Composition for controlling proliferation of butyrate-producing bacteria, composition for controlling butyrate production, composition for controlling proliferation of bacteria of the genus bifidobacterium, and uses of same
A composition of sugar alcohols and derivatives effectively controls butyric acid-producing bacteria and production, enhancing intestinal health benefits by promoting beneficial bacterial growth and production, addressing the limitations of existing technologies.
Patent Information
- Application Number
- PCT/JP2025/014945
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-04-26
- Filing Date
- 2025-04-16
- Publication Date
- 2025-10-30
AI Technical Summary
Existing technologies do not effectively control the growth of butyric acid-producing bacteria and butyric acid production, and there is a demand for prebiotic materials with improved functionality and physical properties to enhance health benefits associated with butyric acid production in the intestine.
A composition comprising sugar alcohols and their derivatives, particularly maltitol, inositol, xylitol, and erythritol, is used to control the growth and production of butyric acid-producing bacteria, including those belonging to the genera Anaerostipes and Eubacterium, and promote the growth of Bifidobacterium bacteria, enhancing intestinal health benefits.
The composition effectively regulates the growth and production of butyric acid-producing bacteria, improving intestinal peristalsis, suppressing inflammation, and enhancing immunity, while ensuring safety and compliance with food safety laws.
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Abstract
Description
Composition for controlling the growth of butyric acid-producing bacteria, composition for controlling butyric acid production, composition for controlling the growth of Bifidobacterium bacteria, and use thereof
[0001] The present invention relates to a composition for controlling the growth of butyric acid-producing bacteria, a composition for controlling butyric acid production, a composition for controlling the growth of bacteria belonging to the genus Bifidobacterium, and uses thereof.
[0002] Butyric acid is a substance produced by intestinal bacteria that is expected to contribute particularly to health. Butyric acid is a type of short-chain fatty acid, and butyric acid produced in the intestine exhibits various effects, such as intestinal peristalsis, inflammation, and immunity. However, there is still little experience with butyric acid itself as food, and because butyric acid has a distinctive unpleasant odor, it is preferable to produce it endogenously in the body rather than directly ingesting it. As a means for producing butyric acid in the intestine, for example, an agent for promoting the increase of intestinal butyric acid concentration is known, which contains Lactobacillus acidophilus and / or Bifidobacterium longum as active ingredients (Patent Document 1).
[0003] Intestinal bacteria that produce butyric acid (butyric acid-producing bacteria) have been attracting attention as a type of intestinal bacteria that contributes significantly to health. Representative butyric acid-producing bacteria include bacteria belonging to the genera Faecalibacterium, Anaerostipes, Agathobacter, Anaerobutyricum, Roseburia, Coprococcus, Butyricimonas, and Eubacterium. Food ingredients that promote the growth of these butyric acid-producing bacteria are expected to have health benefits.
[0004] On the other hand, sugar alcohols are known to reach the large intestine without being digested or absorbed and to be utilized by intestinal bacteria. Therefore, sugar alcohols are low-calorie sweeteners and are also expected to function as prebiotics. Patent Document 2 describes an oral intestinal environment regulator that contains a colloid osmotic pressure regulator and / or a crystalloid osmotic pressure regulator, which eliminates harmful bacteria in the intestine and regulates the growth environment for beneficial bacteria. The crystalloid osmotic pressure regulator includes sugar alcohols such as sorbitol, xylitol, erythritol, mannitol, lactitol, and maltitol.
[0005] Furthermore, Patent Document 3 describes the use of a mixture of 6-O-α-D-glucopyranosyl-D-sorbitol (1,6-GPS) and 1-O-α-D-glucopyranosyl-D-mannitol (1,1-GPM) as a bifidobacterium-producing prebiotic and a butyrate-producing substrate, and demonstrates that fecal culture of this mixture increases the butyrate (butyric acid) concentration in the culture. Patent Document 4 describes a food, drink, pharmaceutical, or feed composition containing an indigestible saccharide selected from isomalt, isomaltulose, D-galactitol, D-xylitol, D-sorbitol, L-sorbose, maltitol, D-mannitol, lactitol, and galactooligosaccharides, and a butyric acid-producing bacterium, Anaerostipes hadrus (Eubacterium hadrum) YIT 12354 (NITE BP-01831) or Anaerostipes hadrus (Eubacterium hadrum) YIT 12355 (NITE BP-01832), and describes that xylitol is assimilated by the butyric acid-producing strains YIT 12354 and YIT 12355.
[0006] Japanese Patent Application Laid-Open No. 10-084909 International Publication No. WO2004 / 067037 Japanese Patent No. 4451879 Japanese Patent No. 6357222
[0007] Patent Document 3 describes that the concentration of butyric acid increases through fecal culture. However, since the increase in butyric acid concentration in the intestine can be attributed to various factors other than the production of butyric acid by butyric acid-producing bacteria, such as changes in absorption and metabolism by the host, Patent Document 3 does not disclose changes in the growth or function of butyric acid-producing bacteria. Furthermore, Patent Document 4 describes that xylitol is assimilated by the butyric acid-producing strains YIT 12354 and YIT 12355, but only describes assimilation and does not disclose the growth of butyric acid-producing bacteria.
[0008] In addition, there is a demand for prebiotic materials with excellent functionality and physical properties, and the search for sugar alcohol compounds with novel structures is also underway.
[0009] An object of the present invention is to provide a new means for controlling the growth of butyric acid-producing bacteria, or to provide a new means for controlling butyric acid production.
[0010] The present invention relates to the following: [1] A composition for controlling the growth of butyric acid-producing bacteria, comprising at least one selected from sugar alcohols and derivatives thereof. [2] The composition according to [1], wherein the butyric acid-producing bacteria are bacteria belonging to the genus Anaerostipes. [3] The composition according to [1], wherein the butyric acid-producing bacteria are bacteria belonging to the genus Eubacterium. [4] The composition according to any one of [1] to [3], wherein the growth is in the intestine. [5] The composition according to any one of [1] to [4], wherein the sugar alcohol is at least one selected from maltitol, inositol, palatinite, and xylitol. [6] The composition according to any one of [1] to [5], wherein the sugar alcohol is erythritol. [7] The composition according to any one of [1] to [4], wherein the sugar alcohol is at least one selected from inositol, palatinite, and erythritol. [8] The composition according to any one of [1] to [7], wherein the sugar alcohol derivative is at least one selected from the group consisting of maltitol derivatives, inositol derivatives, palatinite derivatives, xylitol derivatives, and erythritol derivatives. [9] The composition according to any one of [1] to [8], wherein the sugar alcohol derivative is a transglycosylated sugar alcohol.
[10] The composition according to any one of [1] to [9], wherein the transglycosylated sugar alcohol is a fructosylated sugar alcohol.
[11] The composition according to
[10] , wherein the fructosylated sugar alcohol is at least one selected from the group consisting of fructosylated maltitol, fructosylated inositol, fructosylated palatinite, fructosylated xylitol, and fructosylated erythritol.
[12] The composition according to any one of [1] to
[11] , wherein the growth control is growth promotion.
[13] The composition according to any one of [1] to
[12] , wherein the growth of bacteria belonging to the genus Bifidobacterium is controlled.
[14] The composition according to
[13] , wherein the control of the growth of bacteria belonging to the genus Bifidobacterium is promotion of the growth of bacteria belonging to the genus Bifidobacterium.
[15] A composition for controlling butyric acid production, comprising a sugar alcohol derivative.
[16] The composition according to
[15] , wherein the sugar alcohol derivative is at least one selected from the group consisting of maltitol derivatives, inositol derivatives, palatinite derivatives, xylitol derivatives, and erythritol derivatives.
[17] The composition according to
[15] , wherein the sugar alcohol derivative is a fructosylated sugar alcohol.
[18] The composition according to any one of
[15] to
[17] , wherein the butyric acid production is butyric acid production in the intestine.
[19] The composition according to any one of
[15] to
[18] , wherein the control of butyric acid production is promotion of butyric acid production.
[20] The composition according to any one of [1] to
[19] , wherein the composition is for one or more selected from the group consisting of improvement of intestinal peristalsis, suppression of inflammation, and enhancement of immunity.
[21] A composition for controlling the growth of bacteria belonging to the genus Bifidobacterium, comprising a sugar alcohol derivative.
[22] The composition according to
[21] , wherein the sugar alcohol derivative is at least one selected from the group consisting of maltitol derivatives, inositol derivatives, palatinite derivatives, xylitol derivatives, and erythritol derivatives.
[23] The composition according to
[21] , wherein the sugar alcohol derivative is a fructosylated sugar alcohol.
[24] The composition according to any one of [1] to
[23] , for use as a prebiotic or synbiotic.
[25] The composition according to any one of [1] to
[14] , wherein the growth of butyric acid-producing bacteria is in the intestine, and the control of the growth of the butyric acid-producing bacteria is mediated by an interaction between the butyric acid-producing bacteria and intestinal bacteria other than the butyric acid-producing bacteria.
[26] The composition according to
[25] , wherein the interaction comprises the butyric acid-producing bacteria assimilating a product produced by one or more intestinal bacteria other than the butyric acid-producing bacteria.
[27] A method for culturing butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium using a sugar alcohol derivative.
[28] The composition according to
[27] , wherein the sugar alcohol derivative is at least one selected from the group consisting of maltitol derivatives, inositol derivatives, palatinite derivatives, xylitol derivatives, and erythritol derivatives.
[29] The composition according to
[27] , wherein the sugar alcohol derivative is a fructosylated sugar alcohol.
[0011] Alternatively, the present invention relates to the following:
[30] A method or non-therapeutic method for controlling the growth of butyric acid-producing bacteria, comprising administering to a subject one or more selected from sugar alcohols and derivatives thereof. A sugar alcohol or a derivative thereof, or a composition comprising a sugar alcohol or a derivative thereof, for use in a method for controlling the growth of butyric acid-producing bacteria. Use of one or more selected from sugar alcohols and derivatives thereof, or use of a composition comprising one or more selected from sugar alcohols and derivatives thereof, for the manufacture of a composition for controlling the growth of butyric acid-producing bacteria. Use or non-therapeutic use of one or more selected from sugar alcohols and derivatives thereof, or use or non-therapeutic use of a composition comprising one or more selected from sugar alcohols and derivatives thereof, for controlling the growth of butyric acid-producing bacteria.
[31] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivatives thereof, use, or non-therapeutic use according to
[30] , wherein the butyric acid-producing bacteria is a bacterium belonging to the genus Anaerostipes.
[32] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to
[30] , wherein the butyric acid-producing bacteria is a bacterium belonging to the genus Eubacterium.
[33] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to any one of
[30] to
[32] , wherein the proliferation is proliferation in the intestine.
[34] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to any one of
[30] to
[33] , wherein the sugar alcohol is at least one selected from maltitol, inositol, palatinite, and xylitol.
[35] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to any one of
[30] to
[34] , wherein the sugar alcohol is erythritol.
[36] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to any one of
[30] to
[35] , wherein the sugar alcohol derivative is at least one selected from maltitol derivatives, inositol derivatives, palatinite derivatives, xylitol derivatives, and erythritol derivatives.
[37] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to any one of
[30] to
[36] , wherein the sugar alcohol derivative is a trans-sugar alcohol.
[38] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to any one of
[30] to
[37] , wherein the trans-sugar alcohol is a fructosylated sugar alcohol.
[39] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to
[38] , wherein the fructosylated sugar alcohol is at least one selected from fructosylated maltitol, fructosylated inositol, fructosylated palatinite, fructosylated xylitol, and fructosylated erythritol.
[40] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to any one of
[30] to
[39] , wherein the control of growth is promotion of growth.
[41] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to any one of
[30] to
[40] , for controlling the growth of bacteria belonging to the genus Bifidobacterium.
[42] The method, non-therapeutic method, sugar alcohol or a derivative thereof, composition comprising a sugar alcohol or a derivative thereof, use, or non-therapeutic use according to
[41] , wherein controlling the growth of bacteria belonging to the genus Bifidobacterium is promoting the growth of bacteria belonging to the genus Bifidobacterium.
[43] A method or non-therapeutic method for controlling butyric acid production, comprising administering a sugar alcohol derivative to a subject. A sugar alcohol derivative or a composition comprising a sugar alcohol derivative for use in a method for controlling butyric acid production. Use of a sugar alcohol derivative or use of a composition comprising a sugar alcohol derivative for manufacturing a composition for controlling butyric acid production. Use or non-therapeutic use of a sugar alcohol derivative, or use or non-therapeutic use of a composition comprising a sugar alcohol derivative for controlling butyric acid production.
[44] The method, non-therapeutic method, sugar alcohol derivative, composition comprising a sugar alcohol derivative, use, or non-therapeutic use according to
[43] , wherein the butyric acid production is butyric acid production in the intestine.
[45] The method, non-therapeutic method, sugar alcohol derivative, composition comprising a sugar alcohol derivative, use, or non-therapeutic use according to
[43] or
[44] , wherein the control of butyric acid production is promotion of butyric acid production.
[46] A method or non-therapeutic method for improving intestinal peristalsis, a method or non-therapeutic method for suppressing inflammation, and a method or non-therapeutic method for enhancing immunity, comprising administering one or more selected from sugar alcohols and their derivatives to a subject. A sugar alcohol or a derivative thereof, or a composition comprising a sugar alcohol or a derivative thereof, for use in a method for improving intestinal peristalsis, a method for suppressing inflammation, or a method for enhancing immunity. Use of one or more selected from sugar alcohols and derivatives thereof, or use of a composition comprising one or more selected from sugar alcohols and derivatives thereof, for the manufacture of a composition for one or more selected from improving intestinal peristalsis, suppressing inflammation, and enhancing immunity. Use or non-therapeutic use of one or more selected from sugar alcohols and derivatives thereof, or use or non-therapeutic use of a composition comprising one or more selected from sugar alcohols and derivatives thereof, for one or more selected from improving intestinal peristalsis, suppressing inflammation, and enhancing immunity.
[47] A method or non-therapeutic method for controlling the growth of bacteria belonging to the genus Bifidobacterium, comprising administering a sugar alcohol derivative to a subject. A sugar alcohol derivative, or a composition comprising a sugar alcohol derivative, for use in a method for controlling the growth of bacteria belonging to the genus Bifidobacterium or in a non-therapeutic method.Use of a sugar alcohol derivative, or use of a composition comprising a sugar alcohol, for the manufacture of a composition for controlling the growth of bacteria belonging to the genus Bifidobacterium. Use or non-therapeutic use of a sugar alcohol derivative, or use or non-therapeutic use of a composition comprising a sugar alcohol derivative, for controlling the growth of bacteria belonging to the genus Bifidobacterium.
[48] The method according to any one of
[30] to
[47] , or a non-therapeutic method, comprising administering one or more selected from sugar alcohols and their derivatives as a prebiotic or synbiotic. The sugar alcohol or derivative thereof according to any one of
[30] to
[47] , or a composition comprising a sugar alcohol or a derivative thereof, for use as a prebiotic or synbiotic. The use according to any one of
[30] to
[47] , or non-therapeutic use as a prebiotic or synbiotic.
[49] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to any one of
[30] to
[48] , wherein the growth of the butyric acid-producing bacteria is growth in the intestine, and the control of the growth of the butyric acid-producing bacteria is mediated by an interaction between the butyric acid-producing bacteria and intestinal bacteria other than butyric acid-producing bacteria.
[50] The method, non-therapeutic method, sugar alcohol or derivative thereof, composition comprising sugar alcohol or derivative thereof, use, or non-therapeutic use according to
[49] , wherein the interaction comprises the butyric acid-producing bacteria assimilating a product produced by one or more intestinal bacteria other than butyric acid-producing bacteria.
[0012] According to the present invention, the intestinal bacterial flora can be improved. According to one embodiment, the growth of butyric acid-producing bacteria can be controlled. According to one embodiment, butyric acid production can be controlled. According to one embodiment, the growth of bacteria belonging to the genus Bifidobacterium can be controlled.
[0013] The occupancy of Eubacterium when erythritol was added: Erythritol: p = 0.0807630479245294 (Wilcoxon signed-rank test). The occupancy of Anaerostipes bacteria when sugar alcohols were added: Maltitol: p = 0.025 (Wilcoxon signed-rank test), Inositol: p = 0.065 (Wilcoxon signed-rank test), Palatinit: p = 0.014 (Wilcoxon signed-rank test), Xylitol: p = 0.022 (Wilcoxon signed-rank test). The occupancy of Bifidobacterium bacteria when fructosylated maltitol was added: p = 3.07185E-05 (Wilcoxon signed-rank test). The occupancy of Anaerostipes bacteria when fructosylated maltitol was added. P = 3.05076E-06 (Wilcoxon signed rank test). Butyric acid concentration when fructosylated maltitol was added. Wilcoxon signed rank test: p = 0.004333)
[0014] The present invention will be described below. The features of the present invention described below can be combined in any combination.
[0015] <Composition> In one aspect, the present invention relates to a composition comprising one or more selected from sugar alcohols and their derivatives. In another aspect, the present invention relates to a composition comprising a sugar alcohol derivative. Regardless of which component is used in the composition of the present invention, the component is used at an intake level that is guaranteed to be safe or below the acceptable daily intake (ADI), in accordance with the food safety laws of each country.
[0016] [Active ingredient] (Sugar alcohol) In one embodiment, the composition of the present invention contains a sugar alcohol as an active ingredient. A sugar alcohol refers to a compound having a structure in which the carbonyl group of an aldose (a monosaccharide having an aldehyde group) or a ketose (a monosaccharide having a keto group) has been reduced (hydrogenated). The sugar alcohol may have, for example, a linear or cyclic carbon chain having 4 or more carbon atoms. An example of a sugar alcohol having a linear or cyclic carbon chain having 4 or more carbon atoms is erythritol (C 4 ) (C in bracketsn represents the number of carbon atoms in the sugar alcohol. The same applies below.), xylitol (C 5 ), inositol (C 6 ), sorbitol (C 6 ), mannitol (C 6 ), Volemitol (C 7 ), D-erythro-D-galacto-octitol (C 8 ), maltitol (C 12 ), Palatinit (C 12 ), lactitol (C 12 The configuration of the sugar alcohol is not limited unless otherwise specified.
[0017] In a preferred embodiment, the sugar alcohol is at least one selected from maltitol, inositol, palatinite, xylitol, and erythritol. In some embodiments, the sugar alcohol is at least one selected from maltitol, inositol, palatinite, and xylitol. In some embodiments, the sugar alcohol is erythritol.
[0018] The sugar alcohol may be a ready-made product, or may be one obtained by synthesis using a method known to those skilled in the art. Examples of ready-made sugar alcohols include those listed in the present Examples. Examples of methods for synthesizing sugar alcohols include, for example, palatinite, in which α-glucosyltransferase is allowed to act on sucrose to glucosyltransfer the glucose and fructose in sucrose from an α-1,2 bonded state to an α-1,6 bonded state to obtain palatinose, and the palatinose is then reduced (hydrogenated).
[0019] (Sugar Alcohol Derivative) In one embodiment, the composition of the present invention contains a sugar alcohol derivative as an active ingredient. In the present invention, a sugar alcohol derivative refers to a compound in which one or more OH groups at any position in a sugar alcohol have been modified, such as a trans-sugar alcohol, a sugar alcohol to which a polymeric carrier has been attached, or a sugar alcohol salt. The sugar alcohol derivative is preferably a trans-sugar alcohol. The sugar alcohol derivative may be, for example, a maltitol derivative, an inositol derivative, a palatinite derivative, a xylitol derivative, an erythritol derivative, a sorbitol derivative, a mannitol derivative, a volemitol derivative, a D-erythro-D-galacto-octitol derivative, or a lactitol derivative. In a preferred embodiment, the sugar alcohol derivative is at least one selected from maltitol derivatives, inositol derivatives, palatinite derivatives, xylitol derivatives, and erythritol derivatives. In another preferred embodiment, the sugar alcohol derivative is at least one selected from maltitol derivatives, inositol derivatives, palatinite derivatives, and xylitol derivatives; more preferably, the sugar alcohol derivative is a maltitol derivative.
[0020] Trans-Sugar Alcohol In the present invention, the term "trans-sugar alcohol" refers to a sugar alcohol to which a sugar is bound (dehydration condensation) via an OH group at any position of the sugar alcohol. The trans-sugar alcohol may be a sugar alcohol to which one or two or more sugar molecules are bound, preferably a sugar alcohol to which one, two, three, four, or five sugar molecules are bound, and more preferably a sugar alcohol to which one or two sugar molecules are bound. When two or more sugar molecules are bound to the sugar alcohol, the types of sugars may be one or more. Furthermore, the trans-sugar alcohol is preferably a fructosylated sugar alcohol (fructosylated sugar alcohol), a fucosylated sugar alcohol (fucosylated sugar alcohol), a glucosylated sugar alcohol (glucosylated sugar alcohol), or a galactosylated sugar alcohol (galactosylated sugar alcohol), and particularly preferably a fructosylated sugar alcohol. A fructosylated, fucosylated, glucosylated or galactosylated sugar alcohol refers to a sugar alcohol to which fructose, fucose, glucose or galactose is respectively bound.
[0021] In the case of a fructosylated sugar alcohol, for example, the transglycosylated sugar alcohol may be, for example, fructosylated maltitol, fructosylated inositol, fructosylated palatinite, fructosylated xylitol, fructosylated erythritol, fructosylated sorbitol, fructosylated mannitol, fructosylated volemitol, fructosylated D-erythro-D-galacto-octitol, fructosylated lactitol, etc.; in a preferred embodiment, it is at least one or more selected from fructosylated maltitol, fructosylated inositol, fructosylated palatinite, fructosylated xylitol, and fructosylated erythritol; in another preferred embodiment, it is at least one or more selected from fructosylated maltitol, fructosylated inositol, fructosylated palatinite, and fructosylated xylitol; and in a more preferred embodiment, it is fructosylated maltitol. Preferred specific examples of the trans-sugar alcohol, in the case of a fructosylated sugar alcohol, are one or more selected from the following (A) and (B): (A) a compound represented by the following formula (I), in which the 2-position of fructose is bound to the 1-position of maltitol; (B) a compound represented by the following formula (II), in which the 2-position of one molecule of fructose is bound to the 1-position of maltitol, and the 5-position of another molecule of fructose is bound to the 1-position of the fructose bound to maltitol.
[0022]
[0023]
[0024] The sugar alcohol to be used may be a ready-made product or one obtained by synthesis using a method known to those skilled in the art. Examples of methods for synthesizing sugar alcohols include a method comprising reacting β-fructofuranosidase obtained by a predetermined method with a sugar alcohol and a predetermined oligosaccharide (see, for example, Patent Documents 5 to 7).
[0025] Sugar alcohol with polymer carrier attached In the present invention, the sugar alcohol with polymer carrier attached refers to a sugar alcohol to which a polymer carrier is attached (dehydration condensation) via an OH group at any position of the sugar alcohol. The polymer carrier may be, for example, a hydrophilic polymer, and preferably a polymer containing one or more selected from polyethylene glycol, polyvinyl alcohol, povidone, hypromellose, copolyvidone, hydroxypropyl cellulose, polyvinyl alcohol-polyethylene glycol graft copolymer, hypromellose phthalate, and hypromellose acetate succinate. Sugar alcohol derivatives with such a structure are expected to have effects such as favorable delivery to target tissues and control of the duration of effect through metabolic regulation.
[0026] Sugar Alcohol Salt The sugar alcohol salt may be any salt as long as the effects of the present invention are not impaired, for example, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as magnesium salt and calcium salt; amine salts such as dimethylamine salt, triethylamine salt and ammonium salt; inorganic acid salts such as hydrochloride, perchlorate, sulfate and nitrate; or organic acid salts such as acetate and methanesulfonate. The sugar alcohol salt may be in the form of a solvate (e.g., hydrate). The number of solvent molecules in the solvate is not particularly limited.
[0027] [Uses] (Function) 1. Control of growth of butyric acid-producing bacteria In one embodiment, the composition of the present invention can be used to control the growth of butyric acid-producing bacteria. In a preferred embodiment, the composition of the present invention can be used to control the growth of butyric acid-producing bacteria in the intestine. In a more preferred embodiment, the composition of the present invention can be used to control the growth of butyric acid-producing bacteria in the human intestine. In the present invention, control of bacterial growth refers to controlling the number of bacteria. Control of growth is preferably promotion of growth.
[0028] Controlling proliferation in the intestine means controlling proliferation in the intestinal microbiota. In the present invention, the term "in the intestinal microbiota" is used to mean in the presence of a microbial community living in the intestine (the same applies hereinafter). The condition "in the intestinal microbiota" can be achieved, for example, by a method using feces or intestinal contents, a sample containing feces or intestinal contents, a sample prepared from feces or intestinal contents, etc. Alternatively, "in the intestinal microbiota" may be the intestine of a living organism (e.g., a mammal, preferably a human). The feces or intestinal contents may be obtained, for example, from a mammal, preferably from a human. The intestinal contents may include, for example, residue, intestinal fluid, feces, etc.
[0029] In the intestinal microflora, symbiotic relationships between bacteria also exist. Examples of symbiotic relationships include one bacterium utilizing the products of another bacterium, or another bacterium utilizing substances undesirable to that bacterium. Butyric acid-producing bacteria not only directly utilize one or more selected from sugar alcohols and their derivatives, but may also be influenced in some way by other bacteria that utilize one or more selected from sugar alcohols and their derivatives. For example, the butyric acid-producing bacterium Anaerostipes caccae is known to be able to utilize organic acids (lactic acid, acetic acid, etc.) and sugars produced by the intestinal bacterium Bifidobacterium infantis (Non-Patent Document 1). Furthermore, Anaerostipes caccae, Eubacterium aggregans, Eubacterium barkeri, Eubacterium hallii, Eubacterium limosum, Clostridium butyricum, Megasphaera elsdenii, and Coprococcus catus are known to convert lactic acid produced by bifidobacteria from carbohydrates into butyric acid (Non-Patent Document 2).
[0030] In one aspect, the growth of butyric acid-producing bacteria is in the intestine, and the regulation of the growth of butyric acid-producing bacteria is mediated by interactions between the butyric acid-producing bacteria and intestinal bacteria other than butyric acid-producing bacteria. This interaction may involve, for example, the butyric acid-producing bacteria assimilating products produced by one or more intestinal bacteria other than butyric acid-producing bacteria. The products may be proteins, polysaccharides, amino acids, sugars, organic acids, nucleic acids, fatty acids, etc. In one aspect, the intestinal bacteria other than butyric acid-producing bacteria are bacteria capable of assimilating sugar alcohols or derivatives thereof. Alternatively, the intestinal bacteria other than butyric acid-producing bacteria may be bacteria belonging to the genus Bifidobacterium (e.g., Bifidobacterium infantis).
[0031] Butyric acid-producing bacteria (sometimes referred to as butyric acid bacteria) refer to bacteria capable of producing butyric acid. Examples of butyric acid-producing bacteria include bacteria belonging to the genus Anaerostipes, Eubacterium, Faecalibacterium, Roseburia, Anaerobutyricum, Butyricimonas, Butyrivibrio, Coprococcus, Subdoligranulum, Anaerotruncus, Clostridium, Ruminococcus, Shuttleworthia, Lachnospira, Megashpaera, Butyricicoccus, and Gemmiger.
[0032] More specifically, the following bacteria are mentioned as butyric acid-producing bacteria: Anaerostipes caccae, Anaerostipes butyraticus, Anaerostipes handrus, Anaerostipes rhamnosivorans, SSC / 2, SS2 / 1, SS3 / 4, GM2 / 1, Eubacterium lomosum, Eubacterium rectale, Eubacterium aggregans, Eubacterium limosum, Eubacterium nodatum, Eubacterium oxidoreducens, Eubacterium ramulus, Eubacterium hallii, Eubacterium cylindroides, Faecalibacterium prausnitzii, Faecalibacterium longum, Faecalibacterium butyricigenerans, Faecalibacterium hattorii, Faecalibacterium duncaniae, Roseburia intestinalis, Roseburia faecis, Roseburia hominis, Roseburia inulinivorans, Roseburia ceccicola, Agathobacter rectalis Anaerobutyricum soehngenii, Butyricimonas synergistica, Butyricimonas virosa, Butyricimonas faecihominis, Butyricimonas paravirosa Butyrivibrio fibrisolvens, Butyrivibrio crossotus, Butyrivibrio proteoclasticus, Coprococcus catus, Coprococcus eutactus, Coprococcus comes, Eubacterium cylindroides, Subdoligranulum variabile, Anaerotruncus colihominis, Clostridiumacetobutylicum, Clostridium butyricum, Clostridium saccharobutylicum, Clostridium tyrobutyricum, Clostridium hathewayi, Clostridium indolis, Clostridium nexile, Clostridium symbiosum, Clostridium orbiscidens, Ruminococcus gnavus, Ruminococcus obeum, Shuttleworthia satelles, Lachonpira multipara, Lachnospira eligens, Lachonpira multiparis, Lachnospira pectinoschiza, Megasphaera elsdenii, Butyricicoccus pullicaecorum
[0033] In a preferred embodiment, the butyric acid-producing bacteria are one or more species selected from the group consisting of bacteria belonging to the genus Anaerostipes and bacteria belonging to the genus Eubacterium. The bacteria belonging to the genus Anaerostipes may be, for example, one or more species selected from Anaerostipes caccae, Anaerostipes butyraticus, Anaerostipes hadrus, and Anaerostipes rhamnosivorans. The bacteria belonging to the genus Eubacterium may be, for example, one or more species selected from Eubacterium lomosum, Eubacterium rectale, Eubacterium aggregans, Eubacterium limosum, Eubacterium nodatum, and Eubacterium oxidoreducens.
[0034] In the present invention, bacteria belonging to a certain genus refer to bacteria identified as belonging to that genus by phylogenetic analysis based on the 16S rRNA gene sequence. For criteria for determining whether a genera are the same or different based on the 16S rRNA gene sequence, those skilled in the art can refer to, for example, Stackebrandt E, Ebers J. Taxonomic parameters revisited: tarnished gold standards. Microbiol Today 2006;33:152-155.
[0035] Whether a certain component controls the growth of butyric acid-producing bacteria can be evaluated, for example, as follows: Butyric acid-producing bacteria are added to an appropriate medium at a certain cell count and cultured for a certain period of time under appropriate conditions as necessary. The component to be evaluated is then added and cultured for a certain period of time. The cell count of butyric acid-producing bacteria in the culture is then measured. The cell count can be measured according to a method known to those skilled in the art, such as counting the cell count under observation with an appropriate microscope or measuring the degree of turbidity (turbidity) of the culture system caused by the presence of bacteria using an appropriate photometric method. By comparing the cell counts before and after culture, it can be determined whether bacterial growth has been controlled. Alternatively, whether bacterial growth has been controlled can be determined by comparing the results with those obtained when an arbitrary control component is added instead of the component to be evaluated.
[0036] Whether a certain component inhibits the growth of butyric acid-producing bacteria can also be evaluated as follows. After culturing a medium containing feces provided by a healthy subject for a certain period of time as needed, the component to be evaluated is added thereto and cultured under appropriate conditions for a certain period of time. In this method, the growth of butyric acid-producing bacteria can also be evaluated by analyzing the occupancy rate of butyric acid-producing bacteria in the intestinal flora of the feces. The analysis method may include, for example, extracting DNA from the culture, amplifying the bacterial 16S rRNA gene by PCR, and analyzing it with a next-generation sequencer. In this method, for example, by comparing the results obtained using the component to be evaluated with the results obtained using an arbitrary control (e.g., ultrapure water), it can be determined whether bacterial growth has been inhibited.
[0037] When used to control the growth of butyric acid-producing bacteria, the active ingredient in the composition may be at least one selected from sugar alcohols and their derivatives. When used to control the growth of bacteria belonging to the genus Anaerostipes, the active ingredient in the composition may be, for example, at least one selected from sugar alcohols and their derivatives, preferably at least one selected from maltitol, inositol, palatinite, xylitol, erythritol, and their derivatives, more preferably at least one selected from maltitol, inositol, palatinite, xylitol, and their derivatives. When used to control the growth of bacteria belonging to the genus Eubacterium, the active ingredient in the composition may be, for example, at least one selected from sugar alcohols and their derivatives, preferably at least one selected from maltitol, inositol, palatinite, xylitol, erythritol, and their derivatives, more preferably at least one selected from erythritol and its derivatives.
[0038] 2. Control of Butyric Acid Production According to the present invention, butyric acid production can be controlled. That is, in one embodiment, the composition of the present invention can be used to control butyric acid production. In a preferred embodiment, the composition of the present invention can be used to control butyric acid production in the intestine. In a more preferred embodiment, the composition of the present invention can be used to control butyric acid production in the human intestine. Control of butyric acid production refers to controlling the amount of butyric acid produced. Control of butyric acid production preferably refers to promoting butyric acid production. Control of butyric acid production in the intestine refers to controlling butyric acid production in the intestinal bacterial flora.
[0039] Whether or not a certain component controls butyric acid production can be evaluated, for example, as follows: The component to be evaluated is added to a sample containing butyric acid-producing bacteria, and after a certain period of time has passed under an appropriate environment, the amount of acid produced in the sample is measured. The amount of acid produced may be measured according to a method known to those skilled in the art, such as a method using HPLC.
[0040] When used to control butyric acid production, the active ingredient in the composition may be a sugar alcohol derivative, preferably at least one selected from maltitol derivatives, inositol derivatives, palatinite derivatives, xylitol derivatives, and erythritol derivatives, more preferably at least one selected from maltitol derivatives, inositol derivatives, palatinite derivatives, and xylitol derivatives, and in one aspect is a maltitol derivative.
[0041] 3. Treatment of Diseases or Conditions It is known that butyric acid produced in the intestine has effects such as improving intestinal peristalsis, suppressing inflammation, and enhancing immunity (Non-Patent Document 3). Therefore, in one aspect, the composition of the present invention can be used to treat diseases or conditions caused by a decrease in intestinal butyric acid, specifically, for one or more effects selected from improving intestinal peristalsis, suppressing inflammation, and enhancing immunity. In the present invention, "treatment" includes prevention, amelioration, and inhibition of progression of diseases or symptoms.
[0042] When used to treat diseases or conditions caused by a decrease in butyric acid in the intestine, the active ingredient in the composition may be at least one or more selected from sugar alcohols and their derivatives, preferably at least one or more selected from maltitol, inositol, palatinite, xylitol, and erythritol and their derivatives, and more preferably at least one or more selected from maltitol, inositol, palatinite, and xylitol and their derivatives.
[0043] 4. Control of the growth of bacteria belonging to the genus Bifidobacterium The composition of the present invention can control the growth of bacteria belonging to the genus Bifidobacterium. That is, in one embodiment, the composition of the present invention can be used to control the growth of bacteria belonging to the genus Bifidobacterium. In a preferred embodiment, the control of the growth of bacteria belonging to the genus Bifidobacterium is the control of the growth of bacteria belonging to the genus Bifidobacterium in the intestines. In a more preferred embodiment, the control of the growth of bacteria belonging to the genus Bifidobacterium is the control of the growth of bacteria belonging to the genus Bifidobacterium in the human intestines. The control of growth is preferably the promotion of growth.
[0044] The bacterium belonging to the genus Bifidobacterium may be, for example, one or more species selected from Bifidobacterium adolescentis, Bifidobacterium longum (e.g., Bifidobacterium longum subsp. infantis, Bifidobacterium longum subsp. longum), Bifidobacterium infantis, Bifidobacterium pseudolongum, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium faecale, Bifidobacterium kashiwanohense, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium pseudocatenulatum, Bifidobacterium catenulatum, Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium gallicum, and Bifidobacterium lactis. Furthermore, examples of bacteria belonging to the genus Bifidobacterium found in human feces include Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium faecale, Bifidobacterium kashiwanohense, Bifidobacterium longum subsp. infantis, Bifidobacterium longum subsp. longum, Bifidobacterium pseudocatenulatum, Bifidobacterium dentium, Bifidobacterium gallicum, and Bifidobacterium pseudolongum subsp. globosum.
[0045] When used to control the growth of bacteria belonging to the genus Bifidobacterium, the active ingredient in the composition may be a sugar alcohol derivative, preferably at least one selected from maltitol derivatives, inositol derivatives, palatinite derivatives, xylitol derivatives, and erythritol derivatives, more preferably at least one selected from maltitol derivatives, inositol derivatives, palatinite derivatives, and xylitol derivatives, and in one aspect is a maltitol derivative.
[0046] As explained above, the composition of the present invention can control the growth of specific bacteria in the intestine. That is, the composition of the present invention can be used as a prebiotic or synbiotic. Prebiotics can be said to have a beneficial effect on the host by selectively altering the growth or activity of specific bacteria in the intestine. Furthermore, synbiotics refer to a combination of prebiotics and bacteria (probiotics) that have a beneficial effect on the host in the intestine.
[0047] (Subjects) Examples of subjects suitable for ingesting the composition of the present invention include: a healthy subject in whom it is desirable to control the proliferation of butyric acid-producing bacteria in the intestine; a healthy subject in whom it is desirable to control butyric acid production in the intestine; a healthy subject in whom it is desirable to prevent a disease or condition caused by a decrease in butyric acid in the intestine; a healthy subject in whom it is desirable to achieve one or more of the following: improvement of intestinal peristalsis, suppression of inflammation, and enhancement of immunity; a healthy subject in whom it is desirable to control the proliferation of bacteria belonging to the genus Bifidobacterium in the intestine. A healthy subject refers to a human who has not been diagnosed with any disease (pre-illness) or a companion animal as described below. In other words, when the composition of the present invention is used on these healthy subjects, the composition of the present invention is not provided for therapeutic purposes.
[0048] The composition of this embodiment can be used non-therapeutically. Non-therapeutic means not intended to treat a disease. In one embodiment, the composition of this embodiment can be used in the form of a food or the like (for example, as a food composition). In the above aspect, the composition is not a medicine, but is provided in the form of, for example, a supplementary food, health food, or supplement. Non-therapeutic use means maintenance of the current state, temporary improvement or relief, support, etc.
[0049] Examples of subjects suitable for ingesting the composition of the present invention include: subjects with a disease in which it is necessary or desirable to control the proliferation of butyrate-producing bacteria in the intestine; subjects with a disease in which it is necessary or desirable to control butyrate production in the intestine; subjects with a disease in which it is necessary or desirable to treat a disease or condition caused by a decrease in butyrate in the intestine; subjects with a disease in which it is necessary or desirable to treat one or more selected from improved intestinal peristalsis, suppression of inflammation, and enhanced immunity; subjects with a disease in which it is necessary or desirable to control the proliferation of bacteria belonging to the genus Bifidobacterium in the intestine.
[0050] The composition of the present invention can also be used for non-therapeutic purposes in subjects with diseases. In one embodiment, the composition of the present invention can be used in the form of a food or the like (e.g., as a food composition) as a composition for therapeutic support. Here, therapeutic support refers to non-therapeutic uses of disease or illness treatment. Examples of therapeutic support include use in subjects undergoing treatment for a disease or illness to enhance the therapeutic effect or provide nutritional support during treatment; use in subjects treated for a disease or illness to improve the prognosis, maintain a good prognosis, or provide nutritional support after treatment; and use in subjects scheduled to undergo treatment for a disease or illness to enhance the effect of subsequent treatment or provide nutritional support before treatment. In these embodiments, the composition is not provided as a pharmaceutical, but is provided in the form of, for example, a supplementary food, health food, liquid food, highly functional liquid food, supplement, etc. The composition of the present invention can also be used for therapeutic purposes in subjects with diseases. In one embodiment, the composition of the present invention can be used in the form of a pharmaceutical or the like (e.g., as a pharmaceutical composition) as a composition for therapeutic treatment.
[0051] When the composition of the present invention is used for non-therapeutic purposes, judgments as to whether it is desirable or necessary may include judgments as non-therapeutic actions, such as advice other than diagnosis, by medical professionals such as doctors, nurses, pharmacists, midwives, and clinical laboratory technicians, judgments by those involved in non-therapeutic actions, such as nutritionists (including registered dietitians and sports nutritionists), public health nurses, sports instructors, pharmaceutical manufacturers, pharmaceutical distributors, food manufacturers, and food distributors, judgments by the subject themselves or their family, etc. Furthermore, the above judgments include judgments based on the output results of questionnaires on lifestyle habits, eating habits, and subjective symptoms, and judgments based on subjective symptoms (concerns about obesity or lifestyle-related diseases, etc.).
[0052] When the composition of the present invention is used for therapeutic purposes, the necessity of the use can be judged as a therapeutic procedure by a medical professional such as a doctor, nurse, pharmacist, midwife, or clinical laboratory technician.
[0053] The subject may be a human or a non-human animal. Examples include mammals, birds, reptiles, amphibians, and fish. Preferably, the subject is a mammal, such as a human, mouse, rat, hamster, guinea pig, pig, or monkey, and more preferably a human. The non-human animal may be a commercial animal, a research animal, or a companion animal. The term "companion animal" refers to a domestic or domestic animal whose physical, emotional, behavioral, and social needs can be readily met through close daily association with one or more humans, or as a domestic companion. In one embodiment, species included within the definition of companion animal include dogs, canines, cats, felines, cows, horses, goats, sheep, pigs, primates (such as monkeys), rabbits, ferrets, rodents (such as guinea pigs, hamsters, mice, and rats), and other small mammals. In another embodiment, species included in the definition of companion animals include dogs, cats, horses, rabbits, ferrets, guinea pigs, and other small mammals, birds, small reptiles, fish, and livestock. Subjects suitable for ingesting the compositions of the present invention include those who have been found to have low intestinal butyrate-producing bacteria or Bifidobacterium bacteria or low butyrate levels in their intestines through any test or analysis, such as an intestinal microbiota test, a fecal substance test, or a fecal metabolome analysis; those who have been found to be at high risk for reduced intestinal peristalsis, inflammation, or reduced immunity; and those who have been recommended, based on the test or analysis results, by a doctor, nurse, pharmacist, nutritionist, or computer program, to take foods, beverages, or medicines that regulate the growth of butyrate-producing bacteria or Bifidobacterium bacteria or the production of butyrate in their intestines. The diagnosis of the disease or condition in a subject can also be determined by a doctor, nurse, pharmacist, or other professional, lifestyle or eating habits, the results of a symptom questionnaire, or the subject's own judgment based on subjective symptoms. The subject may be healthy (eg, not having a disease to be treated and not receiving therapeutic drugs, such as chemotherapeutic agents).
[0054] When the subject is human, suitable subjects for receiving the composition of the present invention include, for example, newborns (within 28 days of birth), infants (less than 1 year of age), toddlers (1 to 6 years of age), children (7 years of age or older, but younger than 15 years of age), adults (15 years of age or older), middle-aged and elderly people, people 60 years of age or older, elderly people (65 years of age or older (as defined by the World Health Organization (WHO))), people who are ill or recovering from an illness, pregnant women, and women who have just given birth.
[0055] [Form of Composition, etc.] The composition of the present invention can be a food composition or a pharmaceutical composition. Foods and pharmaceuticals include not only those for humans but also those for non-human animals, unless otherwise specified. Foods include general foods, functional foods, nutritional compositions, and therapeutic foods (those intended for therapeutic purposes, prepared based on a menu prepared by a nutritionist or other professional prescribed by a doctor), dietary therapy foods, ingredient-adjusted foods, nursing care foods, and therapeutic support foods, unless otherwise specified. Foods include not only solid foods but also liquid foods, such as beverages, energy drinks, liquid foods, and soups, unless otherwise specified. Functional foods refer to foods that can impart specific functionality to living organisms, and include a wide range of health foods, including foods with specified health uses (including conditional FOSHU [specified health foods]), foods with functional claims, foods with health claims, foods with nutrient function claims, foods for special dietary uses, foods with special dietary uses, dietary supplements, health supplements, supplements (e.g., tablets, coated tablets, sugar-coated tablets, capsules, liquids, etc.), and beauty foods (e.g., diet foods). In addition, in the present invention, the term "functional food" includes health foods to which a health claim based on the food standards of Codex Alimentarius (the Joint FAO / WHO Food Standards Commission) is applied.
[0056] [Content] The content (w / w%) of the active ingredient in the composition of the present invention may be, for example, 0.1% or more, 1% or more, 5% or more, 10% or more, or 20% or more, or may be 99% or less, 90% or less, 80% or less, or 70% or less. The above-mentioned content values may be appropriately combined to represent a content range.
[0057] [Dosage] The dosage of the active ingredient of the present invention can be appropriately determined taking into consideration various factors such as the age, body weight, symptoms, general condition, excretory function, and medical history of the subject to be ingested or administered. The dosage of the active ingredient of the present invention may be, for example, 5 mg or more, 10 mg or more, 50 mg or more, 100 mg or more, 300 mg or more, 500 mg or more, or 1000 mg or more per day, or may be 20 g or less, 10 g or less, or 5 g or less. The above-mentioned dosage values may be appropriately combined to express a dosage range.
[0058] [Route of Administration] The composition of the present invention may be administered parenterally, for example, via a tube (gastrostomy, enterostomy) or nasally, but is preferably administered orally.
[0059] [Administration Period] The administration period of the composition of the present invention may be, for example, 1 day or more, 3 days or more, 1 week or more, 2 weeks or more, 1 month or more, 3 months or more, 6 months or more, or 1 year or more.
[0060] [Other Ingredients and Additives] The composition of the present invention may contain other active ingredients or nutritional ingredients that are acceptable as foods or pharmaceuticals. Examples of such ingredients include amino acids (e.g., lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), carbohydrates (glucose, sucrose, fructose, maltose, trehalose, erythritol, maltitol, palatinose, xylitol, dextrin), electrolytes (e.g., sodium, potassium, calcium, magnesium), vitamins (e.g., vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, biotin, folic acid, pantothenic acid, and nicotinic acids), minerals (e.g., copper, zinc, iron, cobalt, manganese), antibiotics, dietary fiber, protein, lipids, etc.
[0061] The composition of the present invention may further contain additives acceptable for use as foods or pharmaceuticals, such as inert carriers (solid or liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, colorants, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavors, acidulants, and natural products. More specifically, examples of the additives include water, other aqueous solvents, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymers, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petrolatum, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, sucralose, stevia, aspartame, acesulfame potassium, citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, and vegetable juice.
[0062] [Dosage Form, Form] The food composition of the present invention may be prepared in any form, such as a solid, liquid, mixture, suspension, powder, granules, paste, jelly, gel, capsule, etc. Furthermore, the food composition of the present invention may be prepared in any form, such as dairy products, supplements (e.g., tablets, coated tablets, sugar-coated tablets, enteric-treated agents such as enteric coatings, capsules (enteric-coated soft capsules, enteric-coated hard capsules, large intestine delivery capsules), etc.), confectioneries, beverages, energy drinks, seasonings, processed foods, prepared dishes, soups, etc. More specifically, the composition of the present invention is a liquid food (semi-liquid food, concentrated liquid food, etc.), jelly, gel, powder, infant formula, infant formula liquid, powdered milk and liquid milk for pregnant and lactating women, fermented milk, bar, mousse, chocolate, biscuit, ice cream, fermented milk, lactic acid bacteria drink, dairy drink, dairy drink, soft drink, fruit juice drink, tablet, cheese, bread, biscuit, cracker, pizza crust, whiskey, bourbon, spirits, liqueur, wine, fruit wine, sake, Chinese sake, shochu, beer, non-alcoholic drinks with an alcohol content of 1% or less, etc. These products can be in the form of alcoholic beverages such as beer, happoshu (low-malt beer), other miscellaneous alcoholic beverages, and chuhai (Japanese shochu highballs); mineral water; processed products using eggs; processed products (including delicacies) made from seafood or meat (including liver and other offal); miso, soy sauce, furikake (rice seasoning), and other seasonings; soups such as miso soup; foods for the sick; nutritional foods; frozen foods; processed foods (e.g., tsukudani (foods boiled in soy sauce), boiled beans, steamed beans, pickles, salted kelp, etc.); and granules, powders, pastes, concentrated liquids, etc., to be mixed with beverages or foods. Granules and powders can be in cube or stick form (single-serving amounts packaged). Mineral water includes both sparkling and non-sparkling mineral water. As defined in the Ministerial Ordinance on the Compositional Standards of Milk and Dairy Products (hereinafter referred to as the "Milk Ordinance"), prepared powdered milk is made by processing raw milk, cow's milk, special cow's milk, or raw buffalo milk, or foods made from these ingredients, or by using these as the main ingredient, to which nutrients necessary for infants have been added and which have been made into a powder.As defined in the Ministerial Ordinance on Milk, etc., prepared liquid milk refers to raw milk, cow's milk, special milk, raw buffalo milk, or foods made from these ingredients, processed or used as the main ingredient, to which nutrients necessary for infants have been added and made into a liquid form. Fermented milk refers to fermented milk and lactic acid bacteria beverages as defined in the Ministerial Ordinance on Milk, etc., regarding the compositional standards, etc. of milk and dairy products (hereinafter referred to as the "Milk, etc., Ministerial Ordinance"). Fermented milk in the Milk, etc., Ministerial Ordinance is milk or milk containing an equivalent or higher non-fat milk solids that has been fermented with lactic acid bacteria or yeast to form a paste or liquid, or these products that have been frozen.
[0063] The pharmaceutical composition of the present invention can be made into any dosage form suitable for oral administration, such as solid preparations such as tablets, granules, powders, pills, and capsules; liquid preparations such as solutions, suspensions, and syrups; gels, aerosols, and live bacterial preparations. Solid preparations can be coated or sugar-coated, and can be enterically treated by enteric coating or the like. They can also be made into ointments, creams, topical liquid preparations, eye drops, nasal drops, suppositories, patches, and inhalants suitable for topical administration.
[0064] [Production Method] The composition of the present invention can be produced, for example, by mixing the active ingredient with other ingredients such as additives. Each ingredient may be added at any time as long as the properties of the active ingredient are not significantly impaired.
[0065] [Other] The composition of the present invention can be labeled with its intended use (use), or can be labeled with a recommendation that its intake be directed to a specific target. The specific target may be, for example, a target described in the "Target" section above. Labeling can be direct or indirect. Examples of direct labeling include inscription on tangible objects such as the product itself, packaging, containers, labels, and tags. Examples of indirect labeling include advertising and promotional activities via locations or means such as notifications via apps in AI diagnosis; websites; in-store; pamphlets; exhibitions; media seminars; books; newspapers; magazines; television; radio; video streaming sites; social media; influencer marketing; mail; email; audio; in-vehicle advertising on public transportation such as trains, buses, and bullet trains; street advertising such as street vision screens, billboards, and liquid advertising; social media; video sites; smartphones; smartwatches; tablet devices; PCs; and posters.
[0066] Examples of uses and functions that may be indicated for a food composition include the control of the growth of butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium or the control of butyric acid production; the ability to treat diseases or conditions that are improved by the control of the growth of butyric acid-producing bacteria or the control of butyric acid production (for example, improvement of intestinal peristalsis, suppression of inflammation, and enhancement of immunity); and the ability to be used as a probiotic or synbiotic.
[0067] In one embodiment, the recommendation to consume the composition of the present invention is displayed personally. Such a display can be made using a document (whether written or electronic) addressed to the subject, the subject's tablet device, smartphone, personal computer, the subject's social networking site, etc. Furthermore, such a display can be made together with the display of the results of any test or analysis, such as a blood test or blood metabolome test, for the subject.
[0068] In one aspect, there is provided a method for controlling the growth of butyrate-producing bacteria or bacteria belonging to the genus Bifidobacterium in the intestine of a subject, or a method for controlling butyrate production in the intestine of a subject, the method comprising the step of having the subject ingest a composition comprising a sugar alcohol or a derivative thereof, based on the number of butyrate-producing bacteria or bacteria belonging to the genus Bifidobacterium or the amount of butyrate in the intestine. In another aspect, there is provided a method for improving intestinal peristalsis, suppressing inflammation, or enhancing immunity in a subject, the method comprising the step of having the subject ingest a composition comprising a sugar alcohol or a derivative thereof, based on the number of butyrate-producing bacteria or the amount of butyrate in the intestine of the subject. In another aspect, there is provided a method for controlling butyrate production in the intestine of a subject, the method comprising the step of having the subject ingest a composition comprising a sugar alcohol derivative, based on the number of butyrate-producing bacteria or the amount of butyrate in the intestine. In yet another aspect, there is provided a method for suggesting to a subject the intake of a composition, a method for supporting the subject's diet, or a method for supporting the health of a subject, the method comprising the step of suggesting the intake of a composition containing a sugar alcohol or a derivative thereof based on the number of butyrate-producing bacteria or bacteria belonging to the genus Bifidobacterium or the amount of butyrate in the subject's intestine. The number of butyrate-producing bacteria or the amount of butyrate in the intestine can be obtained, for example, as a result of a differential intestinal flora (intestinal flora) test, a test for substances in feces, fecal metabolome analysis, etc. These methods may further include, for example, the following steps: collecting feces from the subject; measuring the occupancy rate of butyrate-producing bacteria or bacteria belonging to the genus Bifidobacterium in the intestinal flora from a sample containing the feces, or measuring the amount of butyrate in the intestine from a sample containing the feces; displaying the measurement results; determining, based on the measurement results, whether it is desirable or necessary to control the growth of butyrate-producing bacteria or bacteria belonging to the genus Bifidobacterium or the production of butyrate in the subject's intestine; displaying the determination result; and displaying a product that is a composition containing a sugar alcohol or a derivative thereof.
[0069] <Culturing Method> In one aspect, the present invention relates to a method for culturing butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium using a sugar alcohol derivative. According to the culturing method of the present invention, butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium can be efficiently grown.
[0070] A method for culturing butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium using a sugar alcohol derivative may, for example, include adding the sugar alcohol derivative to a culture system (typically a medium) containing butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium, or culturing butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium in a medium containing the sugar alcohol derivative. The sugar alcohol derivative may be arbitrarily selected as described above in the section (Sugar alcohol derivative). The concentration of the sugar alcohol derivative in the medium may be 0.01% or more, preferably 0.1%, more preferably 0.5%, and even more preferably 1% or more. The above-mentioned concentration may be satisfied at any time during the culture.
[0071] The butyric acid-producing bacteria used in the culture method of the present invention are not particularly limited, and may be selected from bacteria belonging to the genus Anaerostipes, bacteria belonging to the genus Eubacterium, bacteria belonging to the genus Faecalibacterium, bacteria belonging to the genus Roseburia, bacteria belonging to the genus Anaerobutyricum, bacteria belonging to the genus Butyricimonas, bacteria belonging to the genus Butyrivibrio, bacteria belonging to the genus Coprococcus, bacteria belonging to the genus Subdoligranulum, bacteria belonging to the genus Anaerotruncus, bacteria belonging to the genus Clostridium, bacteria belonging to the genus Ruminococcus, bacteria belonging to the genus Shuttleworthia, bacteria belonging to the genus Lachnospira, bacteria belonging to the genus Megashpaera, bacteria belonging to the genus Butyricicoccus, bacteria belonging to the genus Gemmiger, and the like.
[0072] Alternatively, the butyric acid-producing bacteria may be one or more species selected from the following: Anaerostipes caccae, Anaerostipes butyraticus, Anaerostipes handrus, Anaerostipes rhamnosivorans, SSC / 2, SS2 / 1, SS3 / 4, GM2 / 1, Eubacterium lomosum, Eubacterium rectale, Eubacterium aggregans, Eubacterium limosum, Eubacterium nodatum, Eubacterium oxidoreducens, Eubacterium ramulus, Eubacterium hallii, Eubacterium cylindroides, Faecalibacterium prausnitzii, Faecalibacterium longum, Faecalibacterium butyricigenerans, Faecalibacterium hattorii, Faecalibacterium duncaniae, Roseburia intestinalis, Roseburia faecis, Roseburia hominis, Roseburia inulinivorans, Roseburia ceccicola, Agathobacter rectalis Anaerobutyricum soehngenii, Butyricimonas synergistica, Butyricimonas virosa, Butyricimonas faecihominis, Butyricimonas paravirosa Butyrivibrio fibrisolvens, Butyrivibrio crossotus, Butyrivibrio proteoclasticus, Coprococcus catus, Coprococcus eutactus, Coprococcus comes, Eubacterium cylindroides, Subdoligranulum variabile, Anaerotruncus colihominis, Clostridiumacetobutylicum, Clostridium butyricum, Clostridium saccharobutylicum, Clostridium tyrobutyricum, Clostridium hathewayi, Clostridium indolis, Clostridium nexile, Clostridium symbiosum, Clostridium orbiscidens, Ruminococcus gnavus, Ruminococcus obeum, Shuttleworthia satelles, Lachonpira multipara, Lachnospira eligens, Lachonpira multiparis, Lachnospira pectinoschiza, Megasphaera elsdenii, Butyricicoccus pullicaecorum
[0073] In a preferred embodiment, the butyric acid-producing bacteria are one or more species selected from the group consisting of bacteria belonging to the genus Anaerostipes and bacteria belonging to the genus Eubacterium. The bacteria belonging to the genus Anaerostipes may be, for example, one or more species selected from Anaerostipes caccae, Anaerostipes butyraticus, Anaerostipes hadrus, and Anaerostipes rhamnosivorans. The bacteria belonging to the genus Eubacterium may be, for example, one or more species selected from Eubacterium lomosum, Eubacterium rectale, Eubacterium aggregans, Eubacterium limosum, Eubacterium nodatum, and Eubacterium oxidoreducens.
[0074] The bacteria belonging to the genus Bifidobacterium used in the culturing method of the present invention are not particularly limited, and may be, for example, one or more selected from the following. Bifidobacterium actinocoloniiforme, Bifidobacterium adolescentis, Bifidobacterium aerophilum, Bifidobacterium aesculapii, Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium aquikefiri, Bifidobacterium asteroides, Bifidobacterium avesanii Bifidobacterium biavatii, Bifidobacterium bifidum, Bifidobacterium bohemicum, Bifidobacterium bombi, Bifidobacterium boum, Bifidobacterium breve, Bifidobacterium callitrichos, Bifidobacterium catenulatum, Bifidobacterium choerinum, Bifidobacterium commune, Bifidobacterium coryneforme, Bifidobacterium crudilactis, Bifidobacterium denticolens, Bifidobacterium dentium, Bifidobacterium eulemuris, Bifidobacterium faecale, Bifidobacterium gallicum, Bifidobacterium gallinarum, Bifidobacterium hapali, Bifidobacterium indicum, Bifidobacterium inopinatum, Bifidobacterium kashiwanohense, Bifidobacterium lemurum, Bifidobacterium longum, Bifidobacterium magnum, Bifidobacterium merycicum, Bifidobacteriumminimum, Bifidobacterium mongoliense, Bifidobacterium moukalabense, Bifidobacterium myosotis, Bifidobacterium parvulorum, Bifidobacterium pseudocatenulatum, Bifidobacterium pseudolongum, Bifidobacterium psychraerophilum, Bifidobacterium pullorum, Bifidobacterium ramosum, Bifidobacterium reuteri, Bifidobacterium ruminale, Bifidobacterium ruminantium, Bifidobacterium saeculare, Bifidobacterium saguini, Bifidobacterium scardovii, Bifidobacterium simiae, Bifidobacterium stellenboschense, Bifidobacterium subtile, Bifidobacterium thermacidophilum, Bifidobacterium thermophilum, Bifidobacterium tissieri, Bifidobacterium tsurumiense
[0075] The culture conditions for butyric acid-producing bacteria in the culture method of the present invention are not particularly limited as long as they are suitable for culturing butyric acid-producing bacteria. For example, the culture conditions are 37°C, 5% CO 2 The culture period is not particularly limited as long as the butyric acid-producing bacteria can grow, and may be, for example, 1 hour or more, 6 hours or more, 12 hours or more, 1 day or more, 2 days or more, 3 days or more, or 1 week or more, or may be, for example, 3 weeks or less, or 2 weeks or less. The above-mentioned values of the culture period may be appropriately combined to represent a range of the culture period.
[0076] The medium used may be any medium suitable for culturing butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium, such as a medium suitable for evaluating sugar degradation ability, and preferably a semi-solid medium for GAM sugar degradation from which the agar has been removed by filtration.
[0077] In one embodiment, the culture method of the present invention comprises culturing butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium in intestinal flora. By culturing in intestinal flora, for example, butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium may not only directly utilize sugar alcohol derivatives, but also potentially utilize products produced by one or more intestinal bacteria other than butyric acid-producing bacteria and bacteria other than those belonging to the genus Bifidobacterium. Furthermore, for example, the butyric acid-producing bacterium Anaerostipes caccae is known to be able to utilize organic acids (such as lactic acid and acetic acid) and sugars produced by the intestinal bacterium Bifidobacterium infantis (Non-Patent Document 1).
[0078] The form of culturing in an intestinal microbiota is not particularly limited, as long as the culture is performed in the presence of a microbial community that inhabits the intestine. Culturing in an intestinal microbiota may, for example, involve culturing in feces or intestinal contents, a sample containing feces or intestinal contents, or a sample prepared from feces or intestinal contents. An example of culturing in an intestinal microbiota is culturing in a medium containing feces at a concentration of 0.001 to 10%, preferably 0.01 to 1%, per medium. The feces or intestinal contents may be obtained, for example, from a mammal, preferably from a human. The intestinal contents may include, for example, residue, intestinal fluid, feces, etc.
[0079] In one aspect, the culture method of the present invention comprises obtaining butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium. In another aspect, the present invention relates to a method for obtaining butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium cultured by the culture method of the present invention. Obtaining butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium may mean isolating butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium from a culture. Isolation of butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium from a culture may be performed by methods known to those skilled in the art, and the method may include, for example, the following procedures: spreading a culture solution containing the bacteria on an agar medium; allowing colonies to form on the agar medium; picking the colonies with a platinum loop and streaking them; again forming colonies and culturing them in liquid to isolate them.
[0080] In one aspect, the present invention relates to a method for producing butyric acid, which comprises culturing a butyric acid-producing bacterium by the culture method of the present invention. The method may also comprise purifying and separating butyric acid from the culture. The purification and separation of butyric acid can be carried out by methods known to those skilled in the art.
[0081] The present invention will be described below with reference to examples, but the present invention is not limited to these examples in any way.
[0082] Example 1: Effect of Erythritol on the Growth of Butyric Acid-Producing Bacteria (Method) Feces from six individuals were promptly refrigerated after excretion and stored frozen at -80°C until use. Each fecal sample was used for testing without mixing. A fecal dilution (six individuals, final concentration 0.1%) was prepared by suspending feces from healthy adults in "Nissui" semi-solid medium for GAM glycolysis (Nissui Pharmaceutical Co., Ltd.) from which the agar had been removed by filtration. Erythritol (Fujifilm Wako Pure Chemical Industries, Ltd., trade name: meso-erythritol (meso-1,2,3,4-tetrahydroquibutane, product number: 056-00242, lot: LEL6947) or ultrapure water (control) was added to a final concentration of 1%, and the samples were collected after 24 hours. The medium used for the test was left to stand overnight in an anaerobic glove box before use.
[0083] After incubation, DNA was extracted and purified from the diluted fecal samples using the Maxwell RSC PureFood GMO & Authentication Kit (Promega), and amplicon sequencing of the V3-V4 region was performed using MiSeq (Illumina). The resulting .fastq files were analyzed using QIIME2 (https: / / qiime2.org / ) to calculate the occupancy rate of Eubacterium bacteria.
[0084] (Results) The results of the bacterial flora analysis are shown in Figure 1. Of the six subjects, three did not carry Eubacterium, and the occupancy rate of Eubacterium did not change with or without erythritol addition. However, in the three subjects who carried Eubacterium, the occupancy rate of Eubacterium significantly increased with the addition of erythritol (Wilcoxon signed-rank test, p = 0.01198).
[0085] [Example 2] Effect of various sugar alcohols on the proliferation of butyric acid-producing bacteria (Method) Feces from six individuals were promptly aliquoted under refrigerated conditions after excretion and stored frozen at -80°C until use. Tests were conducted on each of these fecal samples without mixing. Feces from healthy adults were suspended in semi-solid medium for GAM glycolysis "Nissui" (Nissui Pharmaceutical Co., Ltd.) from which the agar had been removed by filtration (six individuals, final concentration 0.1%). Sugar alcohols (maltitol (Tokyo Chemical Industry Co., Ltd., trade name: Maltito, product number: M0797, lot: KQHOG-OC), inositol (Fujifilm Wako Pure Chemical Industries, Ltd., trade name: myo-inositol, product number: 092-00282, lot: PDK5015), Palatinit (Fujifilm Wako Pure Chemical Industries, Ltd., trade name: Palatinit, product number: 160-15422, lot: LEL6692), xylitol (Fujifilm Wako Pure Chemical Industries, Ltd., trade name: Xylitol, product number: 244-00542, lot: WTP2802) or ultrapure water (control) were added to the medium to a final concentration of 1%, and the medium was harvested after 24 hours. The medium used in the test was left to stand in an anaerobic glove box at least overnight before use.
[0086] After incubation, DNA was extracted and purified from the diluted fecal samples using the Maxwell RSC PureFood GMO & Authentication Kit (Promega), and amplicon sequencing of the V3-V4 region was performed using MiSeq (Illumina). The resulting .fastq files were analyzed using QIIME2 (https: / / qiime2.org / ) to calculate the occupancy rate of Anaerostipes bacteria.
[0087] (Results) The results of the bacterial flora analysis are shown in Figure 2. The occupancy rate of Anaerostipes bacteria significantly increased in samples to which any of the sugar alcohols was added (Wilcoxon signed-rank test).
[0088] The results of Examples 1 and 2 showed that sugar alcohols control the growth of butyric acid-producing bacteria.
[0089] Example 3: Effect of Fructosylated Maltitol on the Growth of Butyric Acid-Producing Bacteria (Method) Feces from 24 individuals were promptly refrigerated after excretion and stored frozen at -80°C until use. Each fecal sample was used for testing without mixing. A fecal dilution solution (24 individuals, final concentration 0.1%) was prepared by suspending feces from healthy adults in "Nissui" semi-solid medium for GAM saccharification (Nissui Pharmaceutical Co., Ltd.) from which the agar had been removed by filtration. Fructosylated maltitol or ultrapure water (control) was added to a final concentration of 1% and collected after 24 hours. The medium used in the test was left to stand in an anaerobic glove box for at least overnight before use. Fructosylated maltitol can be produced by the method described in Patent Document 5.
[0090] After incubation, DNA was extracted and purified from the diluted fecal samples using the Maxwell RSC PureFood GMO & Authentication Kit (Promega), and amplicon sequencing of the V3-V4 region was performed using MiSeq (Illumina). The resulting .fastq files were analyzed using QIIME2 (https: / / qiime2.org / ) to calculate the occupancy rates of Anaerostipes and Bifidobacterium bacteria. Furthermore, fecal organic acid analysis was performed after incubation.
[0091] Organic Acid Analysis: 450 μL of MilliQ, 12.5 μL of Karets 1 (ZnSO4·7H2O 53.5 g / 100 mL) solution, and 12.5 μL of Karets 2 (K4[Fe(CN)6]·3H2O 17.2 g / 100 mL) solution were added to 50 μL of fecal culture broth, and the mixture was centrifuged at 16,000 × g for 15 minutes at 4°C. The supernatant was then filtered through a 0.2 μm PVDF filter vial (1030-19022; Thomson) to prepare a sample for organic acid analysis. The concentrations of organic acids in the treated sample (citric acid, lactic acid, formic acid, acetic acid, propionic acid, butyric acid, malic acid, fumaric acid, isobutyric acid, isovaleric acid, and pyruvic acid) were analyzed by HPLC. The measurement conditions are shown in Table 1.
[0092]
[0093] (Results) The results of the bacterial flora analysis are shown in Figures 3 and 4. The occupancy rates of Bifidobacterium and Anaerostipes bacteria increased significantly. This suggests that fructosylated maltitol has the functions of both fructooligosaccharides and maltitol (see Example 2), and that the maltitol portion of the fructosylated maltitol structure was utilized by Anaerostipes bacteria, and the fructose portion was utilized by Bifidobacterium bacteria. In other words, fructosylated maltitol was considered to have the properties of FOS (fructooligosaccharides) (increased occupancy rate of Bifidobacterium) and the properties of maltitol (increased occupancy rate of Anaerostipes).
[0094] Therefore, in the intestines, fructosylated sugar alcohols can control (promote or inhibit growth of) bacteria whose growth can be controlled by sugar alcohols by using the sugar alcohol portion, and can promote the growth of Bifidobacterium bacteria by using the fructose portion.
[0095] For example, fructosylated inositol, fructosylated palatinite, and fructosylated xylitol can promote the growth of Bifidobacterium and Anaerostipes bacteria, while fructosylated erythritol can promote the growth of Bifidobacterium and Eubacterium bacteria (see Example 1).
[0096] Therefore, the results of Example 3 show that the sugar alcohol derivatives control the growth of butyric acid-producing bacteria and the growth of bacteria of the genus Bifidobacterium.
[0097] Next, the results of organic acid analysis are shown in Figure 5. In samples with added fructosylated maltitol, butyric acid significantly increased. There was a significant correlation between the occupancy rate of Anaerostipes bacteria and butyric acid concentration (Spearman's correlation coefficient = 0.57).
[0098] Anaerostipes bacteria are butyric acid-producing bacteria. It is believed that in the intestines of infants, Anaerostipes bacteria metabolize acetic acid produced by Bifidobacterium bacteria into butyric acid (Non-Patent Document 1). Therefore, fructosyl maltitol can be assimilated by both Bifidobacterium and Anaerostipes bacteria, potentially inducing strong butyric acid production. Similar effects can be expected with fructosylated inositol, fructosylated palatinite, and fructosylated xylitol. Therefore, the results of Example 3 demonstrate that butyric acid production is controlled by sugar alcohol derivatives.
[0099] Examples 1-3 demonstrated that sugar alcohols and their derivatives control the growth of butyric acid-producing bacteria. Furthermore, Example 3 demonstrated that butyric acid production increases with the growth of butyric acid-producing bacteria. Butyric acid is known to have effects such as improving intestinal peristalsis, suppressing inflammation, and enhancing immunity (Non-Patent Document 3). Therefore, sugar alcohols and their derivatives are believed to be useful for treating diseases or conditions caused by a decrease in intestinal butyric acid (e.g., decreased intestinal peristalsis, inflammation, and decreased immunity).
[0100] (References cited in the section on the preferred embodiment of the invention) Patent document 5: Japanese Patent Application Laid-Open No. 9-224665 Patent document 6: Japanese Patent Application Laid-Open No. 3-27285 Patent document 7: Japanese Patent Application Laid-Open No. 9-179492 Non-patent document 1: LW Chia et al. Cross-feeding between Bifidobacterium infantis and Anaerostipes caccae on lactose and human milk oligosaccharides. Benef Microbes. 2021 Feb 24;12(1):69-83. doi: 10.3920 / BM2020.0005. Non-patent document 2: Sato Nao et al., Verification of the in vivo butyrate-producing ability of human intestinal bacteria that convert lactic acid to butyrate, Japanese Journal of Bacteriology, 2006, Vol.61, p.138, III-E-13 Non-patent document 3: Hu Liu, Ji Wang, Ting He, Sage Becker, Guolong Zhang, Defa Li, Xi Ma. Butyrate: A Double-Edged Sword for Health? Adv Nutr. 2018 Jan 1;9(1):21-29. doi: 10.1093 / advances / nmx009.
[0101] The addition of the active ingredient of the present invention can provide functional foods in various forms.Furthermore, the present invention can provide a food composition and a method for producing a food that is useful for controlling the growth of butyric acid-producing bacteria, controlling butyric acid production, or controlling the growth of bacteria belonging to the genus Bifidobacterium, or that is useful for maintaining and improving the health of people who are not yet ill, or for supporting work efficiency.
Claims
1. A composition for controlling the growth of butyric acid-producing bacteria, comprising at least one selected from sugar alcohols and their derivatives.
2. The composition according to claim 1, wherein the butyric acid-producing bacterium is a bacterium belonging to the genus Anaerostipes.
3. The composition according to claim 1, wherein the butyric acid-producing bacterium is a bacterium belonging to the genus Eubacterium.
4. The composition according to any one of claims 1 to 3, wherein the proliferation is in the intestine.
5. A composition according to claim 1 or 2, wherein the sugar alcohol is at least one selected from maltitol, inositol, palatinite, and xylitol.
6. The composition according to claim 1 or 3, wherein the sugar alcohol is erythritol.
7. The composition according to claim 1, wherein the sugar alcohol derivative is at least one selected from the group consisting of maltitol derivatives, inositol derivatives, palatinite derivatives, xylitol derivatives, and erythritol derivatives.
8. The composition according to claim 7, wherein the sugar alcohol derivative is a trans-sugar alcohol.
9. The composition according to claim 8, wherein the transglycosylated sugar alcohol is a fructosylated sugar alcohol.
10. The composition according to claim 9, wherein the fructosylated sugar alcohol is at least one selected from the group consisting of fructosylated maltitol, fructosylated inositol, fructosylated palatinite, fructosylated xylitol, and fructosylated erythritol.
11. The composition of claim 1, wherein the control of proliferation is the promotion of proliferation.
12. The composition according to claim 1, which controls the growth of bacteria belonging to the genus Bifidobacterium.
13. The composition according to claim 12, wherein the control of the growth of bacteria belonging to the genus Bifidobacterium is the promotion of the growth of bacteria belonging to the genus Bifidobacterium.
14. The composition according to claim 1, wherein the proliferation of butyric acid-producing bacteria is in the intestine, and the control of the proliferation of butyric acid-producing bacteria is mediated by interaction between the butyric acid-producing bacteria and intestinal bacteria other than butyric acid-producing bacteria.
15. The composition of claim 14, wherein the interaction comprises the butyrate-producing bacteria utilizing a product by one or more species of intestinal bacteria other than the butyrate-producing bacteria.
16. A composition for controlling butyric acid production, comprising a sugar alcohol derivative.
17. The composition according to claim 16, wherein the butyric acid production is butyric acid production in the intestine.
18. The composition according to claim 16, wherein the regulation of butyric acid production is promotion of butyric acid production.
19. A composition according to any one of claims 1 to 3 and 7 to 18 for one or more of the following purposes: improving intestinal peristalsis, suppressing inflammation, and enhancing immunity.
20. A composition for controlling the growth of bacteria belonging to the genus Bifidobacterium, comprising a sugar alcohol derivative.
21. A composition according to any one of claims 1 to 3, 7 to 18 and 20 for use as a prebiotic or synbiotic.
22. A method for culturing butyric acid-producing bacteria or bacteria belonging to the genus Bifidobacterium using a sugar alcohol derivative.
Citation Information
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