the total triglycerides in the composition.

[0036] In one embodiment, the compounds having formula (5) comprise at least 20% by weight of the total triglycerides in the composition, and the compounds having formula (6) comprise at least 20% by weight of the total triglycerides in the composition.

[0037] In one embodiment, the compound having formula (5) comprises about 15% to about 30% by weight of the total triglycerides in the composition, and the compound having formula (6) comprises about 20% to about 30% by weight of the total triglycerides in the composition.

[0038] In one embodiment, the composition has the formula [ka] and preferably the compound having formula (7) constitutes at least 2% or 3% by weight of the total triglycerides in the composition, and / or a compound having formula: [ka] Preferably, the compound having formula (8) comprises at least 2% or 3% by weight of the total triglycerides in the composition.

[0039] According to another embodiment of the present invention, the compound of formula [ka] wherein the compounds having formula (5) constitute at least 10% by weight of the total amount of butyrate-containing triglycerides in the composition, and the compounds having formula (6) constitute at least 10% by weight of the total amount of butyrate-containing triglycerides in the composition.

[0040] In one embodiment, the compounds having formula (5) comprise at least 15% by weight of the total butyrate-containing triglycerides in the composition, and the compounds having formula (6) comprise at least 15% by weight of the total butyrate-containing triglycerides in the composition.

[0041] In one embodiment, the compounds having formula (5) comprise at least 15% by weight, preferably at least 20% by weight, of the total butyrate-containing triglycerides in the composition, and the compounds having formula (6) comprise at least 20% by weight, preferably at least 25% by weight, of the total butyrate-containing triglycerides in the composition.

[0042] In one embodiment, the composition further comprises a compound having formula (7), preferably comprising at least 2% or 3% by weight of the total amount of butyrate-containing triglycerides in the composition, and / or the composition further comprises a compound having formula (8), preferably comprising at least 2% or 3% by weight of the total amount of butyrate-containing triglycerides in the composition.

[0043] The composition of the present invention includes 1,3-dibutyryl-2-linoleoylglycerol, 1,3-dibutyryl-2-stearoylglycerol, 1-butyryl-2-oleoyl-3-palmitoylglycerol, 1-palmitoyl-2-oleoyl-3-butyrylglycerol, 1-butyryl-2-oleoyl-3-linoleoylglycerol, 1-linoleoyl-2-oleoyl-3-butyrylglycerol, 1-oleoyl-2-butyryl-3-linoleoylglycerol, 1-linoleoyl-2-butyryl-3-oleoylglycerol, 1-butyryl-2-linoleoyl-3-oleoylglycerol , 1-oleoyl-2-linoleoyl-3-butyrylglycerol, 1-butyryl-2-stearoyl-3-oleoylglycerol, 1-oleoyl-2-stearoyl-3-butyrylglycerol, 1-butyryl-2-oleoyl-3-stearoylglycerol, 1-stearoyl-2-oleoyl-3-butyrylglycerol, 1,2-dioleoyl-3-palmitoylglycerol, 1-palmitoyl-2,3-dioleoylglycerol, 1,2-dioleoyl-3-linoleoylglycerol, and / or 1-linoleoyl-2,3-dioleoylglycerol.

[0044] The compositions of the present invention may be in the form of a nutritional composition.

[0045] The compositions of the present invention may be in the form of an infant formula or a follow-on milk.

[0046] The compositions of the present invention may be in the form of a dietary supplement.

[0047] According to another aspect of the present invention there is provided the use of a composition as defined herein to provide a source of butyrate or butyric acid having improved organoleptic properties.

[0048] According to another aspect of the present invention, there is provided a method of providing a source of butyric acid having improved organoleptic properties to a subject, the method comprising administering to said subject an effective amount of a composition as defined herein.

[0049] According to another aspect of the present invention there is provided a composition as defined herein for improving or maintaining gastrointestinal health.

[0050] According to another aspect of the present invention, there is provided a method of improving or maintaining gastrointestinal health in a subject, the method comprising administering to the subject an effective amount of a composition as defined herein. [Brief explanation of the drawings]

[0051] [Figure 1] Figure 1 shows the release of fatty acids from emulsions containing 200 mg of (A) tributyrin, (B) high oleic sunflower oil, and (C) a mixture of butyrate moieties-containing triacylglycerols (TAGs) according to the present invention, digested either i) in simulated intestinal fluid (SIF) or (ii) sequentially in gastric fluid (SGF) followed by simulated intestinal fluid (SIF). [Figure 2] 1 shows the overall extent of lipid digestion for a mixture of tributyrin, high oleic sunflower oil, and TAG containing butyrate moieties according to the present invention after both SIF and SGF-SIF. DETAILED DESCRIPTION OF THE INVENTION

[0052] triglycerides Triglycerides (also called triacylglycerols) are triesters derived from glycerol and three fatty acids.

[0053] Fatty acids are carboxylic acids with long tails (chains). Fatty acids can be either unsaturated or saturated. Fatty acids that are not bound to other molecules are called free fatty acids (FFA).

[0054] The term "fatty acid moiety" refers to the portion of a triglyceride derived from a fatty acid in an esterification reaction with glycerol. The triglycerides used in the present invention contain at least one butyric acid moiety and at least one long chain fatty acid moiety.

[0055] Preferred long chain fatty acids for use in the present invention are those having 16 to 20 carbon atoms.

[0056] Examples of long chain fatty acids include oleic acid, palmitic acid, stearic acid, and linoleic acid.

[0057] The triglycerides of the present invention can be synthesized, for example, by esterification of long chain fatty acids and butyric acid with glycerol.

[0058] The triglycerides of the present invention can be synthesized, for example, by transesterification between tributyrin and another triglyceride containing long-chain fatty acids. In one embodiment, high oleic sunflower oil is the source of the long-chain fatty acids. This produces a triglyceride containing primarily butyrate and oleate moieties. Oleic acid is the primary fatty acid present in breast milk. This compound is dairy-free, cholesterol-free, and animal-derived-free. The fatty acids are released from the triglyceride by naturally occurring lipases in the gastrointestinal tract. Compared to butyrate salts, this compound does not add additional mineral salts to the final formulation.

[0059] Alternative methods for triglyceride synthesis can be determined by those skilled in the art as part of routine procedures. As an example, a method for obtaining 1,3-dibutyryl-2-palmitoylglycerol (BPB) is shown below.

[0060] [ka] A single butyrate moiety-containing triglyceride can be used herein, or a mixture of different butyrate moiety-containing triglycerides can be used.

[0061] composition The present invention provides a composition comprising the butyrate-containing triglycerides referred to herein. The composition may be, for example, a nutritional composition, a dietary supplement, an infant formula, or a follow-on milk.

[0062] The expression "nutritional composition" refers to a composition that provides nutrition to a subject. This nutritional composition is preferably taken orally and may comprise a lipid or fat source and a protein source. Such a composition may also contain a carbohydrate source. In one embodiment, the nutritional composition contains only a lipid or fat source. In other specific embodiments, the nutritional composition contains a lipid (or fat) source together with a protein source, a carbohydrate source, or both.

[0063] In some particular embodiments, the nutritional compositions according to the present invention are "enteral nutritional compositions," i.e., foodstuffs in which administration of the composition involves the gastrointestinal tract. Introduction to the stomach may involve the use of a tube that is passed through the oral / nasal passages or through the abdomen and leads directly to the stomach. Such a tube may be used, particularly in a hospital or clinic setting.

[0064] The composition according to the invention may be an infant formula (e.g. an infant starter formula), a follow-up or follow-on milk, a growing-up milk, a baby food, an infant cereal composition, a fortifier such as a breast milk fortifier, or a dietary supplement.

[0065] As used herein, the expression "infant formula" refers to a food product intended for the specific nutritional supplementation of infants during the first month of life, where the milk itself meets the nutritional requirements of infants falling within this category (e.g., Article 2(c) of the European Commission Directive 91 / 321 / EEC 2006 / 141 / EC of 22 December 2006 on infant formulas and follow-on milks).

[0066] Starter formulas are generally breast milk substitutes for infants from birth onwards. Follow-up or follow-on milks are offered from the sixth month onwards. These milks constitute the main liquid component of the increasingly varied diet of infants in this category. "Growing-up milks" (or GUMs) are offered from the first year onwards. These milks are generally dairy-based drinks specifically tailored to the nutritional needs of children.

[0067] The term "fortifier" refers to a liquid or solid nutritional composition suitable for mixing with breast milk (human milk) or infant formula. The term "breast milk" is to be understood as mother's milk or mother's colostrum, or donor's milk or the colostrum of donor's milk.

[0068] The term "dietary supplement" can be used to supplement an individual's nutrition (typically for the purpose of supplementing nutrition, but can also be added to any type of composition intended for ingestion). It can be in the form of, for example, a tablet, capsule, lozenge, or liquid. Dietary supplements can also contain protective hydrocolloids (gums, proteins, modified starches, etc.), binders, film-forming agents, encapsulating 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, taste-masking agents, bulking agents, jellifying agents, and gel-forming agents. Dietary supplements may also contain conventional pharmaceutical additives and adjuvants, excipients, and diluents, including, but not limited to, water, gelatin of any origin, vegetable gums, lignin sulfonate, talc, sugar, starch, gum arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifiers, buffers, lubricants, coloring agents, wetting agents, fillers, and the like.

[0069] In another particular embodiment, the nutritional composition of the present invention is a fortifier. The fortifier may be a breast milk fortifier or a formula fortifier, such as an infant formula fortifier. Thus, a fortifier is a particularly advantageous embodiment when the infant or toddler is premature.

[0070] If the composition is a dietary supplement, it may be provided in unit dose form.

[0071] Nutritional compositions of the present invention, particularly infant formulas, generally contain a protein source, a carbohydrate source, and a lipid source, although in some embodiments, particularly when the nutritional composition of the present invention is a dietary supplement or fortifier, only lipid (or a lipid source) may be present.

[0072] The nutritional compositions according to the present invention may contain a protein source. The protein may be in an amount of 1.6-3 g / 100 kcal. In some embodiments, particularly when the composition is intended for premature infants / toddlers, the protein amount may be 2.4-4 g / 100 kcal, or greater than 3.6 g / 100 kcal. In some other embodiments, the protein amount may be less than 2.0 g / 100 kcal, for example, 1.8-2 g / 100 kcal, or less than 1.8 g / 100 kcal.

[0073] For example, protein sources based on whey, casein, and mixtures thereof can be used, as well as plant-based protein sources, such as soybeans. With regard to whey protein, the protein source can be based on acid whey or sweet whey, or a mixture thereof, and can contain α-lactalbumin and β-lactoglobulin in any desired proportion. In some embodiments, the primary protein source is whey (i.e., more than 50%, e.g., more than 60% or more than 70% of the protein is derived from whey protein). The protein can be an intact protein or a hydrolyzed protein, or a mixture of intact and hydrolyzed protein. The term "intact" means that the majority of the protein is intact, i.e., the molecular structure is unchanged, e.g., at least 80% of the protein is unchanged, e.g., 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, e.g., at least 98% of the protein is unchanged. In certain embodiments, the protein is completely unchanged.

[0074] The term "hydrolyzed" in the context of the present invention means that a protein has been hydrolyzed or broken down into its constituent amino acids.

[0075] Proteins can be either completely hydrolyzed or partially hydrolyzed. If hydrolyzed protein is required, the hydrolysis process can be carried out as desired as known in the art. For example, whey protein hydrolysates can be prepared by enzymatically hydrolyzing whey fractions in one or more steps. It has been found that if the whey fraction used as the starting material is substantially lactose-free, the protein is significantly less likely to suffer from lysine blackage during the hydrolysis process. This allows the degree of lysine blackage to be reduced from about 15% by weight of the total lysine to less than about 10% by weight of the total lysine, for example, about 7% by weight of lysine, which significantly improves the nutritional value of the protein source.

[0076] In a particular embodiment, the protein of the composition is hydrolyzed, fully hydrolyzed, or partially hydrolyzed. The degree of hydrolysis (DH) of the protein may be 2 to 20, or 8 to 40, or 20 to 60, or 20 to 80, or greater than 10, greater than 20, greater than 40, greater than 60, greater than 80, or greater than 90. For example, nutritional compositions containing hydrolysates having a degree of hydrolysis of less than about 15% are commercially available from the Nestle Company under the trade name Peptamen®.

[0077] At least 70%, 80%, 85%, 90%, 95%, or 97% of the protein may be hydrolyzed, hi certain embodiments, 100% of the protein is hydrolyzed.

[0078] In one particular embodiment, the protein of the composition is a plant-based protein.

[0079] The nutritional composition of the present invention may contain a carbohydrate source.This is particularly preferred when the nutritional composition of the present invention is an infant formula.In this case, any carbohydrate source commonly found in infant formula can be used, such as lactose, sucrose, maltodextrin, starch, and mixtures thereof, but one of the preferred carbohydrate sources for infant formula is lactose.The nutritional composition of the present invention may also contain all the vitamins and minerals that are considered to be essential in daily diets and in nutritionally significant amounts.Minimum requirements for certain vitamins and minerals have been established. Examples of minerals, vitamins, and other nutrients optionally present in the compositions of the present invention include vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorus, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum, taurine, and L-carnitine. Minerals are usually added in salt form. The presence and amount of specific minerals and other vitamins vary depending on the target population. If necessary, the nutritional compositions of the present invention may contain emulsifiers and stabilizers, such as soybeans, lecithin, and citric acid esters of mono- and diglycerides. The nutritional compositions of the present invention may also contain other substances that may have beneficial effects, such as lactoferrin, osteopontin, TGF-β, slgA, glutamine, nucleotides, and nucleosides.

[0080] The compositions of the present invention may further comprise at least one indigestible oligosaccharide (eg, a prebiotic), typically in an amount of 0.3 to 10% by weight of the composition.

[0081] Prebiotics are typically indigestible, meaning they are not broken down or absorbed in the stomach or small intestine. Thus, they remain intact upon entering the large intestine and are selectively fermented by beneficial bacteria there. Examples of prebiotics include certain oligosaccharides, such as fructooligosaccharides (FOS), inulin, xylooligosaccharides (XOS), polydextrose, or any mixture thereof. In certain embodiments, the prebiotic may be fructooligosaccharides and / or inulin. In certain embodiments, the prebiotic is a combination of FOS and inulin, such as in a product sold by BENEO-Orafti under the trade name Orafti® Oligofructose (formerly Raftilose®) or in a product sold by BENEO-Orafti under the trade name Orafti® Inulin (formerly Raftiline®). Another example is a combination of 70% short-chain fructooligosaccharides and 30% inulin, which is registered by Nestle under the trade name "Prebio1". The nutritional compositions of the present invention may also comprise at least one milk oligosaccharide, which may be a BMO (cow's milk oligosaccharide) and / or a HMO (human milk oligosaccharide). The compositions of the present invention may further comprise at least one probiotic (i.e., a probiotic strain), such as a probiotic strain.

[0082] The most commonly used probiotic microorganisms are bacteria and yeasts, mainly of the following genera: Lactobacillus spp., Streptococcus spp., Enterococcus spp., Bifidobacterium spp. and Saccharomyces spp.

[0083] In some particular embodiments, the probiotic is a probiotic strain, hi some particular embodiments, the probiotic strain is a Bifidobacterium and / or a Lactobacillus.

[0084] The nutritional composition according to the present invention may contain, on a dry weight basis, from 10e3 to 10e12 cfu of probiotic strain per gram of composition, more preferably from 10e7 to 10e12 cfu, for example from 10e8 to 10e10 cfu of probiotic strain per gram of composition.

[0085] In one embodiment, the probiotics are viable. In another embodiment, the probiotics are non-replicating or inactivated. The probiotics may also be parts of the probiotic, such as cell wall components or metabolic products of the probiotic. In some other embodiments, both viable and inactivated probiotics may be present. The nutritional compositions of the present invention may further comprise at least one phage (bacteriophage) or mixture of phages, preferably against pathogenic streptococci, Haemophilus, Moraxella, and Staphylococcus.

[0086] In one embodiment, the nutritional composition according to the present invention may be a dairy product. A dairy product is a product containing dairy products. Dairy products are generally made from a suitable mixture of concentrated milk protein and fat sources. Dairy products can be acidified. Dairy products include ready-to-drink dairy beverages, concentrated milk, evaporated milk, sweetened concentrated milk, milk powder, yogurt, fresh cheese, cheese, ice cream, and dairy spreads, such as spreadable fresh cheese, cottage cheese, quark, crème fraîche, clotted cream, and cream cheese. Milk powder can be produced, for example, by spray drying or freeze drying.

[0087] Depending on the fat content, dairy products can be prepared from full-fat or whole milk, semi-skimmed milk, skimmed milk, or low-fat milk. Skimmed milk is milk containing less than 0.1% milk fat. Semi-skimmed milk is milk containing 1.5% to 2.5% milk fat. Full-fat milk is typically milk containing 3% to 4% fat. The exact fat content of skimmed, semi-skimmed, and full-fat milk varies primarily depending on local food regulations.

[0088] Dairy products are generally made from cow's milk, but can also be made from buffalo milk, yak milk, goat milk, sheep milk, horse milk, donkey milk, camel milk, reindeer milk, moose milk, or combinations thereof.

[0089] Acidified dairy products can be obtained by fermentation with suitable microorganisms. Fermentation provides flavor and sourness to dairy products. Fermentation can also affect the texture of dairy products. In addition, the microorganisms used for fermentation are selected for their ability to ferment milk into edible fermented dairy products. Typically, the microorganisms are known for their beneficial properties. These microorganisms include lactic acid bacteria and yeasts. Some of these microorganisms can be considered probiotics. Examples of lactic acid bacteria include Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus, both of which are involved in the production of yogurt, or other lactic acid bacteria belonging to the genera Lactobacillus, Streptococcus, Lactococcus, Leuconostoc, Bifidobacterium, Pediococcus, or any mixture thereof.

[0090] Another example of a fermented dairy product, also called cultured dairy product or cultured dairy food, or cultured milk, is fermented buttermilk fermented with Lactococcus lactis (Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactisbiovare diacetylactis) and / or Leuconostoc mesenteroides subsp. cremoris.

[0091] The microorganisms may be live or inactivated.

[0092] Dairy analogs are products made in a similar manner to the dairy products described above, but using (all or part) a protein source other than dairy and / or using (all or part) an edible fat source other than dairy. Suitable protein sources include vegetable proteins, such as soy, potato, and pea. Suitable fat sources include oils and fats of plant or marine origin. Fats and oils are used interchangeably. Preparations similar to those described above are meant to include product processing in which the traditional whey separation step is omitted, since the dairy analog product's formulation allows for the elimination of the separation step.

[0093] The nutritional compositions according to the present invention may be prepared in any suitable manner.

[0094] For example, infant formula, or other formula, can be prepared by blending a protein source, a carbohydrate source, and a fat source together in appropriate proportions. If used, an emulsifier can be included at this point. Vitamins and minerals may be added at this point, but are typically added later to avoid thermal degradation. Any lipophilic vitamins, emulsifiers, etc., can be dissolved in the fat source before blending. Water, preferably treated with reverse osmosis, can then be mixed to form a liquid mixture. The temperature of the water is suitably in the range of about 50°C to about 80°C to aid in the dispersion of the ingredients. A commercially available liquefaction device can be used to form the liquid mixture.

[0095] Any oligosaccharides can be added at this stage, especially if the final product is to be in liquid form. If the final product is to be a powder, any oligosaccharides can likewise be added at this stage, if desired.

[0096] The liquid mixture is then homogenized, for example in two stages.

[0097] In one embodiment, the nutritional compositions of the present invention are given to infants or young children as a nutritional supplement to breast milk.

[0098] Compositions of the present invention may be, for example, in solid (eg, powder), liquid, or gelatinous form.

[0099] The compositions of the present invention may be, for example, tablets, dragees, capsules, gelcaps, powders, granules, solutions, emulsions, suspensions, coated particles, spray-dried particles, or pills.

[0100] The composition may be in the form of a pharmaceutical composition and may comprise one or more suitable pharmaceutically acceptable carriers, diluents and / or excipients.

[0101] Examples of such excipients suitable for the compositions described herein can be found in the "Handbook of Pharmaceutical Excipients", 2nd Edition, (1994), (A Wade and PJ Weller, eds.).

[0102] Acceptable carriers or diluents for therapeutic use are known in the pharmaceutical art and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (AR Gennaro edit. 1985).

[0103] The pharmaceutical compositions may comprise as, or in addition to, the carrier, excipient, or diluent any suitable binder, lubricant, suspending agent, coating agent, and / or solubilizing agent. Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, fluid lactose, β-lactose, and the like, corn sweeteners, natural and synthetic gums such as acacia, tragacanth, or sodium alginate, carboxymethylcellulose, and polyethylene glycol.

[0104] Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like.

[0105] Preservatives, stabilizers, dyes, and even flavoring agents may be included in the composition. Examples of preservatives include sodium benzoate, sorbic acid, and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents can also be used.

[0106] Gastrointestinal health The compounds defined herein are sources of butyrate / butyric acid and therefore can be used to improve or maintain gastrointestinal (GI) health.

[0107] In one embodiment, the compounds and compositions defined herein can be used for the treatment of inflammatory bowel disease, for example, Crohn's disease or ulcerative colitis.

[0108] It is well documented that butyrate has numerous beneficial effects on GI health: at intestinal concentrations, butyrate acts to modulate transepithelial fluid transport, mucosal inflammatory and oxidative status, strengthens the epithelial barrier, and modulates visceral sensitivity and intestinal motility.

[0109] Fatty acids, including butyrate, are the primary source of energy for cells in the colonic mucosa (Roedriger, Gut. 1980;21:793-798), most importantly for colonocytes in the distal region of the colon. The potent trophic effect of butyrate on the small intestinal mucosa has been observed in experimental animals (Guilloteau et al., 2 J Anim Feed Sci. 2004;13, Suppl. 1:393-396). A decrease in intestinal butyrate concentration leads to atrophy of the colonic mucosa, which is usually explained by a decrease in substrate availability to colonocytes. On the other hand, administration of butyrate into the colonic lumen induces weight gain, increased DNA synthesis, and deeper intestinal crypts (Kripke et al., J Parenter Enter Nutr. 1989;13:109-116).

[0110] High concentrations of butyrate, obtained by fermentation of insoluble dietary fiber or after anal administration of butyrate, can inhibit early and advanced stages of colon carcinogenesis through modulation of the transcription, expression, and activation of key proteins in the apoptotic cascade (Avivi-Green et al., J Nutr. 2002;132(7):1812-18).

[0111] Chapman et al. (Gut 1994;35(1):73-76) have shown that inflamed colonic mucosa sequesters much more butyrate than glutamine or glucose.

[0112] Experiments have shown that infusion of butyrate results in a significant reduction in inflammation and a decrease in the extent of ulceration of the colon wall in rats (Andoh et al., J Parenter Enter Nutr. 1999;23(5):70-73).

[0113] The effectiveness of butyrate enemas has been demonstrated by clinical observations in patients with ulcerative colitis (Han et al., Gastroenterol Clin North Am. 1999;28:423-443; Scheppach et al., Gastroenterol Suppl. 1997;222:53-57).

[0114] The direct anti-inflammatory activity of butyrate can be associated with the inhibition of nuclear factor kappa B (NFKB) translocation and butyrate binding to DNA, as well as, by the same evidence, the inhibition of the transcription and production of inflammatory cytokines (Segain et al., Gut. 2000;47:397-403).

[0115] Therefore, the triglyceride compounds from which butyrate is derived and which are used in the present invention may play a major role in maintaining intestinal homeostasis and GI health.

[0116] Administration Preferably, the compounds and compositions described herein are administered enterally.

[0117] Enteral administration may be, for example, oral or gastric.

[0118] In general terms, administration of the combinations or compositions described herein may be, for example, by the oral route or by another route to the gastrointestinal tract, for example, administration may be by tube feeding.

[0119] The subject may be a mammal, such as a human, dog, cat, horse, goat, cow, sheep, pig, deer, and primate. Preferably, the subject is a human. [Example]

[0120] Example 1. Preparation of triglycerides containing butyrate moieties A composition comprising butyrate-containing triglycerides was prepared by chemical interesterification between tributyrin and high oleic sunflower oil in the presence of a catalyst such as sodium methanoate. A molar excess of tributyrin compared to high oleic sunflower oil was used.

[0121] The three reagents, i.e., tributyrin, high oleic sunflower oil, and catalyst, were mixed in a reactor under nitrogen atmosphere and then heated with stirring at 80°C for 3 hours. After the reaction was complete, the product was washed with water and dried under vacuum (25 mBar, 60°C for 2 hours). The resulting oil product was then subjected to a decolorization step with the action of bleaching earth and purified either by short-path distillation (130°C, 0.001-0.003 mBar) and / or deodorization by air-water injection (160°C, 2 mBar, 2 hours).

[0122] The components of the resulting oil composition (mostly triglycerides) are shown in Table 1 below. These triglycerides are represented by the three fatty acids they contain. These fatty acids are represented by their lipid numbers: 4:0 for butyrate, 16:0 for palmitate, 18:0 for stearate, 18:1 for oleate, and 18:2 for linoleate. The central fatty acid is located at the sn-2 position of the triglyceride. As an example, 16:0-4:0-18:1 represents two different triglycerides, including molecules with butyrate at the sn-2 position and either palmitate at the sn-1 position and oleate at the sn-3 position, or oleate at the sn-1 position and palmitate at the sn-3 position.

[0123] The triglyceride profile and positional isomers were analyzed by liquid chromatography coupled to a high-resolution mass spectrometer, and the proportion of each lipid was assessed by liquid chromatography coupled to an evaporative light scattering detector (ELSD).

[0124] [Table 1] In the composition sample, the two most abundant triglycerides were 4:0-18:1-4:0 and 18:1-18:1-4:0, which together accounted for approximately 40-50 g / 100 g.

[0125] Example 2. Odor characteristics of triglycerides containing butyrate moieties In an odor comparison, a solution containing butyrate moiety-containing triglycerides (composed primarily of oleic and butyric fatty acids) was compared to a solution containing sodium butyrate.

[0126] Sample preparation Solutions containing butyrate-containing triglycerides (see Example 1) or sodium butyrate were prepared and stored at 4° C. until delivered to the sensory panelists. Each 250 mL solution contained 600 mg of butyric acid (equivalent to one capsule of sodium butyrate commercially available as a dietary supplement, at a concentration of 2.4 mg / mL) and 1% w / v BEBA Optipro 1 infant formula in acidified deionized water.

[0127] Samples were prepared the day before testing by placing 4 mL of each solution (triglyceride butyrate solution, sodium butyrate solution) into Agilent vials.

[0128] method A "2 vs. 5 test" was conducted. In this test, panelists were presented with five samples. They were asked to identify two samples that differed from the other three. The order in which the samples were presented was randomized to avoid bias due to the presentation order.

[0129] In addition to the 2 vs. 5 point test, a comment box was presented to the panelists to allow them to comment on the nature of the perceived difference (eg, odor intensity, odor quality).

[0130] result The five samples were presented simultaneously to panelists who were asked to remove the caps, smell, and then cap each vial in a predetermined order. The results are shown in Table 2.

[0131] [Table 2] P values ​​were calculated using a binomial test performed with Fizz software (Biosystems, France).

[0132] Panelists who distinguished correctly (butyrate moiety-containing TAGs different from sodium butyrate) described the sodium butyrate as smelling "cheese," while for the butyrate moiety-containing TAG samples, this "cheese" smell was greatly reduced and the odor was almost neutral.

[0133] Example 3. Taste characteristics of triglycerides containing butyrate moieties Sensory benchmarking of a solution containing butyrate moiety-containing triglycerides (see Example 1), composed primarily of oleic and butyric fatty acids, was performed against a solution containing tributyrin.

[0134] Sample preparation One tablespoon (4.6 g) of BEBA Optipro1 infant formula was added to warm water (boiled water cooled as per instructions) to a final volume of 150 mL (approximately a 3% w / v solution). Each triglyceride form of butyrate was weighed separately to provide 600 mg of butyrate, and infant formula was added to a final volume of 50 mL for each solution.

[0135] Solution A contained a butyrate moiety-containing triglyceride (see Example 1). Solution B contained tributyrin.

[0136] method A group of panelists conducted repeated blind tastings.

[0137] The samples were prepared immediately prior to the preliminary bitterness evaluation, and each solution was vigorously shaken. A small amount of each solution was simultaneously filled into tasting cups labeled A and B.

[0138] The two samples were presented simultaneously to panelists who were asked to taste the solution by taking a sip and spitting it out, and to rate the perceived bitterness on a scale of 0 to 10 (0 representing no perceived bitterness and 10 representing the most bitterness imaginable).

[0139] result The panelists rated the bitterness of Solution A as 4.33±1.52, mean±SD.

[0140] The panelists rated the bitterness of Solution B as 8.33±1.52, mean±SD.

[0141] These data indicate that the butyrate moiety-containing TAG composition was significantly less bitter to taste compared to tributyrin in infant formula.

[0142] Example 4. Taste characteristics of 1,3-dibutyryl-2-palmitoylglycerol 1,3-Dibutyryl-2-palmitoylglycerol (BPB) was synthesized as a single compound using the following synthesis.

[0143] [ka] When BPB was evaluated by a sensory panel using descriptive evaluation, it was found to have no distinctive taste or odor.

[0144] Example 5. Digestion of butyrate-containing triglycerides 5.1.Materials Sodium taurocholate, sodium chloride, hydrochloric acid, sodium hydroxide, potassium hydroxide, maleic acid, tris(hydroxymethyl)aminomethane, pepsin (Porcine, 800-111, 2500 U / mg, P7000, actual activity used 674 U / mg and 561 U / mg), pancreatin (Porcine, USP x8, P7585), and porcine bile extract (total bile salt content = 49% by weight; containing 10-15% glycodeoxycholic acid, 3-9% taurodeoxycholic acid, and 0.5-7% deoxycholic acid; 5% phospholipids, B8631) were used as received and purchased from Sigma-Aldrich (St Louis, MO, USA). Rabbit stomach extract (RGE70 ≥ 70 U / mL RGL and ≥ 280 U / mL pepsin) was purchased from Lipolytech (Marseille, France). All water used in this study was of purified Milli-Q quality. Tributyrin was from Sigma (food grade) and high oleic sunflower oil from Florin. Interesterified triglycerides were obtained by chemical interesterification using sodium methanoate (from Evonik) as catalyst.

[0145] 5.2. Emulsion Preparation Polyoxyethylene sorbitan monooleate (Tween® 80) was mixed into the oil phase at 40° C. and then mixed with the aqueous phase using a magnetic stirrer to prepare a 10 wt % oil-in-water emulsion stabilized with 0.3 wt % Tween 80. The emulsion was then created using a Hielscher UP400S ultrasonic probe homogenizer equipped with a 5 mm diameter rod probe, applying 100% amplitude at 100% cycle for 2 minutes, during which the sample was cooled using ice water.

[0146] 5.3. Particle size measurement The droplet size of each lipid emulsion was measured by laser light scattering using a Mastersizer 3000 equipped with a Hydro SM from Malvern Instruments (Malvern, Worcestershire, United Kingdom). The laser specifications for the two lasers were 4 mW, 632.8 nm, and 10 mW, 470 nm. To avoid multiple scattering effects, the sample was diluted to approximately 0.002 wt%. Information on emulsion particle size was then obtained by best agreement between the theory of light scattering (Mie) and the measured particle size distribution. A refractive index of 1.456 and an absorbance of 0.01 were used for the oil phase. The particle size of the emulsion was estimated as two values: the volume-surface mean diameter D3,2 (D3,2 1 / 4 Pnidi3 / nidi2) or the volume-length mean diameter D4,3 (D4,3 1 / 4 Pnidi4 / nidi3). The average of three measurements of two freshly prepared emulsions is taken as the emulsion particle size result.

[0147] 5.4.Statistical analysis Statistical analysis was performed using two-tailed t-tests with unequal variances using the software Igor Pro.

[0148] 5.5. In vitro digestion Lipid emulsions (2 mL) containing 200 mg of fat were subjected to in vitro gastrointestinal lipolysis. Digestion was performed in a thermostated glass vessel (37 °C) in a pH-STAT assembly controlled by a TIM 856 bi-burette pH-STAT (Radiometer Analytical, France). For gastric digestion, samples were incubated with 8.5 mL of simulated gastric fluid (SGF) consisting of 150 mM NaCl, 450 U / mL pepsin, and 18 U / mL rabbit gastric lipase at 37 °C and pH 5.5 for 90 min. Digestion was initiated by adding 18 U / mL rabbit gastric lipase (TBU, activity against tributyrin assessed at pH 5.4).

[0149] The intestinal digestion step was performed in a pH-STAT, and the pH was kept constant at 6.8 by adding NaOH (0.05M). A bile salt mixture (bile salts prepared in Tris buffer, 5 mM Tris, 150 mM NaCl) and a calcium solution (20 mM Ca, 176 mM Tris, 150 mM NaCl) were added to the SGF sample mixture. The mixture was transferred to the pH-STAT, and the pH was adjusted to approximately 6.78. The intestinal digestion step began when the temperature reached 37 ± 0.5°C. The pH was adjusted to 6.8 and incubated at this pH and temperature for 2 minutes, after which a pancreatin solution (5 mM Tris, 150 mM NaCl, pH 6.8) was added. The final composition of the intestinal fluid was 10 mM CaCl, 12 mM mixed bile salts, 0.75 mM phospholipids, 150 mM NaCl, and 4 mM tris(hydroxymethyl)aminomethane buffer. The intestinal digestion step was carried out for 3 hours in a Radiometer titration manager. During the intestinal digestion step, the digestion rate was followed using pH-STAT (TIM856, Radiometer) technique and expressed as titratable acids (rather than fatty acids) calculated by the following formula:

[0150] TA=V NaOH × 0:05 × 1000 TA: total amount of titratable acid released, mmol, V NaOH : Volume of NaOH used to titrate the acid released in 3 hours, mL.

[0151] 5.6.Results Because dietary lipid digestion involves both gastric and intestinal lipases, lipid digestibility was assessed using two digestion models: i) porcine pancreatic lipase (PPL) in simulated intestinal fluid (SIF), and ii) sequential digestion in simulated gastric fluid (SGF) with rabbit gastric lipase (RGL) followed by porcine pancreatic lipase (PPL) in simulated intestinal fluid (SIF). All lipids were emulsified with polyoxyethylene sorbitan monooleate (Tween® 80) and had similar particle size distributions and specific surface areas (Figure 2). This suggests that the differences in digestion are primarily due to the molecular structure of triglycerides.

[0152] Figures 1A-C (i) show the digestion of tributyrin (C4), high oleic sunflower oil (HOSFO, mostly C18:1), and the butyrate-containing triglyceride "C4-C18:1" of the present invention, prepared by chemical interesterification between tributyrin and high oleic sunflower oil (see Example 1), with porcine pancreatic lipase (from the spleen) in the presence of mixed bile and calcium (SIF model). The lipids generally exhibited the same lipolytic behavior, with an initial rapid lipolysis period in the first 15 minutes, which gradually slowed over the last 2.5 hours of simulated intestinal digestion. C4 triglycerides exhibited an initial maximum rate of lipolysis of 223 ± 59 μmol / min. The initial degradation rate of high oleic sunflower oil, 34.5 ± 2.3 μmol / min, was significantly lower than that of short-chain triglycerides (p < 0.0001). C4-C18:1 showed an initial hydrolysis rate of 153±47 μmol / min between C4 and C18:1. Overall, it can be seen that all triglycerides are rapidly and fully digested in the presence of porcine pancreatic lipase.

[0153] These triglycerides were then digested in a sequential SGF(RGL)SIF(PPL) model. Digestion in the SIF section is shown in Figure 1A-C (ii). Measurements in the stomach section were not performed due to limited ionization of the target fatty acids. Compared to digestion with SIF alone, C4 and C18:1 triglycerides generally released smaller amounts of titratable acid during the 3-hour digestion. The effect was greatest with tributyrin, which had a significantly lower (p<0.0001) initial lipolysis rate of 44.1±8.8 μmol / min during SGF-SIF digestion compared with 223±59 μmol / min for SIF alone. The total amount of acid released after SGF-SIF digestion of tributyrin (381±20 μmol) was nearly one-third of the amount released after digestion with SIF alone (958±12.5 μmol). These results clearly demonstrate that the digestion of tributyrin in the model stomach is substantial.

[0154] Sequential exposure to SGF and SIF resulted in a slight, but non-significant, decrease in the rate of SIF lipolysis of the butyrate-containing triglyceride C4-C18:1, 124 ± 20 μmol / min, compared with SIF alone (124 ± 20 μmol / min). The most interesting observation was that the decrease in SIF lipolysis caused by pre-exposure to RGL was influenced by the secondary fatty acid chain length. Originally, tributyrin reduced total fatty acid release during SIF lipolysis by 60.2% (147 ± 7.6 μmol) after pre-exposure to RGL in SGF. In comparison, C4-C18:1 transesterified triglycerides showed a 6.1% (45 ± 7.6 μmol) decrease.

[0155] The overall extent of lipid digestion after both SIF and SGF-SIF is presented in Figure 2 using direct and back titration for three triglycerides. Because many fatty acids are only partially ionized at pH 6.8, direct titration provides only a partial picture of the extent of lipid digestion; rather, back titration to pH 11.5 or GC-FAME analysis is required to estimate the overall extent of digestion. Back titration results for the three triglycerides showed that tributyrin and butyrate moiety-containing triglycerides C4-C18:1 were 101.5 ± 0.9% and 101 ± 1.6%, respectively, indicating complete digestion with the release of three fatty acids per molecule. Meanwhile, high oleic sunflower oil was 72.3 ± 2% digested, indicating complete digestion with the release of two fatty acids per molecule.

[0156] In general, tributyrin was found to be fully hydrolyzed in the stomach, while high-oleic sunflower oil triglycerides were found to be very limitedly hydrolyzed in the stomach. Surprisingly, butyrate-containing triglycerides prepared by transesterification of C4 with long-chain fatty acids (C4-C18:1) were found to reduce the extent of gastric lipolysis of C4 fatty acids. Tributyrin was approximately 60% lipolyzed by gastric lipase, as indicated by a reduction in total fatty acid release during SIF lipolysis after pre-exposure to RGL in SGF. In comparison, C4-C18:1 butyrate-containing triglycerides showed only a 6.1% reduction in total fatty acid release in SGF-SIF. These results suggest that transesterification of C4 with long-chain fatty acids (C4-C18:1) modulates butyrate release by delaying its release in the intestine after digestion rather than in the stomach, and that lipid design with this structure alters the timing (but not the degree) of short-chain fatty acid delivery to the gastrointestinal tract.

Claims

1. To provide a source of butyrate with improved organoleptic properties, 【Chemistry 1】 [In the formula, R １ , R ２ , R ３ , R ４ , R ５ , and R ６ are independently a long chain fatty acid having 16 to 20 carbons, or a combination thereof.

2. 2. The use according to claim 1, wherein the compound or combination thereof is present in a nutritional composition, preferably a nutritional supplement, an infant formula, or a follow-on milk.

3. To provide a source of butyrate, 【Chemistry 2】 [In the formula, R １ , R ２ , R ３ , R ４ , R ５ , and R ６ are independently long chain fatty acids having 16 to 20 carbons, or combinations thereof.

4. 4. The dietary supplement of claim 3 in the form of a capsule, tablet, sachet, or powder.

5. formula 【Transformation 3】 [In the formula, R １ , R ２ , R ３ , R ４ , R ５ , and R ６ are independently a long chain fatty acid having 16 to 20 carbons, or a combination thereof.

6. 6. An infant formula or follow-on milk according to claim 5 for providing a source of butyrate.

7. For use in improving or maintaining gastrointestinal (GI) health, 【Chemistry 4】 [In the formula, R １ , R ２ , R ３ , R ４ , R ５ , and R ６ are independently a long chain fatty acid having 16 to 20 carbons, or a combination thereof.

8. 10. The use according to claim 1 or 2, the nutritional supplement according to claim 3 or 4, the infant formula or follow-on milk according to claim 5 or 6, or the compound for use according to claim 7, wherein a combination of a compound having formula (1) and a compound having formula (2) is used, preferably in a composition comprising a compound having formula (1) in an amount of at least 10% by weight of the total amount of triglycerides and a compound having formula (2) in an amount of at least 10% by weight of the total amount of triglycerides.

9. 8. The use of claim 1 or 2, the dietary supplement of claim 3 or 4, the infant formula or follow-on milk of claim 5 or 6, or the compound for use of claim 7, wherein a combination of a compound having formula (1) and a compound having formula (2) is used, said combination being present in a composition comprising a compound having formula (1) in an amount of at least 10% by weight of the total amount of butyrate-containing triglycerides and a compound having formula (2) in an amount of at least 10% by weight of the total amount of butyrate-containing triglycerides.

10. 10. The use according to claim 1, 2, 8 or 9, the dietary supplement according to claim 3, 4, 8 or 9, the infant formula or follow-on milk according to claim 5, 6, 8 or 9, or the compound for use according to claim 7, 8 or 9, wherein a combination of a compound having formula (1), a compound having formula (2), a compound having formula (3) and a compound having formula (4) is used.

11. R １ , R ２ , R ３ , R ４ , R ５ , and / or R ６ is an unsaturated fatty acid, preferably a monounsaturated fatty acid;

12. R １ , R ２ , R ３ , R ４ , R ５ , and / or R ６ is selected from the group consisting of oleic acid, palmitic acid, or linoleic acid,

13. R １ , R ２ , R ３ , R ４ , R ５ , and R ６ each of which is oleic acid;

14. formula 【Transformation 5】 wherein the compound having formula (5) constitutes at least 10% by weight of the total triglycerides in the composition, and the compound having formula (6) constitutes at least 10% by weight of the total triglycerides in the composition.

15. 15. The composition of claim 14, wherein the compound having formula (5) comprises at least 15% by weight of the total triglycerides in the composition, and the compound having formula (6) comprises at least 20% by weight of the total triglycerides in the composition.

16. formula 【Transformation 6】 and preferably, the compound having formula (7) constitutes at least 2% by weight of the total triglycerides in the composition, and / or 【Transformation 7】 16. The composition of claim 14 or 15, further comprising a compound having the formula (8), wherein the compound having the formula (8) comprises at least 2% by weight of the total triglycerides in the composition.

17. formula 【Transformation 8】 wherein the compounds having formula (5) constitute at least 10% by weight of the total amount of butyrate moiety-containing triglycerides in the composition, and the compounds having formula (6) constitute at least 10% by weight of the total amount of butyrate moiety-containing triglycerides in the composition.

18. 18. The composition of claim 17, wherein the compounds having formula (5) constitute at least 15%, preferably at least 20%, by weight of the total amount of butyrate-containing triglycerides in the composition, and the compounds having formula (6) constitute at least 20%, preferably at least 25%, by weight of the total amount of butyrate-containing triglycerides in the composition.

19. 19. The composition of claim 17 or 18, further comprising a compound having formula (7), preferably wherein said compound having formula (7) constitutes at least 2% by weight of the total amount of butyrate-containing triglycerides in said composition, and / or further comprising a compound having formula (8), preferably wherein said compound having formula (8) constitutes at least 2% by weight of the total amount of butyrate-containing triglycerides in said composition.

20. 1,3-Dibutyryl-2-linoleoylglycerol, 1,3-Dibutyryl-2-stearoylglycerol, 1-Butyryl-2-oleoyl-3-palmitoylglycerol, 1-Palmitoyl-2-oleoyl-3-butyrylglycerol, 1-Butyryl-2-oleoyl-3-linoleoylglycerol, 1-Linoleoyl-2-oleoyl-3-butyrylglycerol, 1-Oleoyl-2-butyryl-3-linoleoylglycerol, 1-Linoleoyl-2-butyryl-3-oleoylglycerol, 1-Butyryl-2-linoleoyl-3-oleoylglycerol, 1-Oleoyl-2-linoleoyl 20. The composition of any one of claims 14 to 19, further comprising 1,2-dioleoyl-3-palmitoylglycerol, 1-palmitoyl-2,3-dioleoylglycerol, 1,2-dioleoyl-3-linoleoylglycerol, and / or 1-linoleoyl-2,3-dioleoylglycerol.

21. The composition according to any one of claims 17 to 20, wherein the composition is a nutritional composition.

22. The composition of any one of claims 14 to 20, wherein the composition is an infant formula, a follow-on milk, or a nutritional supplement.

23. 23. Use of a composition according to any one of claims 14 to 22 to provide a source of butyrate with improved organoleptic properties.

24. A composition according to any one of claims 14 to 22 for improving or maintaining gastrointestinal health.

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