Dietary butyrate

Abstract

The present invention relates to dietary butyrates, in particular nutritional compositions for providing a butyrate or butyric acid source, comprising a compound of formula (1) wherein R6 is a long chain fatty acid having 16 to 20 carbons. # imgabs0 #

Description

[0001] This application is a divisional application of the international application with application number PCT / EP2020 / 084731 and invention name “Dietary Butyrate” filed on December 4, 2020. The international application entered the Chinese national phase on May 26, 2022 with application number 202080082527.7. Technical Field

[0002] The present invention relates to dietary sources of butyrate. Background Art

[0003] Salts and esters of butyric acid are called butyrates or butanoates. Butyric acid in ester form is present in many foods, such as milk, especially milk of goats, sheep, cattle, camels and buffaloes, and dairy products such as butter and cheeses such as Parmesan cheese. Butyric acid is also a product of anaerobic fermentation, for example, as a product of fermentation produced by intestinal microflora.

[0004] The multiple beneficial effects of butyrate are well documented in mammals and livestock. At the intestinal level, butyrate modulates transepithelial fluid transport, mucosal inflammation and oxidative status, enhances intestinal barrier function, and influences visceral sensitivity and intestinal motility.

[0005] 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 the proliferation of colon cancer cells 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). Short-chain fatty acids (SCFAs) including but not limited to acetate, propionate, and butyrate are produced by colonic bacteria that ingest or ferment non-digestible fiber and / or prebiotics. SCFAs, and most notably butyrate, promote regulatory T cells in the colon via histone deacetylase inhibition at the Foxp3 locus (Furusawa Y et al., Nature 2013; 504(7480): 446-450). Oral butyrate supplementation promotes the antibacterial activity of intestinal macrophages and limits the spread of bacteria beyond the intestinal barrier. Butyrate also benefits colonocytes by increasing energy production. In addition, 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-type irritable bowel syndrome (Scarpellini et al., Dig Liver Dis., 2007; 1 (1): 19-22) and promote the development of the small intestine in newborn piglets (Kotunia et al., J Physiol Pharmacol. 2004; 55 (2): 59-68).

[0006] Tributyrin is a triglyceride composed of three ester functional groups, with three butyrate moieties and a glycerol backbone. Under hydrolytic conditions, such as those occurring during digestion, tributyrin may be a source of three moles of butyric acid per mole of tributyrin. However, the efficacy of tributyrin may be limited by its rapid gastric lipolysis.

[0007] Butyric acid and tributyrin are generally regarded as safe (GRAS) (21 CFR582.60 and 21 CFR184.1903, respectively) food additives and are natural components of many dairy products. However, butyric acid is associated with negative organoleptic qualities, such as vomit-like, fecal-like, and cheese-like aroma attributes. Tributyrin also has negative organoleptic qualities, particularly high bitterness. These unpleasant taste and odor attributes can make oral administration of compositions containing these compounds particularly difficult, especially in the pediatric population.

[0008] It would therefore be beneficial to provide a food grade butyrate source with improved properties compared to available solutions. Liquid forms would provide further benefits due to ease of formulation and reduced solubility and homogenisation issues. Summary of the invention

[0009] The present invention provides compounds that are edible sources of butyrate. The present invention provides compounds with improved organoleptic properties. Specifically, the compounds have improved odor and / or taste relative to butyric acid, butyrate and tributyrin. The compounds can be used as a dietary source of butyric acid. The compounds can be used, for example, in nutritional compositions for human or animal consumption, including dietary supplements, medical foods, foods for special medical purposes, fortified foods, infant formulas and follow-on formulas.

[0010] Advantageously, the compounds of the present invention may provide efficient delivery of butyrate to the intestinal compartment.

[0011] According to a first aspect of the present invention, there is provided the use of a compound having the formula

[0012]

[0013] Where R 6 It is a long-chain fatty acid with 16 to 20 carbon atoms.

[0014] It is used in nutritional compositions to provide a dietary source of butyric acid or butyrate with improved organoleptic properties.

[0015] The compound of formula (1) may be present, for example, in a nutritional composition, such as a nutritional formulation, a fortified food, a medical food or a food for special medical purposes, a dietary supplement, an infant formula or a follow-on formula.

[0016] In one embodiment, the improved organoleptic property is improved smell. In one embodiment, the improved organoleptic property is improved taste. In one embodiment, the improved organoleptic property is improved smell and improved taste. In one embodiment, the improved taste is reduced bitterness.

[0017] According to one aspect of the present invention, there is provided a nutritional composition for providing a source of butyrate or butyric acid, the nutritional composition comprising a compound having the following formula as the main butyrate-containing triglyceride in the nutritional composition:

[0018]

[0019] Where R 6 It is a long-chain fatty acid with 16 to 20 carbons.

[0020] In a preferred embodiment, the compound of formula (1) is the major source of butyrate or butyric acid in the nutritional composition.

[0021] In one embodiment, the compound of formula (1) may provide at least 20%, at least 30%, at least 40%, at least 50%, or at least 60%, at least 70%, at least 80%, or at least 90% of the butyrate or butyric acid provided by the nutritional composition.

[0022] In one embodiment, the compound of formula (1) may provide at least 20 wt%, at least 30 wt%, at least 40 wt%, at least 50 wt%, or at least 60 wt%, at least 70 wt%, at least 80 wt%, or at least 90 wt% of the triglycerides containing the butyrate portion of the nutritional composition.

[0023] In another aspect, the compound of formula (1) provides at least 95% by weight, or substantially all, of the butyrate-containing portion of the triglycerides in the nutritional composition.

[0024] In one embodiment, the compound of formula (1) comprises at least 30 wt%, preferably at least 40 wt% of the total butyrate-containing triglycerides in the composition.

[0025] In a preferred embodiment, the compound of formula (1) comprises at least 50% by weight of the total butyrate-containing triglycerides in the composition.

[0026] In another preferred embodiment, the compound having formula (1) comprises at least 60% by weight of the total butyrate-containing triglycerides in the composition.

[0027] In one embodiment, the compound having formula (1) comprises at least 70% by weight of the total butyrate-containing triglycerides in the composition.

[0028] In one embodiment, the compound of formula (1) comprises at least 80% by weight of the total butyrate-containing triglycerides in the composition.

[0029] In one embodiment, the compound of formula (1) comprises at least 90% by weight of the total butyrate-containing triglycerides in the composition.

[0030] In one embodiment, the compound of formula (1) comprises at least 95% by weight of the total butyrate-containing triglycerides in the composition.

[0031] According to one aspect of the present invention, there is provided a nutritional composition for providing a source of butyrate or butyric acid, the nutritional composition comprising a compound having the formula

[0032]

[0033] Where R 6 is a long chain fatty acid having 16 to 20 carbon atoms, and optionally a compound of the formula

[0034]

[0035] Where R 1 is a long chain fatty acid having 16 to 20 carbons, wherein the compound of formula (1), optionally in combination with the compound of formula (2), is present in an amount of at least 30% by weight, preferably at least 40% by weight, more preferably at least 50% by weight of the total butyrate-containing triglycerides in the composition.

[0036] In one embodiment, the compound of formula (1) and the compound of formula (2) are present in a composition as defined herein (e.g. a nutritional composition, a dietary supplement, an infant formula or an follow-on formula), wherein the combination of the compound of formula (1) and the compound of formula (2) is present in an amount of at least 50 wt %, preferably at least 60 wt % of the total butyrate-containing triglycerides in the composition.

[0037] In another embodiment, the compound of formula (1) and the compound of formula (2) are present in a composition as defined herein (e.g., a nutritional composition, a dietary supplement, an infant formula or an follow-on formula), wherein the combination of the compound of formula (1) and the compound of formula (2) is present in an amount of at least 60%, at least 70%, at least 80% or at least 90% by weight of the total butyrate-containing triglycerides in the composition.

[0038] In one embodiment, the nutritional composition comprises: less than 15%, preferably less than 10% by weight of the total butyrate-containing triglycerides in the composition of a compound having the formula

[0039]

[0040] Less than 10% by weight of the total butyrate-containing triglycerides in the composition contain a compound of the formula

[0041]

[0042] Less than 10% by weight of the total butyrate-containing triglycerides in the composition contain a compound of the formula

[0043]

[0044] Where R 1 , R 2 , R3 , R 4 and R 5 Each is independently a long chain fatty acid having 16 to 20 carbons.

[0045] In one embodiment, the nutritional composition comprises less than 8 wt%, preferably less than 5 wt%, or less than 2 wt% of the compound having formula (2) based on the total butyrate-containing portion of triglycerides in the composition.

[0046] In a preferred embodiment, the nutritional composition comprises less than 15% by weight of the combination of the compound of formula (3) and the compound of formula (4) based on the total butyrate-containing portion of triglycerides in the composition.

[0047] In one embodiment, the nutritional composition comprises less than 8 wt%, preferably less than 5 wt%, or less than 2 wt% of the compound having formula (3) based on the total butyrate-containing portion of triglycerides in the composition.

[0048] In one embodiment, the nutritional composition comprises less than 8 wt%, preferably less than 5 wt%, or less than 2 wt% of the compound having formula (4) based on the total butyrate-containing portion of triglycerides in the composition.

[0049] In one embodiment, the nutritional composition may be selected from a dietary supplement, a fortified food, a medical food or food for special medical purposes, an infant formula, a follow-on formula.

[0050] According to one aspect of the present invention, a dietary supplement for providing a source of butyrate or butyric acid is provided, the dietary supplement comprising a compound having the following formula as the main source of butyrate or butyric acid in the dietary supplement

[0051]

[0052] Where R 6 It is a long-chain fatty acid with 16 to 20 carbons.

[0053] The dietary supplement may be in the form of, for example, capsules, tablets, sachets, liquids / oils or powders.

[0054] According to another aspect of the present invention, there is provided an infant formula or follow-on formula comprising as the major source of butyrate or butyric acid in the infant formula or follow-on formula a compound having the formula

[0055]

[0056] Where R 6 Independently a long chain fatty acid having 16 to 20 carbons.

[0057] According to another aspect of the present invention, there is provided the use of an infant formula or follow-on formula of the present invention for providing a butyrate or butyric acid source having improved organoleptic properties.

[0058] According to another aspect of the present invention, there is provided a nutritional composition comprising a compound having the formula as the main source of butyrate or butyric acid in the nutritional composition

[0059]

[0060] Where R 6 The invention relates to a long-chain fatty acid having 16 to 20 carbon atoms, and the nutritional composition is used for improving or maintaining gastrointestinal (GI) health.

[0061] According to another aspect of the present invention, there is provided a method for improving or maintaining gastrointestinal health in a patient, the method comprising administering to the patient an effective amount of a nutritional composition comprising a compound having the formula as the main source of butyrate or butyric acid in the nutritional composition

[0062]

[0063] Where R 6 It is a long-chain fatty acid with 16 to 20 carbons.

[0064] In a preferred embodiment, the compound of formula (1) is the major triglyceride component of the butyrate-containing moiety in the nutritional composition.

[0065] In one embodiment, the compound of formula (1) is used as defined herein, or is present in a composition as defined herein (e.g., a nutritional composition, a dietary supplement, an infant formula or an follow-on formula). Preferably, the compound of formula (1) is present in an amount of at least 2 wt %, preferably at least 3 wt %, such as about 3 wt % to 6 wt %, of the total triglycerides in the composition.

[0066] In one embodiment, the compound of formula (1) is used as defined herein or is present in a dietary supplement as defined herein in an amount of at least 5 wt %, preferably at least 10 wt %, such as at least 15 wt % or at least 20 wt % of the total triglycerides in the composition.

[0067] In another embodiment, the compound of formula (1) is used as defined herein, or is present in a composition as defined herein (e.g. a nutritional composition, a dietary supplement, an infant formula or an follow-on formula), wherein the compound of formula (1) is present in an amount of at least 20% by weight of the total butyrate-containing triglycerides in the composition.

[0068] In a preferred embodiment, the compound of formula (1) is used as defined herein, or is present in a composition as defined herein (e.g. a nutritional composition, a dietary supplement, an infant formula or an follow-on formula), wherein the compound of formula (1) is present in an amount of at least 30 wt. %, preferably at least 40 wt. %, or preferably at least 50 wt. % of the total butyrate-containing triglycerides in the composition.

[0069] In another embodiment, the compound of formula (1) is used as defined herein, or is present in a composition as defined herein (e.g. a nutritional composition, a dietary supplement, an infant formula or an follow-on formula), wherein the compound of formula (1) is present in an amount of at least 60 wt %, at least 70 wt %, at least 80 wt % or at least 90 wt % of the total butyrate-containing triglycerides in the composition.

[0070] In another embodiment, the compound of formula (1) is used as defined herein, or is present in a composition as defined herein (e.g. a nutritional composition, a dietary supplement, an infant formula or an follow-on formula), wherein the compound of formula (1) is present in an amount of at least 95% by weight of the total butyrate-containing triglycerides in the composition.

[0071] In one embodiment, R as defined herein 6 It is an unsaturated fatty acid, preferably a monounsaturated fatty acid.

[0072] In one embodiment, R as defined herein 6 Selected from the group consisting of oleic acid, palmitic acid, stearic acid or linoleic acid.

[0073] In a preferred embodiment, R as defined herein 6 For oleic acid.

[0074] In one embodiment, the compound having formula (1) is:

[0075]

[0076] According to another aspect of the present invention, there is provided a composition comprising a compound having the formula

[0077]

[0078] wherein the compound of formula (5) comprises at least 2 weight %, at least 3 weight %, at least 5 weight % or at least 10 weight % of the total triglycerides in the composition.

[0079] In one embodiment, the compound having formula (5) comprises at least 20% by weight of the total butyrate-containing triglycerides in the composition.

[0080] In one embodiment, the compound having formula (5) comprises at least 30% by weight of the total butyrate-containing triglycerides in the composition.

[0081] In one embodiment, the compound of formula (5) comprises at least 40% by weight of the total butyrate-containing triglycerides in the composition.

[0082] In one embodiment, the compound having formula (5) comprises at least 50% by weight of the total butyrate-containing triglycerides in the composition.

[0083] In one embodiment, the compound having formula (5) comprises at least 60% by weight of the total butyrate-containing triglycerides in the composition.

[0084] In one embodiment, the compound of formula (5) comprises at least 70% by weight of the total butyrate-containing triglycerides in the composition.

[0085] In one embodiment, the compound of formula (5) comprises at least 80% by weight of the total butyrate-containing triglycerides in the composition.

[0086] In one embodiment, the compound having formula (5) comprises at least 90% by weight of the total butyrate-containing triglycerides in the composition.

[0087] In one embodiment, the compound having formula (5) comprises at least 95% by weight of the total butyrate-containing triglycerides in the composition.

[0088] In one embodiment, the compound of formula (5) comprises from about 20% to about 95% by weight of the total butyrate-containing triglycerides in the composition, from about 30% to about 95% by weight, from about 40% to about 90% by weight, from about 50% to about 90% by weight, or from about 60% to about 95% by weight of the total butyrate-containing triglycerides in the composition.

[0089] In one embodiment, the compound of formula (5) comprises from about 40% to about 80% by weight of the total butyrate-containing triglycerides in the composition, such as from about 50% to about 70% by weight of the total butyrate-containing triglycerides in the composition.

[0090] In one embodiment, the compound of formula (5) comprises from about 50% to about 90% by weight of the total butyrate-containing triglycerides in the composition, such as from about 60% to about 80% by weight of the total butyrate-containing triglycerides in the composition.

[0091] According to one aspect of the present invention, there is provided a nutritional composition for providing a source of butyrate or butyric acid, the nutritional composition comprising a compound having the formula (5) and optionally a compound of the following formula

[0092]

[0093] The compound of formula (5), optionally in combination with the compound of formula (6), is present in an amount of at least 30 wt%, preferably at least 40 wt%, more preferably at least 50 wt% of the total butyrate-containing triglycerides in the composition.

[0094] In one embodiment, the compound of formula (5) and the compound of formula (6) are present in a composition as defined herein (e.g. a nutritional composition, a dietary supplement, an infant formula or an follow-on formula), wherein the combination of the compound of formula (5) and the compound of formula (6) is present in an amount of at least 50 wt %, preferably at least 60 wt % of the total butyrate-containing triglycerides in the composition.

[0095] In another embodiment, the compound of formula (5) and the compound of formula (6) are present in a composition as defined herein (e.g., a nutritional composition, a dietary supplement, an infant formula or an follow-on formula), wherein the combination of the compound of formula (5) and the compound of formula (6) is present in an amount of at least 60%, at least 70%, at least 80% or at least 90% by weight of the total butyrate-containing triglycerides in the composition.

[0096] In one embodiment, the composition comprises less than 10% by weight of the total butyrate-containing triglycerides in the composition of a compound having the formula

[0097]

[0098] According to one embodiment, the composition comprises less than 10% by weight of the total butyrate-containing triglycerides in the composition of a compound having the formula

[0099]

[0100] According to one embodiment, the composition comprises less than 10% by weight of the total butyrate-containing triglycerides in the composition of a compound having the formula

[0101]

[0102] In one embodiment, the nutritional composition comprises less than 8 wt%, preferably less than 5 wt%, or less than 2 wt% of the compound having formula (6) based on the total butyrate-containing portion of triglycerides in the composition.

[0103] In a preferred embodiment, the nutritional composition comprises less than 15% by weight of the combination of the compound of formula (7) and the compound of formula (8) based on the total butyrate-containing portion of triglycerides in the composition.

[0104] In one embodiment, the nutritional composition comprises less than 8 wt%, preferably less than 5 wt%, or less than 2 wt% of the compound having formula (7) based on the total butyrate-containing portion of triglycerides in the composition.

[0105] In one embodiment, the nutritional composition comprises less than 8 wt%, preferably less than 5 wt%, or less than 2 wt% of the compound having formula (8) based on the total butyrate-containing portion of triglycerides in the composition.

[0106] The composition of the present invention may also include: 1,3-dibutyryl-2-linoleoyl glycerol, 1,3-dibutyryl-2-stearoyl glycerol, 1-butyryl-2-oleoyl-3-palmitoyl glycerol, 1-palmitoyl-2-oleoyl-3-butyryl glycerol, 1-butyryl-2-oleoyl-3-linoleoyl glycerol, 1-linoleoyl-2-oleoyl-3-butyryl glycerol, 1-oleoyl-2-butyryl-3-linoleoyl glycerol, 1-linoleoyl-2-butyryl-3-oleoyl glycerol, 1-butyryl-2-linoleoyl- 3-oleoyl glycerol, 1-oleoyl-2-linoleoyl-3-butyryl glycerol, 1-butyryl-2-stearoyl-3-oleoyl glycerol, 1-oleoyl-2-stearoyl-3-butyryl glycerol, 1-butyryl-2-oleoyl-3-stearoyl glycerol, 1-stearoyl-2-oleoyl-3-butyryl glycerol, 1,2-dioleoyl-3-palmitoyl glycerol, 1-palmitoyl-2,3-dioleoyl glycerol, 1,2-dioleoyl-3-linoleoyl glycerol and / or 1-linoleoyl-2,3-dioleoyl glycerol.

[0107] The composition of the present invention is preferably in the form of a nutritional composition.

[0108] The composition of the present invention may be in the form of an infant formula or a follow-on formula.

[0109] The composition of the present invention may be in the form of a dietary supplement.

[0110] According to another aspect of the present invention there is provided the use of a composition as defined herein for providing a butyrate or butyric acid source having improved organoleptic properties.

[0111] According to another aspect of the present invention, there is provided a method of providing a source of butyrate having improved organoleptic properties to an individual, the method comprising administering to the individual an effective amount of a composition as defined herein.

[0112] According to another aspect of the present invention there is provided a composition as defined herein for use in improving or maintaining gastrointestinal health.

[0113] According to another aspect of the present invention, there is provided a method of improving or maintaining gastrointestinal health in an individual, the method comprising administering to the individual an effective amount of a composition as defined herein. DETAILED DESCRIPTION

[0114] Triglycerides

[0115] Triglycerides (also called triacylglycerols) are triesters derived from glycerol and three fatty acids.

[0116] Fatty acids are carboxylic acids with a long tail (chain). Fatty acids can be unsaturated or saturated. Fatty acids that are not attached to other molecules are called free fatty acids (FFA).

[0117] The term "fatty acid moiety" refers to the portion of a triglyceride produced from a fatty acid in an esterification reaction with glycerol. The triglyceride used in the present invention comprises two butyric acid moieties (also referred to as "butyrate moieties") and one long-chain fatty acid moiety.

[0118] Advantageously, the compounds and compositions of the present invention can provide high butyric acid content by optimizing the butyric acid content of triglycerides while exhibiting improved organoleptic properties compared to tributyrin.

[0119] Preferred long chain fatty acids for use in the present invention are fatty acids having 16 to 20 carbon atoms.

[0120] Examples of long-chain fatty acids include oleic acid, palmitic acid, stearic acid, and linoleic acid.

[0121] The preferred long chain fatty acid used in the present invention is oleic acid. Oleic acid is the main fatty acid present in breast milk.

[0122] The triglyceride of the present invention can be synthesized by, for example, esterification of long-chain fatty acid monoacylglycerol (MAG) with butyric acid.

[0123] The triglyceride of the present invention can be synthesized by, for example, esterification of long-chain fatty acid monoacylglycerol (MAG) with butyric acid (BA) with the removal of water. By way of example, a method for obtaining 1,2-dibutyryl-3-oleoyl glycerol is as follows:

[0124]

[0125] The esterification reaction is preferably carried out with a butyric acid (BA): monoacylglycerol (MAG) molar ratio of ≥2; ie a molar excess of butyric acid, for example a BA:MAG molar ratio of about 3.

[0126] Removal of water may be carried out by conventional methods routinely determined by one skilled in the art.

[0127] Advantageously, such synthetic methods avoid the use of tributyrin as a starting material.

[0128] Alternative triglyceride synthesis methods can be routinely determined by one skilled in the art.

[0129] In one embodiment, sunflower oil is the source of monoolein as monoacylglycerol. This produces triglycerides containing mainly butyrate and oleate moieties.

[0130] These compounds are dairy-free, cholesterol-free and vegan. The fatty acids are liberated from the triglycerides due to lipases naturally present in the gastrointestinal tract. Relative to butyrate, these compounds do not add additional mineral salts to the final formula.

[0131] Triglycerides containing a single butyrate moiety may be used herein. Alternatively, mixtures of triglycerides containing different butyrate moieties may be used.

[0132] The triglycerides may also be subjected to decolorization and / or deodorization steps conventional in the art and well known to those skilled in the art, for example as conventionally used in the manufacture of vegetable oils.

[0133] Composition

[0134] The present invention provides a composition comprising a triglyceride containing a butyrate moiety as mentioned herein. The composition can be, for example, a nutritional composition, including a fortified food, a medical food or a food for special medical purposes, a dietary supplement, an infant formula or an follow-on formula.

[0135] The expression "nutritional composition" refers to a composition that supplies nutrients to an individual. Such a nutritional composition is preferably orally administered and may comprise a lipid or fat source and a protein source. It 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 may comprise a lipid (or fat) source and a protein source, a carbohydrate source, or both.

[0136] In some embodiments, the nutritional composition according to the present invention is a food for special dietary uses (FSDU). As used herein, the expression "food for special dietary uses" refers to a food material specially formulated to meet specific dietary needs due to specific physical or physiological conditions and / or specific diseases and disorders (e.g. CODEX STAN 146-1985, Section 2.1).

[0137] In some specific embodiments, the nutritional composition according to the present invention is a medical food or a food for special medical purposes (FSMP). As used herein, "medical food" or "food for special medical purposes" refers to a food specially formulated and intended for the dietary management of a disease. In the U.S., "medical food" is defined in Section 5 (b) of the U.S. Food and Drug Administration's 1988 Orphan Drug Act (Orphan Drug Act) (21 U.S.C. 360ee (b) (3)). In Europe, "medical food" is referred to as "food for special medical purposes" (e.g., as defined under European Commission Delegated Regulation (EU) 2016 / 128 on September 25, 2015). The terms "medical food" and "food for special medical purposes" are used interchangeably herein.

[0138] In some embodiments, the nutritional composition according to the invention is an "enteral nutritional composition", i.e., it involves a food material to be administered in the gastrointestinal tract. Gastric introduction may involve the use of a tube passed through the oral / nasal passages or a tube in the abdomen directly to the stomach. This may be used in particular in a hospital or clinic.

[0139] The composition according to the invention may be an infant formula (eg a first stage infant formula), a second stage or follow-on formula, a growing-up milk, a baby food, an infant cereal composition, a fortifier (such as a human milk fortifier) ​​or a supplement.

[0140] The expression "infant formula" as used herein means a food intended for the nutrition of infants in the first few months of life and which meets the multiple nutritional requirements of such persons (e.g. in accordance with Article 2(c) of Council Directive 91 / 321 / EEC 2006 / 141 / EC of 22 December 2006 on infant formula and follow-on formula).

[0141] Generally speaking, stage 1 infant formula is used as a breast milk substitute for infants from birth. Stage 2 or follow-on infant formula is provided from the 6th month onwards. Infant formula constitutes the main liquid element in the gradually diversified diet of such people. "Growing-up milk" (or GUM) is provided from the age of one year. It is usually a milk-containing beverage adapted to the specific nutritional needs of young children.

[0142] The term "fortifier" relates 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 breast milk or mother's colostrum, or donor's breast milk or donor's colostrum.

[0143] The term "dietary supplement" can be used to supplement an individual's nutrition (it is usually used as such, but it can also be added to any kind of composition intended for ingestion). The supplement can be in tablet, capsule, lozenge or liquid form, for example. The supplement can also contain protective hydrophilic colloids (such as gums, proteins, modified starches), binders, film formers, encapsulating agents / materials, wall / shell materials, matrix compounds, coatings, emulsifiers, surfactants, solubilizers (oils, fats, waxes, lecithins, etc.), adsorbents, carriers, fillers, co-compounds, dispersants, wetting agents, processing aids (solvents), flow agents, taste masking agents, weighting agents, gelling 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 from any source, vegetable gums, lignin sulfonates, talc, sugars, starches, gum arabic, vegetable oils, polyalkylene glycols, flavors, preservatives, stabilizers, emulsifiers, buffers, lubricants, colorants, wetting agents, fillers, etc.

[0144] In another specific embodiment, the nutritional composition of the present invention is a fortifier. The fortifier can be a breast milk fortifier or a formula fortifier, such as an infant formula fortifier. Therefore, when the infant or toddler is premature, the fortifier is a particularly advantageous embodiment.

[0145] When the composition is a supplement, it may be provided in unit dosage form.

[0146] The nutritional composition of the present invention, especially infant formula, typically comprises a protein source, a carbohydrate source and a lipid source. However, in some embodiments, particularly if the nutritional composition of the present invention is a supplement or fortifier, only lipid (or lipid source) may be present.

[0147] The nutritional composition according to the present invention may contain a protein source. The amount of protein may be 1.6 g / 100 kcal to 3 g / 100 kcal. In some embodiments, particularly when the composition is used for premature infants / young children, the amount of protein may be 2.4 g / 100 kcal to 4 g / 100 kcal or higher than 3.6 g / 100 kcal. In some other embodiments, the amount of protein may be less than 2.0 g / 100 kcal, for example, 1.8 g / 100 kcal to 2 g / 100 kcal, or less than 1.8 g / 100 kcal.

[0148] Protein sources based on, for example, whey, casein and mixtures thereof can be used, as well as plant-based (e.g., soy-based) protein sources. With regard to whey protein of interest, the protein source can be based on acid whey or sweet whey or a mixture thereof, and can contain alpha-lactalbumin and beta-lactoglobulin in any desired proportion. In some embodiments, the protein source is mainly whey (i.e., more than 50% of the protein comes from whey protein, such as 60%> or 70%>). The protein can be intact or hydrolyzed, or a mixture of intact protein and hydrolyzed protein. The so-called term "intact" means that the main part of the protein is intact, i.e., the molecular structure has not changed, for example, at least 80% of the protein has not changed, such as at least 85% of the protein has not changed, preferably at least 90% of the protein has not changed, even more preferably at least 95% of the protein has not changed, such as at least 98% of the protein has not changed. In a specific embodiment, 100% of the protein has not changed.

[0149] The term "hydrolyzed" means in the context of the present invention that a protein has been hydrolyzed or broken down into its constituent amino acids.

[0150] The protein may be fully hydrolyzed or partially hydrolyzed. If hydrolyzed protein is desired, a hydrolysis process may be performed as desired and as known in the art. For example, a whey protein hydrolyzate may be prepared by enzymatic hydrolysis of the whey fraction in one or more steps. If the whey fraction used as a raw material is substantially lactose-free, it is found that the protein undergoes much less lysine blockage during the hydrolysis process. This makes it possible to reduce the degree of lysine blockage 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.

[0151] In a specific 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, 8 to 40, or 20 to 60, or 20 to 80, or greater than 10, 20, 40, 60, 80 or 90. For example, a nutritional composition containing a hydrolyzate with a degree of hydrolysis of less than about 15% may be obtained from Nestle Company under the trademark Commercially available.

[0152] At least 70%, 80%, 85%, 90%, 95% or 97% of the protein may be hydrolyzed. In a particular embodiment, 100% of the protein is hydrolyzed.

[0153] In a specific embodiment, the protein of the composition is a plant-based protein.

[0154] The nutritional composition according to the present invention may include 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 present in infant formula, such as lactose, sucrose, sucrose, maltodextrin, starch and mixtures thereof, may be used, but one of the preferred carbohydrate sources of infant formula is lactose. The nutritional composition of the present invention may also contain all vitamins and minerals that are considered necessary for daily diet and in significant amounts of nutrition. The minimum requirements of certain vitamins and minerals have been determined. Examples of minerals, vitamins and other nutrients optionally present in the composition 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 the form of salts. The presence and amount of specific minerals and other vitamins will vary depending on the target group. If necessary, the nutritional composition of the present invention may contain emulsifiers and stabilizers, such as soy, lecithin, citric acid monoglyceride and citric acid diglyceride, etc. The nutritional composition of the present invention may also contain other substances that may have beneficial effects, such as lactoferrin, osteopontin, TGFbeta, slgA, glutamine, nucleotides, nucleosides, etc.

[0155] The composition of the present invention may also comprise at least one non-digestible oligosaccharide (eg prebiotic), typically in an amount of 0.3% to 10% by weight of the composition.

[0156] Prebiotics are generally non-digestible in the sense that they are not broken down and absorbed in the stomach or small intestine, and thus they can remain intact as they pass through the stomach and small intestine to the colon, where they are selectively fermented by beneficial bacteria. Examples of prebiotics include certain oligosaccharides, such as fructooligosaccharides (FOS), inulin, xylooligosaccharides (XOS), polydextrose, or any mixture thereof. In a specific embodiment, the prebiotic may be fructooligosaccharides and / or inulin. In a specific embodiment, the prebiotic is a combination of FOS and inulin, such as in the product sold by BENEO-Orafti under the trademark Fructo-oligosaccharides (formerly ) or sold by BENEO-Orafti under the trademark Inulin (formerly ). Another example is the combination of 70% short chain oligofructose and 30% inulin, which is registered by Nestle under the trademark "Prebio 1". The nutritional composition of the present invention may also include at least one milk oligosaccharide, which may be a BMO (bovine milk oligosaccharide) and / or an HMO (human milk oligosaccharide). The composition of the present invention may also include at least one probiotic (or probiotic strain), such as a probiotic bacterial strain.

[0157] The most commonly used probiotic microorganisms are mainly most bacteria and yeasts of the following genera: Lactobacillus spp., Streptococcus spp., Enterococcus spp., Bifidobacterium spp. and Saccharomyces spp.

[0158] In some embodiments, the probiotic is a probiotic bacterial strain. In some embodiments, it is a bifidobacterium and / or a lactobacillus.

[0159] Based on dry weight, the nutritional composition according to the invention may comprise 10e3 to 10e12 cfu of the probiotic strain, more preferably 10e7 to 10e12 cfu (such as 10e8 to 10e10 cfu) of the probiotic strain per g of composition.

[0160] In one embodiment, the probiotic is live. In another embodiment, the probiotic is non-replicating or inactivated. It can also be a probiotic part, such as a cell wall component or a product of probiotic metabolism. In some other embodiments, live probiotics and inactivated probiotics can exist simultaneously. The nutritional composition of the present invention may also include at least one bacteriophage (bacteriophage) or a mixture of bacteriophages, which are preferably directed against pathogenic Streptococci, Haemophilus, Moraxella and Staphylococcus.

[0161] In one embodiment, the nutritional composition according to the present invention may be a dairy product. A dairy product is a product comprising a milk-based product. Dairy products are generally prepared from a suitable mixture of concentrated milk protein and a fat source. Dairy products may be acidified. Dairy products include ready-to-drink milk-containing beverages, concentrated milk, condensed milk, sweetened condensed milk, milk powder, yogurt, fresh cheese, cheese, ice cream, and dairy spreads, such as spreadable fresh cheese, cottage cheese, quark cheese, French cream, clotted cream and cream cheese. Milk powder can be manufactured, for example, by spray drying or by freeze drying.

[0162] Depending on their fat content, dairy products can be prepared from whole 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. Typically, whole milk is milk containing 3% to 4% fat. The exact fat content of skimmed milk, semi-skimmed milk and whole milk depends mainly on local food regulations.

[0163] Dairy products are usually made from cow's milk. Dairy products can also be made from buffalo milk, yak milk, goat milk, ewe milk, mare milk, donkey milk, camel milk, reindeer milk, moose milk or a combination thereof.

[0164] Acidified dairy products can be obtained by fermentation with suitable microorganisms. Fermentation provides flavor and acidity to dairy products. It can also affect the texture of dairy products. In addition, the microorganisms used for fermentation are selected according to the ability of the microorganism to ferment milk into edible fermented dairy products. Generally, the microorganisms are known for their beneficial properties. The microorganisms include lactic acid bacteria and yeast. Some of these microorganisms can be considered as probiotics. The example of lactic acid bacteria includes Lactobacillus delbrueckii subsp.bulgaricus and Streptococcus thermophilus, both of which are related to the production of yogurt, or other lactic acid bacteria belonging to the genus Lactobacillus, Streptococcus, Lactococcus, Leuconostoc, Bifidobacterium, Pediococcus or any mixture thereof.

[0165] Another example of a fermented dairy product (also called cultured dairy product or cultured dairy or cultured milk) is cultured buttermilk fermented with Lactococcus lactis (Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactis biovar. diacetylactis) and / or Leuconostoc mesenteroides subsp. cremoris.

[0166] The microorganisms may be live or inactivated.

[0167] Dairy analogs are products prepared in a similar manner to the above-mentioned dairy products, but using (wholly or partially) non-dairy sources of protein and / or (wholly or partially) non-dairy sources of edible fat. Suitable protein sources include vegetable proteins such as soy, potato and pea. Suitable fat sources include oils and fats from plant or marine sources. Fats and oils are used as interchangeable terms. The similar preparations mentioned above are intended to include methods for products in which the traditional whey separation step is omitted because the formulation of the dairy analogs of the product allows this step to be skipped.

[0168] The nutritional composition according to the invention may be prepared in any suitable way.

[0169] For example, formula foods such as infant formula foods can be prepared by blending a protein source, a carbohydrate source, and a fat source in an appropriate ratio. If used, an emulsifier can be added at this time. Vitamins and minerals can be added at this time, but they are usually added later to avoid thermal degradation. Before blending, any lipophilic vitamins, emulsifiers, etc. can be dissolved in a fat source. Water (preferably water subjected to reverse osmosis) can then be mixed to form a liquid mixture. The water temperature is suitably in the range of about 50°C to about 80°C to help disperse the ingredients. A commercially available liquefier can be used to form a liquid mixture.

[0170] Particularly if the final product is in liquid form, any oligosaccharides may be added at this stage. If the final product is a powder, these ingredients may also be added at this stage if desired.

[0171] The liquid mixture is then homogenized, for example in two stages.

[0172] In one embodiment, the nutritional composition of the invention is administered to an infant or young child as a supplementary composition to breast milk.

[0173] The composition of the invention may be in the form of, for example, a solid (eg, powder), a liquid or a gel.

[0174] The composition of the present invention may be in the form of, for example, tablets, dragees, capsules, pellets, powders, granules, solutions, emulsions, suspensions, coated granules, spray-dried granules or pills.

[0175] The composition may be in the form of a pharmaceutical composition and may contain one or more suitable pharmaceutically acceptable carriers, diluents and / or excipients.

[0176] Examples of such suitable excipients for the compositions described herein may be found in "Handbook of Pharmaceutical Excipients", 2nd Edition, (1994), Edited by A Wade and PJ Weller.

[0177] Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (AR Gennaro, ed., 1985).

[0178] The pharmaceutical composition may contain the following substances as carriers, excipients or diluents or in addition to carriers, excipients or diluents: any suitable binder, lubricant, suspending agent, coating agent and / or solubilizer. Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flowing lactose, beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium alginate, carboxymethylcellulose and polyethylene glycol.

[0179] Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like.

[0180] Preservatives, stabilizers, dyes and even flavoring agents may be provided in the composition. Examples of preservatives include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may also be used.

[0181] Gastrointestinal health

[0182] The compounds defined herein are sources of butyrate / butyric acid and are therefore useful for improving or maintaining gastrointestinal (GI) health.

[0183] In one embodiment, the compounds and compositions defined herein may be used to treat inflammatory bowel disease, such as Crohn's disease or ulcerative colitis.

[0184] The multiple beneficial effects of butyrate on GI health are well documented. At the intestinal level, butyrate modulates transepithelial fluid transport, mucosal inflammation and oxidative status, strengthens the epithelial barrier, and regulates visceral sensitivity and intestinal motility.

[0185] Fatty acids, including butyrate, are the main energy source for colonic mucosal cells (Roedriger, Gut. 1980; 21: 793-798), and are most important for colonocytes in the distal region of the colon. A strong nutritional 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 concentrations leads to atrophy of the colonic mucosa, which is generally explained by a decrease in the utilization of substrates by colonocytes. On the other hand, the administration of butyrate into the colonic lumen leads to weight gain, increased DNA synthesis, and increased intestinal crypt depth (Kripke et al., J Parenter Enter Nutr. 1989; 13: 109-116).

[0186] High concentrations of butyrate obtained by fermentation of insoluble dietary fiber or after anal administration of butyrate can inhibit early and late stages of colon carcinogenesis by regulating the transcription, expression and activation of key proteins of the apoptotic cascade (Avivi-Green et al., J Nutr. 2002; 132(7): 1812-18).

[0187] Chapman et al. (Gut 1994; 35(1):73-76) showed that inflamed colonic mucosa captures much more butyrate than glutamine or glucose. Experiments have shown that butyrate infusion leads to a significant reduction in inflammation and a reduction in the extent of colonic wall ulceration in rats (Andoh et al., J Parenter Enter Nutr. 1999; 23(5):70-73).

[0188] The effectiveness of butyrate enemas has been demonstrated clinically 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).

[0189] The direct anti-inflammatory activity of butyrate may be related to the inhibition of the migration of nuclear factor Kappa B (NFKB) and its binding to DNA, and for the same reason, it may also be related to the inhibition of the transcription and production of pro-inflammatory cytokines (Segain et al., Gut. 2000; 47: 397-403).

[0190] Therefore, the triglyceride compounds used in the present invention are a source of butyrate, which can play an important role in maintaining intestinal homeostasis and GI health.

[0191] Application

[0192] Preferably, the compounds and compositions described herein are administered enterally.

[0193] Enteral administration may be, for example, oral or gastric administration.

[0194] Generally, administration of the combinations or compositions described herein may be, for example, by the oral route or another route into the gastrointestinal tract, such as by tube feeding.

[0195] The subject may be a mammal, such as a human, canine, feline, equine, caprine, bovine, ovine, porcine, cervidae, and primate. Preferably, the subject is a human.

[0196] Various embodiments of the present invention include the following.

[0197] 1. A nutritional composition for providing a source of butyrate or butyric acid, the nutritional composition comprising a compound having the following formula as the main butyrate-containing triglyceride in the nutritional composition

[0198]

[0199] Where R 6 It is a long-chain fatty acid with 16 to 20 carbons.

[0200] 2. The nutritional composition according to embodiment 1, wherein the compound of formula (1) is the main source of butyrate or butyric acid in the nutritional composition.

[0201] 3. The nutritional composition of embodiment 1 or 2, wherein the compound of formula (1) provides at least 20%, at least 30%, at least 40%, at least 50%, or at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or substantially all of the butyrate-containing portion of triglycerides provided by the nutritional composition.

[0202] 4. The nutritional composition according to any one of embodiments 1 to 3, wherein the nutritional composition is a dietary supplement for providing a source of butyrate.

[0203] 5. The dietary supplement according to embodiment 4, which is in the form of capsules, liquids, tablets, sachets or powders.

[0204] 6. The nutritional composition according to any one of embodiments 1 to 3, wherein the nutritional composition is in the form of an infant formula or a follow-on formula.

[0205] 7. The nutritional composition according to any one of embodiments 1 to 5, for use in improving or maintaining gastrointestinal (GI) health.

[0206] 8. Use of a compound of the formula

[0207]

[0208] Where R 6 It is a long chain fatty acid having 16 to 20 carbons, wherein the compound of formula (1) is the main triglyceride containing butyrate part in the nutritional composition.

[0209] 9. The use according to embodiment 8, wherein the nutritional composition is selected from a fortified food, a medical food or a food for special medical purposes, a food for special dietary purposes, a dietary supplement, an infant formula or an follow-on formula.

[0210] 10. The nutritional composition according to any one of embodiments 1 to 6, the compound for use according to embodiment 7, or the use according to any one of embodiments 8 to 9, wherein the compound of formula (1) is present in the composition comprising the compound of formula (1) in an amount of at least 3% by weight of the total triglycerides in the composition.

[0211] 11. The nutritional composition according to any one of embodiments 1 to 6, the compound for use according to embodiment 7 or the use according to any one of embodiments 8 to 9, wherein the compound of formula (1) is present in the composition comprising the compound of formula (1) in an amount of at least 30% by weight of the total butyrate-containing triglycerides in the composition, preferably at least 50% by weight of the total butyrate-containing triglycerides in the composition.

[0212] 12. The nutritional composition according to any one of embodiments 1 to 5, the compound for use according to embodiment 7, or the use according to any one of embodiments 8 to 9, wherein the compound of formula (1) is present in the composition comprising the compound of formula (1) in an amount of at least 60%, at least 70%, at least 80% or at least 90% by weight of the total butyrate-containing triglycerides in the composition.

[0213] 13. The nutritional composition according to any one of embodiments 1 to 6 or 10 to 12, the compound for use according to embodiments 7 or 10 to 12, or the use according to any one of embodiments 8 to 9 or 10 to 12, wherein R 6 Selected from the group consisting of oleic acid, palmitic acid or linoleic acid.

[0214] 14. A nutritional composition comprising a compound having the formula

[0215]

[0216] wherein the compound of formula (5) comprises at least 20% by weight of the total butyrate-containing triglycerides in the composition.

[0217] 15. The nutritional composition according to embodiment 14, wherein the compound of formula (5) comprises at least 3 weight % of the total triglycerides in the nutritional composition.

[0218] 16. The nutritional composition according to embodiment 14 or 15, wherein the compound of formula (5) comprises at least 30 wt.%, at least 40 wt.%, preferably at least 50 wt.% of the total butyrate-containing triglycerides in the composition.

[0219] 17. The nutritional composition according to embodiment 16, wherein the compound of formula (5) accounts for at least 60 wt.%, at least 70 wt.%, preferably at least 80 wt.% of the total butyrate-containing triglycerides in the composition.

[0220] 18. The composition of any one of embodiments 14 to 17, wherein the composition is an infant formula, a follow-on formula, or a dietary supplement.

[0221] 19. Use of a composition according to any one of embodiments 14 to 18 for providing a butyrate source with improved organoleptic properties.

[0222] 20. The composition according to any one of embodiments 14 to 19, for use in improving or maintaining gastrointestinal health.

[0223] Example

[0224] Example 1 - Preparation of triglycerides containing butyrate moieties

[0225] The composition comprising triglycerides containing butyrate moieties is generated by the esterification reaction between monoolein (derived from sunflower oil) and butyric acid added in a molar excess (5 equivalents in total). The two reagents are mixed together in a flask and heated to reflux (butyric acid boiling point is 163.5°C). A condenser ("colonne de Vigreux") is used to remove water. The reaction is monitored by TLC and stopped when all monoacylglycerols are converted to triacylglycerols.

[0226] The components of the resulting oil composition (primarily 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: butyrate is 4:0, palmitate is 16:0, stearate is 18:0, oleate is 18:1, and linoleate is 18:2. The middle fatty acid is located at the sn-2 position in the triglyceride. For example, 16:0-4:0-18:1 represents two different triglycerides that have both sn-2 butyrate and sn-1 palmitate and sn-3 oleate or sn-1 oleate and sn-3 palmitate.

[0227] Table 1: Triglyceride distribution [wt %]

[0228]

[0229]

[0230] In this composition, 4:0-4:0-18:1 was identified as the most abundant triglyceride.

[0231] The resulting oil product is then subjected to a decolorization step under the action of bleaching earth and purified by short-path distillation (130° C., 0.001-0.003 mbar) and / or by deodorization by injection of steam water (160° C., 2 mbar, 2 hours) to remove residual reagents and intermediates such as butyric acid, MAG and by-products such as DAG and tributyrin.

[0232] The resulting oil product was evaluated in a descriptive sensory evaluation and was found to have a better smell and taste than tributyrin and butyric acid.

Claims

1. Provide a use of a nutritional composition of butyrate or butyric acid source in the preparation of a medicament for treating inflammatory bowel disease, Crohn's disease or ulcerative colitis, wherein the nutritional composition comprises a compound having the following formula as the main triglyceride containing butyrate part in the nutritional composition Where R 6 It is a long-chain fatty acid with 16 to 20 carbons.

2. Use of a nutritional composition according to claim 1, wherein the compound of formula (1) is the main source of butyrate or butyric acid in the nutritional composition.

3. Use of a nutritional composition according to claim 1 or 2, wherein the compound of formula (1) provides at least 20%, at least 30%, at least 40%, at least 50%, or at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or substantially all of the butyrate-containing triglyceride provided by the nutritional composition.

4. Use of the nutritional composition according to any one of claims 1 to 3, wherein the nutritional composition is a dietary supplement for providing a source of butyrate.

5. The dietary supplement according to claim 4, which is in the form of capsules, liquids, tablets, sachets or powders.

6. Use of a nutritional composition according to any one of claims 1 to 3, wherein the nutritional composition is in the form of an infant formula or a follow-on formula.

7. Use of a compound of the formula Where R 6 It is a long chain fatty acid having 16 to 20 carbons, wherein the compound of formula (1) is the main triglyceride containing butyrate part in the nutritional composition.

8. Use of a compound according to claim 7, wherein the nutritional composition is selected from a fortified food, a medical food or a food for special medical purposes, a food for special dietary purposes, a dietary supplement, an infant formula or an follow-on formula.

9. Use of a nutritional composition according to any one of claims 1 to 6 or use of a compound according to claim 7 or 8, wherein the compound of formula (1) is present in the composition comprising the compound of formula (1) in an amount of at least 3% by weight of the total triglycerides in the composition.

10. Use of a nutritional composition according to any one of claims 1 to 6 or use of a compound according to claim 7 or 8, wherein the compound of formula (1) is present in the composition comprising the compound of formula (1) in an amount of at least 30% by weight of the total butyrate-containing triglycerides in the composition, preferably at least 50% by weight of the total butyrate-containing triglycerides in the composition.

11. Use of a nutritional composition according to any one of claims 1 to 5 or use of a compound according to claim 7 or 8, wherein the compound of formula (1) is present in the composition comprising the compound of formula (1) in an amount of at least 60%, at least 70%, at least 80% or at least 90% by weight of the total butyrate-containing triglycerides in the composition.

12. Use of a nutritional composition according to any one of claims 1 to 5 or 9 to 11 or use of a compound according to any one of claims 7 to 11, wherein R 6 Selected from the group consisting of oleic acid, palmitic acid or linoleic acid.

13. Use of a nutritional composition for the preparation of a medicament for treating inflammatory bowel disease, Crohn's disease or ulcerative colitis, the nutritional composition comprising a compound having the formula wherein the compound of formula (5) comprises at least 20% by weight of the total butyrate-containing triglycerides in the composition.

14. Use of a nutritional composition according to claim 13, wherein the compound of formula (5) represents at least 3% by weight of the total triglycerides in the nutritional composition.

15. Use of a nutritional composition according to claim 13 or 14, wherein the compound of formula (5) represents at least 30 wt.%, at least 40 wt.%, preferably at least 50 wt.% of the total butyrate-containing triglycerides in the composition.

16. Use of a nutritional composition according to claim 15, wherein the compound of formula (5) represents at least 60%, at least 70%, preferably at least 80% by weight of the total butyrate-containing triglycerides in the composition.

17. Use of a composition according to any one of claims 13 to 16, wherein the composition is an infant formula, a follow-on formula or a dietary supplement.

18. Use of a composition according to any one of claims 13 to 17 for providing a butyrate source with improved organoleptic properties.

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