Composition for promoting growth of bacteroides bacteria and use thereof
Xylose-based compositions enhance Bacteroides bacteria growth, addressing limitations in existing technologies by promoting intestinal proliferation and providing health benefits through interactions with other gut bacteria.
Patent Information
- Application Number
- JP2024073161
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-04-26
- Publication Date
- 2025-11-07
AI Technical Summary
Existing compositions for promoting the growth of Bacteroides bacteria are limited, and there is a need for effective methods to control and enhance the proliferation of these beneficial bacteria in the intestine for health benefits such as obesity prevention, dementia amelioration, and improved athletic performance.
A composition containing xylose is used to promote the growth of Bacteroides bacteria, either as a prebiotic or synbiotic, by interacting with other intestinal bacteria to enhance their proliferation and provide health benefits through direct assimilation of xylose and utilization of products produced by other intestinal bacteria.
Xylose effectively promotes the growth of Bacteroides bacteria, enhancing health benefits including inflammation reduction, obesity management, dementia improvement, glucose metabolism disorders treatment, and athletic performance enhancement.
Smart Images

Figure 2025168047000001_ABST
Abstract
Description
[Technical Field]
[0001] The present invention relates to a composition containing xylose for promoting the growth of bacteria belonging to the genus Bacteroides, and use of the composition. [Background technology]
[0002] In recent years, intestinal bacteria have been attracting attention due to their role in various diseases and symptoms. Among intestinal bacteria, bacteria belonging to the genus Bacteroides are the most common opportunistic bacteria.
[0003] Bacteroides bacteria are known to be associated with various health benefits, such as the prevention of obesity, fatty liver, and dementia. Recent research has shown that Bacteroides bacteria may also be associated with improved athletic performance (Non-Patent Document 1). Patent Document 1 also describes a composition containing Bacteroides uniformis or a processed product thereof, which is used to improve one or more of physical strength and fatigue resistance. Given these various expected health benefits, techniques for increasing Bacteroides bacteria are attracting attention.
[0004] For example, Patent Document 2 describes a composition for growing intestinal Bacteroides uniformis and a composition for improving athletic performance, each containing flaxseed lignan as an active ingredient. Patent Document 3 describes a composition for growing intestinal Bacteroides uniformis and a composition for improving athletic performance, each containing α-cyclodextrin as an active ingredient. [Prior art documents] [Patent documents]
[0005] [Patent Document 1] International Publication No. WO2019 / 069735 [Patent Document 2] International Publication No. WO2020 / 203196 [Patent Document 3] International Publication No. WO2020 / 203185 [Non-patent literature]
[0006] [Non-Patent Document 1] Morita et al., Bacteroides uniformis and its preferred substrate, α-cyclodextrin, enhance endurance exercise performance in mice and human males. Sci Adv. 2023 Jan 25;9(4):eadd2120. doi: 10.1126 / sciadv.add2120. Summary of the Invention [Problem to be solved by the invention]
[0007] An object of the present invention is to provide a new means for controlling the growth of bacteria belonging to the genus Bacteroides. [Means for solving the problem]
[0008] The present invention relates to the following: [1] A composition for controlling the growth of bacteria belonging to the genus Bacteroides, comprising xylose. [2] The composition described in [1], wherein the proliferation is proliferation in the intestine. [3] The composition according to [1] or [2] for use as a prebiotic or synbiotic. [4] The composition according to any one of [1] to [3], wherein the control of proliferation is promotion of proliferation. [5] The proliferation of bacteria belonging to the genus Bacteroides in the intestines. The composition according to any one of [1] to [4], wherein the control of the growth of bacteria belonging to the genus Bacteroides is mediated by an interaction between bacteria belonging to the genus Bacteroides and intestinal bacteria other than bacteria belonging to the genus Bacteroides. [6] The interaction The composition described in [5], wherein the bacterium belonging to the genus Bacteroides assimilates a product produced by one or more species of intestinal bacteria other than the bacterium belonging to the genus Bacteroides. [7] A composition comprising xylose for one or more of the following selected from the treatment of inflammation, the treatment of obesity, the treatment of dementia, the treatment of glucose metabolism disorders, the treatment of fatigue, and the improvement of athletic performance. [8] The composition described in [7], wherein one or more of the effects selected from the treatment of inflammation, obesity, dementia, glucose metabolism disorders, fatigue, and improved athletic performance are mediated by promoting the growth of bacteria belonging to the Bacteroides genus in the intestines. [9] A method for culturing bacteria belonging to the genus Bacteroides using xylose.
[10] The method according to [9], which comprises culturing bacteria belonging to the genus Bacteroides in the intestinal flora.
[0009] Alternatively, the present invention relates to the following:
[11] A method or non-therapeutic method for controlling the growth of bacteria belonging to the genus Bacteroides, comprising administering xylose to a subject. Xylose or a composition comprising xylose for use in a method for controlling the growth of bacteria belonging to the genus Bacteroides. Use of xylose or use of a composition comprising xylose for the manufacture of a composition for controlling the growth of bacteria belonging to the genus Bacteroides. Use or non-therapeutic use of xylose, or use or non-therapeutic use of a composition comprising xylose, for controlling the growth of bacteria belonging to the genus Bacteroides.
[12] A method for treating inflammation, a non-therapeutic method for treating inflammation, a method for treating obesity, a non-therapeutic method for treating obesity, a method for treating dementia, a non-therapeutic method for treating dementia, a method for treating glucose metabolism disorders, a non-therapeutic method for treating fatigue, a non-therapeutic method for treating fatigue, a method for improving athletic performance, or a non-therapeutic method for improving athletic performance, comprising administering xylose to a subject. Xylose or a composition comprising xylose for use in a method for treating inflammation, a method for treating obesity, a method for treating dementia, a method for treating glucose metabolism disorders, a method for treating fatigue, or a method for improving athletic performance. Use of xylose or use of a composition comprising xylose for the manufacture of a composition for one or more selected from the treatment of inflammation, the treatment of obesity, the treatment of dementia, the treatment of glucose metabolism disorders, the treatment of fatigue, and the improvement of athletic performance. Use or non-therapeutic use of xylose, or use or non-therapeutic use of a composition comprising xylose, for one or more selected from the treatment of inflammation, the treatment of obesity, the treatment of dementia, the treatment of glucose metabolism disorders, the treatment of fatigue, and the improvement of athletic performance.
[13] The method, non-therapeutic method, xylose, composition comprising xylose, use, or non-therapeutic use according to
[11] or
[12] , wherein the proliferation is proliferation in the intestine.
[14] A method or non-therapeutic method according to any one of
[11] to
[13] , comprising administering xylose as a prebiotic or synbiotic. Xylose according to any one of
[11] to
[13] , or a composition comprising xylose, for use as a prebiotic or synbiotic. Use or non-therapeutic use according to any one of
[11] to
[13] as a prebiotic or synbiotic.
[15] The method, non-therapeutic method, xylose, composition comprising xylose, use, or non-therapeutic use according to any one of
[11] to
[14] , wherein the control of proliferation is promotion of proliferation.
[16] The proliferation of bacteria belonging to the genus Bacteroides in the intestines The method, non-therapeutic method, xylose, composition comprising xylose, use, or non-therapeutic use according to any one of
[11] to
[15] , wherein the control of the growth of bacteria belonging to the genus Bacteroides is mediated by interaction between bacteria belonging to the genus Bacteroides and intestinal bacteria other than bacteria belonging to the genus Bacteroides.
[16] The interaction The method, non-therapeutic method, xylose, composition comprising xylose, use, or non-therapeutic use according to
[16] , comprising using bacteria belonging to the genus Bacteroides to utilize a product produced by one or more species of enterobacteria other than bacteria belonging to the genus Bacteroides.
[17] The method, non-therapeutic method, xylose, composition comprising xylose, use, or non-therapeutic use according to
[12] , wherein one or more of the following selected from treatment of inflammation, treatment of obesity, treatment of dementia, treatment of glucose metabolism disorders, treatment of fatigue, and improvement of athletic performance is mediated by promoting the growth of bacteria belonging to the genus Bacteroides in the intestine. [Effects of the Invention]
[0010] According to one embodiment of the present invention, the growth of bacteria belonging to the genus Bacteroides is controlled. [Brief explanation of the drawings]
[0011] [Figure 1] The occupancy rate of Bacteroides genus bacteria when xylose was added. p = 0.000447586139321597 (Wilcoxon signed-rank test) DETAILED DESCRIPTION OF THE INVENTION
[0012] The present invention will be described below. The features of the present invention described below can be combined in any combination.
[0013] <Composition> In one aspect, the present invention relates to a composition comprising xylose.
[0014] [Active ingredient] The composition of the present invention contains xylose as an active ingredient. Xylose may be in the D-, L-, or DL-form, and is preferably the D-form. Xylose may be a commercially available product (e.g., manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., trade name: D(+)-Xylose, product number: 244-00302, lot: WTN4592), or may be synthesized and isolated by a method known to those skilled in the art.
[0015] [Application] (function) In one embodiment, the composition of the present invention can be used to control the growth of bacteria belonging to the genus Bacteroides. In a preferred embodiment, the composition of the present invention can be used to control the growth of bacteria belonging to the genus Bacteroides in the intestines. In a more preferred embodiment, the composition of the present invention can be used to control the growth of bacteria belonging to the genus Bacteroides in the intestines of humans. Controlling bacterial growth refers to controlling the number of bacteria. Controlling growth is preferably promoting growth.
[0016] 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, for example, those obtained from a mammal, preferably those obtained from a human. The intestinal contents may include, for example, residue, intestinal fluid, feces, etc.
[0017] The composition of the present invention can control the growth of specific bacteria in the intestines. 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 intestines. Furthermore, synbiotics refers to a combination of prebiotics and bacteria (probiotics) that have a beneficial effect on the host in the intestines.
[0018] Symbiotic relationships between bacteria also exist within the intestinal microflora. Symbiotic relationships between bacteria include one bacterium utilizing the products of another bacterium, or another bacterium utilizing substances undesirable to that bacterium. Bacterium belonging to the genus Bacteroides not only directly utilizes xylose, but may also be influenced in some way by other xylose-using bacteria. In one embodiment, the growth of Bacteroides bacteria occurs within the intestine, and the control of the growth of Bacteroides bacteria is mediated by interactions between Bacteroides bacteria and intestinal bacteria other than Bacteroides bacteria. This interaction may involve, for example, the assimilation of products produced by one or more intestinal bacteria other than Bacteroides bacteria. The products may be proteins, polysaccharides, amino acids, sugars, organic acids, nucleic acids, fatty acids, etc. In one embodiment, the intestinal bacteria other than Bacteroides bacteria are bacteria capable of assimilating xylose.
[0019] Bacteria belonging to the genus Bacteroides include, for example, Bacteroides fragilis, Bacteroides uniformis, Bacteroides caccae, Bacteroides thetaiotaomicron, Bacteroides ovatus, Bacteroides xylanisolvens, Bacteroides stercorirosoris, Bacteroides eggerthii, Bacteroides finegoldii, Bacteroides acidifaciens, Bacteroides caecicola, Bacteroides caecigallinarum, Bacteroides caecimuris, Bacteroides cellulosilyticus, Bacteroides clarus, Bacteroides coprosuis, Bacteroides faecalis, Bacteroides faecichinchillae, Bacteroides faecis, Bacteroides fluxus, Bacteroides galacturonicus, Bacteroides gallinaceum, Bacteroides gallinarum, Bacteroides graminisolvens, Bacteroides helcogenes, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, Bacteroides luti, Bacteroides nordii, Bacteroides oleiciplenus, Bacteroides pectinophilus, Bacteroides polypragmatus, Bacteroides propionificaciens, Bacteroides pyogenes, Bacteroides reticulotermitis, Bacteroides rodentium, Bacteroides salyersiae, and Bacteroides stercoris.
[0020] In the present invention, bacteria belonging to the genus Bacteroides refer to bacteria identified as belonging to the genus Bacteroides by phylogenetic analysis 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, regarding criteria for determining whether a genera is the same or different based on the 16S rRNA gene sequence.
[0021] Whether or not a certain component controls the growth of bacteria belonging to the genus Bacteroides can be evaluated, for example, as follows: Bacteria belonging to the genus Bacteroides are added to an appropriate medium at a certain number of bacteria, and cultured for a certain period of time under appropriate conditions as necessary. A component to be evaluated is added to the medium, and cultured for a certain period of time. The number of bacteria belonging to the genus Bacteroides in the culture is then measured. The number of bacteria can be measured according to a method known to those skilled in the art, and such a method may include, for example, counting the number of bacteria under observation with an appropriate microscope, or measuring the degree of cloudiness (turbidity) of the culture system caused by the presence of bacteria using an appropriate photometric method. By comparing the number of bacteria before and after culture, it can be determined whether or not bacterial growth has been controlled. Alternatively, whether or not bacterial growth has been controlled may be determined by comparing with the results when an arbitrary control is added in place of the component to be evaluated.
[0022] Whether a certain component inhibits the growth of bacteria belonging to the genus Bacteroides 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 and cultured under appropriate conditions for a certain period of time. In this method, the growth of bacteria belonging to the genus Bacteroides can also be evaluated by analyzing the occupancy rate of bacteria belonging to the genus Bacteroides 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, whether bacterial growth has been inhibited can be determined, for example, by comparing the results obtained when the component to be evaluated is used with the results obtained when an arbitrary control (e.g., ultrapure water) is used.
[0023] Bacteria belonging to the genus Bacteroides are known to have effects such as amelioration of inflammation (Non-Patent Documents 2-3), obesity (Non-Patent Document 4), dementia (Non-Patent Document 5), glucose metabolism disorders (Non-Patent Document 6), fatigue (Patent Document 1), and athletic performance improvement (Non-Patent Document 1, Patent Documents 2-3). Therefore, in one embodiment, the composition of the present invention can be used for one or more selected from the treatment of inflammation, obesity, dementia, glucose metabolism disorders, fatigue, and athletic performance improvement. Examples of inflammation include intestinal inflammation, and examples of glucose metabolism disorders include type 2 diabetes. In the present invention, "treatment" includes prevention, amelioration, and inhibition of progression of a disease or symptom.
[0024] (subject) In one embodiment, the composition of the present invention is suitable for administration to a subject in need of or desiring to control the growth of Bacteroides bacteria in the intestine. In another embodiment, the composition of the present invention is suitable for administration to a subject in need of or desiring one or more of the following: improvement of inflammation, obesity, dementia, abnormal glucose metabolism, fatigue, and improved athletic performance. The subject is preferably a mammal, more preferably a human. Subjects in need of or desiring to control the growth of Bacteroides bacteria in the intestine include subjects who have been found to have low levels of Bacteroides bacteria in the intestine through any test or analysis, such as an intestinal microbiota test, a fecal substance test, or fecal metabolome analysis; subjects who have been found to be at high risk for inflammation, obesity, dementia, abnormal glucose metabolism, fatigue, or reduced athletic performance; and subjects who have been recommended, based on the test or analysis results, by a doctor, nurse, pharmacist, nutritionist, or computer program, to take a food, drink, or medicine that controls the growth of Bacteroides bacteria in the intestine. The judgment of the disease or condition in the subject includes judgment by a doctor, nurse, pharmacist, etc., lifestyle and eating habits, output results of a questionnaire on subjective symptoms, one's own judgment based on subjective symptoms, etc. The subject may be a healthy individual (e.g., a person who does not have a disease to be treated and is not receiving a drug for treatment, such as a chemotherapeutic agent).
[0025] Subjects suitable for taking the composition of the present invention include adults (15 years of age or older), middle-aged and elderly people, elderly people (65 years of age or older (as defined by the World Health Organization (WHO))), those currently recovering from illness, pregnant women, women who have just given birth, infants, and children. The active ingredients of the composition of the present invention are common ingredients used in food and are suitable for long-term intake.
[0026] [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, and nutritional compositions, as well as therapeutic foods (those intended for therapeutic purposes, such as those 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 diets, and soups, unless otherwise specified. Functional foods are foods that can impart specific functionality to the body, and include a wide range of health foods, including foods with specified health uses (including conditional FOSHUs [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). Furthermore, in the present invention, the term "functional food" encompasses health foods to which a health claim based on the food standards of Codex Alimentarius (the Joint FAO / WHO Food Standards Commission) is applied.
[0027] [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 express a content range.
[0028] [dose] The dosage of the active ingredient of the present invention can be appropriately determined taking into consideration various factors such as the age, weight, symptoms, and medical history of the subject to be ingested or administered. The dosage of the active ingredient of the present invention is not particularly limited as long as it is an amount that exhibits the desired effect, and 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 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.
[0029] [Administration route] The composition of the present invention may be administered parenterally, for example, enterally (gastrostomy, enterostomy), or intranasally, but is preferably administered orally.
[0030] [Administration period] The administration period of the composition of the present invention may be, for example, one day or more, three days or more, one week or more, two weeks or more, one month or more, three months or more, six months or more, or one year or more.
[0031] [Other ingredients, additives] The composition of the present invention may contain other active ingredients or nutritional components 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.
[0032] 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.
[0033] [Dosage form / shape] 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. The food composition of the present invention may also be prepared in any form, such as dairy products, supplements (e.g., tablets, coated tablets, sugar-coated tablets, enteric-coated agents, 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, liquid foods (semi-liquid foods, concentrated liquid foods, etc.), jellies, gels, powders, infant formula, infant liquid, powdered milk and liquid milk for pregnant and nursing women, fermented milk, bars, mousse, chocolate, biscuits, ice cream, fermented milk, lactic acid bacteria drinks, dairy drinks, dairy beverages, soft drinks, fruit juice drinks, tablets, cheese, bread, biscuits, crackers, pizza crust, whiskey, bourbon, spirits, liqueur, wine, fruit wine, sake, Chinese sake, shochu, beer, non-alcoholic beer with an alcohol content of 1% or less, These products can be in the form of alcoholic beverages such as happoshu (low-malt beer), other miscellaneous alcoholic beverages, and chuhai (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, thickened 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. Formulated powdered milk, as defined in the Ministerial Ordinance on the Compositional Standards of Milk and Dairy Products (hereinafter referred to as the "Milk, etc. Ministerial Ordinance"), refers to raw milk, cow's milk, special milk, or 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 powder. Formulated liquid milk, as defined in the Milk, etc. Ministerial Ordinance, refers to raw milk, cow's milk, special milk, or 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.Fermented milk is fermented milk and lactic acid bacteria beverages as defined in the "Ministerial Ordinance on the Compositional Standards 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 amount of 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.
[0034] 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. Furthermore, the composition can be made into ointments, creams, topical liquid preparations, eye drops, nasal drops, suppositories, patches, and inhalants suitable for topical administration.
[0035] [Manufacturing 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.
[0036] [others] The composition of the present invention may be labeled with its intended use (use) and may also be labeled with a recommendation for its intake to a specific target. The specific target may be, for example, a target described in the "Target" section above. Labeling may 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 AI diagnostic apps, websites, in-store displays, pamphlets, exhibitions, media seminars, books, newspapers, magazines, television, radio, mail, email, and audio; in-vehicle advertising on public transportation such as trains, buses, and bullet trains; street advertising such as street vision screens, billboards, and liquid advertisements; social media; video sites; smartphones; smartwatches; tablet devices; PCs; and posters.
[0037] Examples of uses and functions that may be indicated for a food composition include the ability to control the growth of bacteria belonging to the genus Bacteroides, the ability to treat diseases or conditions that are improved by controlling the growth of bacteria belonging to the genus Bacteroides (e.g., treatment of inflammation, treatment of obesity, treatment of dementia, treatment of glucose metabolism disorders, treatment of fatigue, and improvement of athletic performance), and the ability to be used as a probiotic or synbiotic.
[0038] In one embodiment, the recommendation to take 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.
[0039] In one aspect, a method for controlling the growth of bacteria belonging to the genus Bacteroides in the intestine of a subject is provided, comprising the step of administering to the subject a composition comprising xylose based on the number of bacteria belonging to the genus Bacteroides in the intestine. In another aspect, a method for improving inflammation, obesity, dementia, glucose metabolism disorders, fatigue, or athletic performance in a subject is provided, comprising the step of administering to the subject a composition comprising xylose based on the number of bacteria belonging to the genus Bacteroides in the intestine. In yet another aspect, a method for suggesting to a subject to ingest a composition, a method for supporting a subject's diet, or a method for supporting a subject's health is provided, comprising the step of suggesting to ingest a composition comprising xylose based on the number of bacteria belonging to the genus Bacteroides in the intestine. The number of bacteria belonging to the genus Bacteroides in the intestine can be obtained, for example, as a result of a differential intestinal flora (intestinal flora) test, a test of substances in feces, fecal metabolome analysis, etc. These methods may further comprise, for example, the steps of: A step of collecting feces from a subject; a step of measuring the occupancy rate of bacteria belonging to the genus Bacteroides in the intestinal flora from a sample containing feces; a step of displaying the measurement results; a step of determining, based on the measurement results, whether it is desirable or necessary to control bacteria belonging to the genus Bacteroides in the subject's intestines; a step of displaying the determination results; and a step of displaying a product that is a composition containing xylose.
[0040] <Culture method> In one aspect, the present invention relates to a method for culturing bacteria belonging to the genus Bacteroides using xylose. According to the culturing method of the present invention, bacteria belonging to the genus Bacteroides can be efficiently grown.
[0041] A method for culturing bacteria belonging to the genus Bacteroides using xylose may involve, for example, adding xylose to a culture system (typically a medium) containing bacteria belonging to the genus Bacteroides, or culturing bacteria belonging to the genus Bacteroides in a medium containing xylose. Xylose may be in the D-, L-, or DL-form, and is preferably the D-form. The concentration of xylose 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 point during the culture.
[0042] The species of bacteria belonging to the genus Bacteroides used in the culture method of the present invention is not particularly limited, and examples thereof include Bacteroides acidifaciens, Bacteroides caccae, Bacteroides caecicola, Bacteroides caecigallinarum, Bacteroides caecimuris, Bacteroides cellulosilyticus, Bacteroides clarus, Bacteroides coprosuis, Bacteroides eggerthii, Bacteroides faecalis, Bacteroides faecichinchillae, Bacteroides faecis, Bacteroides finegoldii, Bacteroides fluxus, Bacteroides fragilis, Bacteroides galacturonicus, Bacteroides gallinaceum, Bacteroides gallinarum, Bacteroides graminisolvens, Bacteroides helcogenes, Bacteroides intestinalis, Bacteroides koreensis, Bacteroides kribbi, and Bacteroides luti, Bacteroides nordii, Bacteroides oleiciplenus, Bacteroides ovatus, Bacteroides pectinophilus, Bacteroides polypragmatus, Bacteroides propionicifaciens, Bacteroides pyogenes, Bacteroides reticulotermitis, Bacteroides rodentium, Bacteroides salyersiae, Bacteroides stercorirosoris, Bacteroides It may be one or more selected from stercoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, and Bacteroides xylanisolvens.
[0043] The culture conditions for bacteria belonging to the genus Bacteroides in the culture method of the present invention are not particularly limited as long as they are suitable for culturing bacteria belonging to the genus Bacteroides, and may be, for example, an environment of 37°C and 5% CO2. The culture period is not particularly limited as long as it allows growth of bacteria belonging to the genus Bacteroides, 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 for the culture period may be appropriately combined to represent a range of the culture period.
[0044] The medium used may be any medium suitable for culturing bacteria belonging to the genus Bacteroides, such as a medium suitable for the growth of anaerobic bacteria, a medium suitable for evaluating sugar degradation ability, etc. A non-limiting example of such a medium is a semi-solid medium for GAM sugar degradation in which the agar has been removed by filtration.
[0045] In one embodiment, the culture method of the present invention comprises culturing bacteria belonging to the genus Bacteroides in an intestinal flora. By culturing in an intestinal flora, for example, bacteria belonging to the genus Bacteroides may not only directly utilize xylose, but also utilize products produced by one or more intestinal bacteria other than bacteria belonging to the genus Bacteroides. In one embodiment, the intestinal bacteria other than bacteria belonging to the genus Bacteroides are bacteria capable of assimilating xylose.
[0046] The form of culturing in the intestinal flora is not particularly limited, as long as the culture is performed in the presence of a microbial community that inhabits the intestine. Culturing in the intestinal flora 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 the intestinal flora 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 mammals, preferably from humans. The intestinal contents may include, for example, residue, intestinal fluid, feces, etc.
[0047] In one aspect, the culture method of the present invention comprises obtaining bacteria belonging to the genus Bacteroides. In another aspect, the present invention relates to a method for obtaining bacteria belonging to the genus Bacteroides cultured by the culture method of the present invention. Obtaining bacteria belonging to the genus Bacteroides may mean isolating bacteria belonging to the genus Bacteroides from the culture. Isolation of bacteria belonging to the genus Bacteroides from the culture may be carried out by methods known to those skilled in the art, for example, by a method using a selective isolation medium capable of isolating bacteria belonging to the genus Bacteroides (see, for example, Non-Patent Document 7). [Example]
[0048] The present invention will be further described below with reference to examples, but the present invention is not limited to these examples.
[0049] [method] The feces from the six individuals were promptly aliquoted under refrigerated conditions after voiding, and then frozen and stored at -80°C until use. Tests were conducted on each of these fecal samples without mixing them.
[0050] Feces from healthy adults were suspended in a semi-solid medium for GAM glycolysis "Nissui" (Nissui Pharmaceutical Co., Ltd.) from which the agar had been filtered, and diluted feces (6 individuals, final concentration 0.1%) was prepared. Xylose (Fujifilm Wako Pure Chemical Industries, Ltd., trade name: D(+)-Xylose, product number: 244-00302, lot: WTN4592) or ultrapure water (control) was added to a final concentration of 1%, and the medium was collected after 24 hours. The medium used in the test was left to stand at least overnight in an anaerobic glove box before use.
[0051] 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 Bacteroides species.
[0052] [result] The results of the bacterial flora analysis are shown in Figure 1. In the xylose-supplemented group, the occupancy rate of Bacteroides bacteria significantly increased.
[0053] These results indicate that xylose controls the growth of bacteria belonging to the genus Bacteroides. Bacteria belonging to the genus Bacteroides are also known to have effects such as amelioration of inflammation (Non-Patent Documents 2-3), obesity (Non-Patent Document 4), dementia (Non-Patent Document 5), glucose metabolism disorders (Non-Patent Document 6), fatigue (Patent Document 1), and athletic performance improvement (Non-Patent Document 1, Patent Documents 2-3). Therefore, xylose is thought to have effects such as amelioration of inflammation, obesity, dementia, glucose metabolism disorders, fatigue, and athletic performance improvement.
[0054] (References cited in the section on preferred embodiments of the invention) Non-Patent Document 2: Zaed Z R Hamady, Nigel Scott, Mark D. Farrar, Meenu Wadhwa, Paula Dilger, Terence R. Whitehead, Robin Thorpe, Keith T. Holland, J. Peter A Lodge, Simon R. Carding. Treatment of colitis with a commensal gut bacterium engineered to secrete human TGF-beta 1 under the control of dietary xylan. Inflamm Bowel Dis. 2011 Sep;17(9):1925-35. doi: 10.1002 / ibd.21565. Non-Patent Document 3: Zaed Z R Hamady, Nigel Scott, Mark D Farrar, J Peter A Lodge, Keith T Holland, Terence Whitehead, Simon R Carding. Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus. Gut. 2010 Apr;59(4):461-9. doi: 10.1136 / gut.2008.176131. Non-Patent Document 4: Ruth E Ley, Peter J Turnbaugh, Samuel Klein, Jeffrey I Gordon. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec 21;444(7122):1022-3. doi: 10.1038 / 4441022a. Non-patent document 5: Aura L Ferreiro, JooHee Choi, Jian Ryou, Erin P Newcomer, Regina Thompson, Rebecca M Bollinger, Carla Hall-Moore, I Malick Ndao, Laurie Sax, Tammie LS Benzinger, Susan L Stark, David M Holtzman, Anne M Fagan, Suzanne E Schindler, Carlos Cruchaga, Omar H Butt, John C Morris, Phillip I Tarr, Beau M Ances, Gautam Dantas, Gut microbiome composition may be an indicator of preclinical Alzheimer's disease. Sci Transl Med. 2023 Jun 14;15(700):eabo2984. doi: 10.1126 / scitranslmed.abo2984. Non-patent document 6: Hongying Ding, Yue Xu, Yinhong Cheng, Haoliang Zhou, Shiye Dong, Jian Wu, Jin Lv, Xiaosheng Hu, Oushan Tang. Gut microbiome profile of Chinese hypertension patients with and without type 2 diabetes mellitus. BMC Microbiol . 2023 Sep 9;23(1):254. doi: 10.1186 / s12866-023-02967-x. Non-patent document 7: F. Otani. Selective isolation medium for non-foaming anaerobic gram-negative bacilli. Japanese Journal of Bacteriology 25 (5-6), 1970 [Industrial Applicability]
[0055] By adding the active ingredient of the present invention, functional foods in various forms can be provided.Furthermore, the present invention can provide a food composition and a method for producing a food that is useful for controlling the growth of bacteria belonging to the genus Bacteroides, 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 bacteria belonging to the genus Bacteroides, comprising xylose.
2. The composition of claim 1 , wherein the proliferation is in the intestine.
3. 3. The composition according to claim 1 or 2 for use as a prebiotic or synbiotic.
4. The composition according to claim 1 or 2, wherein the control of proliferation is promotion of proliferation.
5. The proliferation of bacteria belonging to the genus Bacteroides in the intestines, 2. The composition according to claim 1, wherein the control of the growth of bacteria belonging to the genus Bacteroides is mediated by interaction between bacteria belonging to the genus Bacteroides and intestinal bacteria other than bacteria belonging to the genus Bacteroides.
6. The interaction is The composition according to claim 5, wherein the bacterium belonging to the genus Bacteroides utilizes a product produced by one or more species of intestinal bacteria other than the bacterium belonging to the genus Bacteroides.
7. A composition comprising xylose for one or more of the following selected from the treatment of inflammation, the treatment of obesity, the treatment of dementia, the treatment of glucose metabolism disorders, the treatment of fatigue, and the improvement of athletic performance.
8. The composition according to claim 7, wherein one or more of the effects selected from the group consisting of treatment of inflammation, treatment of obesity, treatment of dementia, treatment of glucose metabolism disorders, treatment of fatigue, and improvement of athletic performance are mediated by promoting the proliferation of bacteria belonging to the genus Bacteroides in the intestines.
9. A method for culturing bacteria belonging to the genus Bacteroides using xylose.
10. The method according to claim 9, comprising culturing bacteria belonging to the genus Bacteroides in the intestinal flora.
Citation Information
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