Composition for promoting proliferation of genus parabacteroides

Abstract

Provided is a composition for promoting the proliferation of the genus Parabacteroides, the composition containing any substance selected from sugar acid-containing oligosaccharides and salts thereof. The sugar acid-containing oligosaccharide is preferably maltobionic acid or lactobionic acid.

Description

Composition for promoting the growth of Parabacteroides bacteria

[0001] The present invention relates to a composition for promoting the growth of Parabacteroides bacteria, which comprises a sugar acid-containing oligosaccharide.

[0002] Parabacteroides is one of the most common bacteria present in the intestines of healthy adults and has recently attracted attention for its physiological functions beneficial to human health through acetate production and bile acid metabolism. Oral administration of Parabacteroides distasonis to ob / ob mice (a mouse model of type 2 diabetes and obesity) fed a high-fat diet has been reported to improve weight gain, glucose metabolism, and lipid metabolism. Parabacteroides also produces succinic acid, which is known to improve glucose metabolism and ameliorate obesity, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) (Non-Patent Documents 1 and 2). Furthermore, Parabacteroides is known to be reduced in the intestines of humans with psoriatic arthritis, inflammatory bowel disease, neonatal cholestasis, multiple sclerosis, non-alcoholic fatty liver disease, obesity, and metabolic syndrome (Non-Patent Document 3).

[0003] Several technologies have been investigated for promoting the growth of Parabacteroides bacteria. For example, Patent Document 1 describes a method for improving intestinal microbiota populations, the method comprising the step of administering a composition to a subject to increase a first intestinal microbiota population in the subject and simultaneously decrease a second intestinal microbiota population, the first intestinal microbiota population comprising short-chain fatty acid (SCFA)-producing bacteria, and the second intestinal microbiota population comprising endotoxin-producing bacteria. Parabacteroides is also described as one of the SCFA-producing bacteria. Patent Document 2 describes a method for reducing or reducing the risk of recurrence of inflammatory bowel disease (IBD), the method comprising administering an effective amount of a 2'-fucosyllactose compound to a subject in need thereof, the subject being a human IBD patient who has received or is receiving anti-inflammatory therapy. It is also described that the 2'-fucosyllactose compound is administered to the human patient in an amount sufficient to increase the abundance of intestinal microorganisms that produce short-chain fatty acids in the human patient, and that the intestinal microorganisms are Bifidobacteria, Bacteroides, and / or Parabacteroides. Patent Document 3 describes an agent for improving the intestinal flora during the intake of a high-fat diet, which contains epigallocatechin gallate (EGCG) and is characterized by: (1) reducing the Firmicutes / Bacteroidetes ratio and at least one selected from the group consisting of Mucispirillum, Ruminococcus, Anaerotruncus, and Oscillospira; and / or (2) increasing at least one genera selected from the group consisting of Adlercreutzia, Parabacteroides, Allobaculum, Clostridium, and Akkermansia.Patent Document 4 describes an active substance selected from the group consisting of riboflavin, vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, folic acid, β-carotene, vitamin B1, niacin, vitamin B5, vitamin B6, biotin, vitamin B12, ω-3 fatty acids, and combinations thereof, for use in improving the intestinal health of animals, including humans. The improvement also includes an increase in the diversity of the microflora in the intestinal tract, and Parabacteroides distasonis is described as one of the beneficial bacteria that increases the diversity. Patent Document 5 describes an agent for improving intestinal microorganisms that increases one or more bacteria of the genus (1) Bifidobacterium, (2) Erysipelothoricaceae, (3) Alphaproteobacteria, (4) Clostridiales, (5) Bradia, (6) Rickettsiales, and (7) Parabacteroides in the intestine, including lactic acid bacteria, butyric acid bacteria, and saccharifying bacteria. Patent Document 6 describes an agent for improving intestinal microflora that contains black soybean seed coat extract as an active ingredient. Patent Document 6 also describes an increase in the proportion of short-chain fatty acid-producing bacteria in intestinal bacteria as one of the effects of this agent, and describes bacteria of the genus Parabacteroides as one of the short-chain fatty acid-producing bacteria.

[0004] On the other hand, maltobionic acid and lactobionic acid are oligosaccharides having a structure in which gluconic acid is bound to glucose or galactose. Patent Document 7 describes a bifidobacterium growth promoter containing lactobionic acid as an active ingredient. Patent Document 8 describes an intestinal environment improver characterized by containing maltobionic acid, represented by the general formula 4-O-α-D-glucopyranosyl-D-gluconic acid, its salt, or maltobiono delta-lactone as an active ingredient. Patent Document 9 also describes an isoflavone absorption enhancer containing lactobionic acids. Maltobionic acid is not digested in vitro by saliva, gastric juice, or pancreatic juice, and is only digested to a small extent by small intestinal enzymes. However, it has been reported that, among 24 strains of intestinal bacteria, it was selectively utilized by Bifidobacterium dentium and B. adolescentis (Non-Patent Document 4). It has been reported that lactobionic acid has a particularly significant prebiotic effect in Lactobacillus fermentum (Non-Patent Document 5).

[0005] International Publication WO2013 / 182038 (Patent Publication No. 2015-520176) International Publication WO2018 / 187792 (Patent Publication No. 2020-513014) JP 2018-184363 A International Publication WO2020 / 043797 (Patent Publication No. 2021-535086) JP 2021-181409 A JP 2021-155375 A JP 7-277990 A JP 2009-143883 A International Publication WO2022 / 158595

[0006] Cell Reports 2019: 26(1): 222-235.Microbiome 2021: 9: Article number: 115FEMS Microbiol Lett. 2022;369(1):fnac072.J Appl Glycosci (1999). 2020; 67(1): 1-9.Appl Microbiol Biotechnol. 2019: 103(9): 3737-3751.

[0007] Because Parabacteroides is an obligate anaerobe, it is difficult to administer it as a probiotic. It would be desirable to have a method to increase Parabacteroides in the intestine.

[0008] The present invention provides the following: [1] A composition for promoting the growth of bacteria belonging to the genus Parabacteroides, comprising any one selected from sugar acid-containing oligosaccharides and salts thereof. [2] The composition according to [1], wherein the sugar acid is selected from aldonic acid, uronic acid, and aldaric acid. [3] The composition according to [1] or [2], wherein the sugar acid is aldonic acid. [4] The composition according to any one of [1] to [3], wherein the sugar acid is selected from gluconic acid, galactonic acid, xylonic acid, and arabinonic acid. [5] The composition according to any one of [1] to [4], wherein the sugar acid-containing oligosaccharide is a disaccharide. [6] The composition according to any one of [1] to [5], wherein the sugar acid-containing oligosaccharide is a disaccharide, and the monosaccharide constituting the disaccharide is selected from glucose, galactose, fructose, rhamnose, arabinose, mannose, and xylose. [7] The composition according to any one of [1] to [6], wherein the sugar acid-containing oligosaccharide is maltobionic acid or lactobionic acid. [8] The composition according to any one of 1 to 7, wherein the salt of the sugar acid-containing oligosaccharide is a calcium salt, a magnesium salt, a sodium salt, a potassium salt, a copper salt, an iron salt, or a zinc salt. [9] The composition according to any one of 1 to 8, for use as a prebiotic or a synbiotic.

[10] A composition for improving lipid metabolism, glucose metabolism, or obesity, comprising any one selected from sugar acid-containing oligosaccharides and salts thereof, and a composition for any one selected from the treatment of psoriatic arthritis, the treatment of inflammatory bowel disease, the treatment of neonatal cholestasis, and the treatment of multiple sclerosis.

[11] A composition for any one selected from sugar acid-containing oligosaccharides and salts thereof, for any one selected from the treatment of psoriatic arthritis, the treatment of inflammatory bowel disease, the treatment of neonatal cholestasis, and the treatment of multiple sclerosis, for supporting treatment.

[12] The composition according to 10 or 11, wherein the sugar acid is aldonic acid.

[13] The composition according to 10 or 11, wherein the improvement and treatment are mediated by promoting the growth of bacteria belonging to the genus Parabacteroides in the intestine.

[14] A composition for treating a disease or condition that is improved by promoting the growth of bacteria belonging to the genus Parabacteroides in the intestine, comprising any one selected from sugar acid-containing oligosaccharides and salts thereof.

[15] The composition according to 14, wherein the sugar acid is aldonic acid.

[16] A method for culturing a bacterium belonging to the genus Parabacteroides, characterized by using any one selected from sugar acid-containing oligosaccharides and salts thereof.

[17] The culture method according to 16, wherein the sugar acid is aldonic acid.

[0009]

[23] A food information providing device comprising: an information acquiring unit that acquires information on the intestinal flora of a subject; a derivation unit that derives information on foods to be provided to the subject based on the information on the intestinal flora; and a providing unit that provides the derived food information to the subject, wherein the information acquiring unit acquires information on the presence or amount of bacteria belonging to the genus Parabacteroides from the information on the intestinal flora, and the derivation unit derives information on foods that are compositions containing any one selected from sugar acid-containing oligosaccharides and salts thereof based on the information on the presence or amount of bacteria belonging to the genus Parabacteroides.

[24] The device according to 23, wherein the food information to be provided can be displayed on a terminal of the subject.

[25] The device according to 23 or 24, further comprising a display unit that displays the food information to be provided.

[26] A food information providing method comprising the steps of: acquiring information on the intestinal flora of a subject; deriving information on foods to be provided to the subject based on the information on the intestinal flora; and providing the derived food information to the subject, wherein in the information acquiring step, information on the presence or absence or amount of bacteria belonging to the genus Parabacteroides is acquired from the information on the intestinal flora, and in the food information deriving step, information on foods that are compositions containing any one selected from sugar acid-containing oligosaccharides and salts thereof is derive based on the information on the presence or absence or amount of bacteria belonging to the genus Parabacteroides.

[27] The method according to 26, further comprising the step of displaying the food information to be provided on a terminal of the subject.

[0010]

[101] A composition comprising any one selected from sugar acid-containing oligosaccharides and salts thereof, for use in a method for promoting the growth of bacteria belonging to the genus Parabacteroides. Use of any one selected from sugar acid-containing oligosaccharides and salts thereof in the manufacture of a composition for promoting the growth of bacteria belonging to the genus Parabacteroides. A method or non-therapeutic method for promoting the growth of bacteria belonging to the genus Parabacteroides, comprising the step of administering to a subject a composition comprising any one selected from sugar acid-containing oligosaccharides and salts thereof. A composition, use, or non-therapeutic use comprising any one selected from sugar acid-containing oligosaccharides and salts thereof for promoting the growth of bacteria belonging to the genus Parabacteroides.

[102] The composition, use in manufacture, method, or non-therapeutic method, or use or non-therapeutic use according to 101, wherein the sugar acid is selected from aldonic acid, uronic acid, and aldaric acid.

[103] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of

[101] or

[102] , wherein the sugar acid is aldonic acid.

[104] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of

[101] to

[103] , wherein the sugar acid is selected from gluconic acid, galactonic acid, xylonic acid, and arabinonic acid.

[105] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of

[101] to

[104] , wherein the sugar acid-containing oligosaccharide is a disaccharide.

[106] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of

[101] to

[105] , wherein the sugar acid-containing oligosaccharide is a disaccharide, and the monosaccharides constituting the disaccharide are selected from glucose, galactose, fructose, rhamnose, arabinose, mannose, and xylose.

[107] The composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use of any one of claims 101 to 106, wherein the sugar acid-containing oligosaccharide is maltobionic acid or lactobionic acid.

[108] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of items 101 to 107, wherein the salt of the sugar acid-containing oligosaccharide is a calcium salt, a magnesium salt, a sodium salt, a potassium salt, a copper salt, an iron salt, or a zinc salt.

[109] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of items 101 to 108, for use as a prebiotic or synbiotic.

[110] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of items 101 to 109, for use in a subject who is not obese, not insulin resistant, or not suffering from non-alcoholic fatty liver disease (NAFLD).

[111] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of items 101 to 110, which is targeted at a person who is not a patient with any of psoriatic arthritis, inflammatory bowel disease, neonatal cholestasis, and multiple sclerosis.

[112] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any of items 101 to 111, which is targeted at a person who is not a patient with metabolic syndrome, overweight, dysglycemia, or dyslipidemia.

[113] A composition comprising any one selected from sugar acid-containing oligosaccharides and salts thereof, for use in a method for improving lipid metabolism, improving glucose metabolism, and improving obesity, and for any one selected from the treatment of psoriatic arthritis, treatment of inflammatory bowel disease, treatment of neonatal cholestasis, and treatment of multiple sclerosis. Use of any one selected from sugar acid-containing oligosaccharides and salts thereof in the manufacture of a composition for improving lipid metabolism, glucose metabolism, and obesity, and for any one selected from the treatment of psoriatic arthritis, the treatment of inflammatory bowel disease, the treatment of neonatal cholestasis, and the treatment of multiple sclerosis. A method or non-therapeutic method for improving lipid metabolism, glucose metabolism, and obesity, and for any one selected from the treatment of psoriatic arthritis, the treatment of inflammatory bowel disease, the treatment of neonatal cholestasis, and the treatment of multiple sclerosis, comprising the step of administering to a subject a composition comprising any one selected from sugar acid-containing oligosaccharides and salts thereof.A composition, use, or non-therapeutic use comprising any one selected from sugar acid-containing oligosaccharides and salts thereof for improving lipid metabolism, glucose metabolism, and obesity, and for any one selected from the treatment of psoriatic arthritis, inflammatory bowel disease, neonatal cholestasis, and multiple sclerosis.

[114] The composition, use in production, method, or non-therapeutic method, or use or non-therapeutic use according to 113, wherein the improvement and treatment are mediated by promoting the growth of bacteria belonging to the genus Parabacteroides in the intestine.

[115] A composition comprising any one selected from sugar acid-containing oligosaccharides and salts thereof for use in a method for treating a disease or condition that is improved by promoting the growth of bacteria belonging to the genus Parabacteroides in the intestine. Use of any one selected from sugar acid-containing oligosaccharides and salts thereof in the manufacture of a composition for treating a disease or condition that is improved by promoting the growth of bacteria belonging to the genus Parabacteroides in the intestine. A method or non-therapeutic method for treating a disease or condition that is ameliorated by promoting the growth of bacteria belonging to the genus Parabacteroides in the intestine, comprising the step of administering to a subject a composition comprising any one selected from sugar acid-containing oligosaccharides and salts thereof.A composition, use, or non-therapeutic use comprising any one selected from sugar acid-containing oligosaccharides and salts thereof, for treating a disease or condition that is ameliorated by promoting the growth of bacteria belonging to the genus Parabacteroides in the intestine.

[0011] The use of sugar acid-containing oligosaccharides as prebiotics can increase the number of Parabacteroides bacteria in the intestine.

[0012] Number of Parabacteroides bacteria after cultivation Number of Parabacteroides bacteria after cultivation Turbidity of Parabacteroides bacteria 24 hours after cultivation Occupancy of Parabacteroides bacteria after fecal cultivation with the addition of various sugars or gluconic acid Change in OD=600nm when F. prausnitzzi is cultivated in the culture supernatant of P. distanios in a medium containing various sugars Change in OD=600nm when F. prausnitzzi is cultivated in the culture supernatant of P. merdae in a medium containing various sugars

[0013] The present invention relates to a composition for promoting the growth of bacteria of the genus Parabacteroides, which comprises, as an active ingredient, any one selected from the group consisting of sugar acid-containing oligosaccharides and salts thereof. Note that, in the present invention, the term "any one" means that the number and type of the active ingredient are optional.

[0014] [Active ingredient] The composition of the present embodiment contains, as an active ingredient, any one selected from sugar acid-containing oligosaccharides and salts thereof. Note that, in the following, among any one selected from sugar acid-containing oligosaccharides and salts thereof as the active ingredient, sugar acid-containing oligosaccharides may be used as an example for explanation, but the explanation also applies to salts of sugar acid-containing oligosaccharides unless otherwise specified.

[0015] Sugar acid-containing oligosaccharides refer to oligosaccharides containing sugar acids. Sugar acids are compounds in which one of the oxygen-containing functional groups (e.g., hydroxyl groups and aldehyde groups) of a monosaccharide is oxidized to a carboxyl group. Examples of sugar acids are aldonic acids, uronic acids, and aldaric acids. Aldonic acids are aldoses in which the terminal aldehyde group (formyl group) is oxidized, uronic acids are aldoses in which the terminal hydroxyl group is oxidized, and aldaric acids are aldoses in which both ends are oxidized. Sugar acids also include those in which oxygen-containing functional groups other than the terminal ones are oxidized to a carboxyl group.

[0016] In one embodiment, the sugar acid in the sugar acid-containing oligosaccharide that is the active ingredient of the composition is selected from aldonic acid, uronic acid, and aldaric acid, and in a preferred embodiment, it is aldonic acid. That is, in a particularly preferred embodiment, the active ingredient of the composition is an aldonic acid-containing oligosaccharide.

[0017] The aldonic acid moiety of the aldonic acid-containing oligosaccharide may be gluconic acid, galactonic acid, xylonic acid, arabinonic acid (sometimes called arabinonic acid), erythronic acid, threonic acid, ribonic acid, lyxonic acid, allonic acid, altronic acid, mannonic acid, gulonic acid, idonic acid, or talonic acid. In a preferred embodiment, the aldonic acid-containing oligosaccharide is one in which the aldonic acid is gluconic acid, galactonic acid, xylonic acid, or arabinonic acid. Gluconic acid, galactonic acid, xylonic acid, and arabinonic acid are preferred in terms of ease of production.

[0018] Aldonic acid-containing oligosaccharides are sometimes called oligosaccharide acids or sugar carboxylic acids. Aldonic acid is a type of derivative of aldose (polyhydroxyaldehyde).

[0019] The aldonic acid moiety of the aldonic acid-containing oligosaccharide may be gluconic acid, galactonic acid, xylonic acid, arabinonic acid (sometimes called arabinonic acid), erythronic acid, threonic acid, ribonic acid, lyxonic acid, allonic acid, altronic acid, mannonic acid, gulonic acid, idonic acid, or talonic acid. In a preferred embodiment, the aldonic acid-containing oligosaccharide is one in which the aldonic acid is gluconic acid, galactonic acid, xylonic acid, or arabinonic acid. Gluconic acid, galactonic acid, xylonic acid, and arabinonic acid are preferred in terms of ease of production.

[0020] The uronic acid moiety of the uronic acid-containing oligosaccharide may be glucuronic acid, galacturonic acid, iduronic acid, mannuronic acid, arabinonic acid, fructuronic acid, tagaturonic acid, or guluronic acid. In a preferred embodiment, the uronic acid moiety of the uronic acid-containing oligosaccharide is glucuronic acid, galacturonic acid, or iduronic acid, more preferably glucuronic acid.

[0021] The aldaric acid moiety of the aldaric acid-containing oligosaccharide may be glucaric acid, galactaric acid, or mannaric acid. In a preferred embodiment, the aldaric acid-containing oligosaccharide is one in which the aldaric acid is glucaric acid or galactaric acid.

[0022] In a preferred embodiment, the sugar acid in the sugar acid-containing oligosaccharide is selected from aldonic acid and uronic acid, more particularly gluconic acid and glucuronic acid.

[0023] The oligosaccharide portion of the sugar acid-containing oligosaccharide is not particularly limited as long as it can be assimilated by Parabacteroides bacteria, and may be glucose, galactose, fructose, rhamnose, arabinose, mannose, or xylose, or an oligosaccharide (such as a disaccharide or trisaccharide) composed of one or more of these.

[0024] The aldonic acid-containing oligosaccharide may be a disaccharide, a trisaccharide, or a saccharide of tetrasaccharide or more. Regarding the aldonic acid-containing oligosaccharide, a disaccharide refers to an oligosaccharide in which an aldonic acid is bound to a monosaccharide, and a trisaccharide refers to an oligosaccharide in which an aldonic acid is bound to a disaccharide. In a preferred embodiment, the aldonic acid-containing oligosaccharide is a disaccharide. When the aldonic acid-containing oligosaccharide is a disaccharide, the monosaccharide constituting the disaccharide is selected from glucose, galactose, fructose, rhamnose, arabinose, mannose, and xylose.

[0025] In the present invention, the term "salt of a sugar acid-containing oligosaccharide" refers to a salt acceptable for use as a food or pharmaceutical product. Examples of such salts include alkali metal salts (e.g., sodium salt, potassium salt), alkaline earth metal salts (e.g., calcium salt, magnesium salt), and other metal salts (copper salt, iron salt, zinc salt). The salt may be an anhydrous or solvated, and solvates include hydrates. Preferred examples of salts of aldonic acid oligosaccharides include calcium salt, magnesium salt, sodium salt, potassium salt, copper salt, iron salt, and zinc salt, with calcium salt being more preferred. While the following description may be given using a sugar acid-containing oligosaccharide as an example, among any of the active ingredients selected from sugar acid-containing oligosaccharides and their salts, the description generally also applies to salts of sugar acid-containing oligosaccharides, and those skilled in the art will understand this.

[0026] In a particularly preferred embodiment, the active ingredient of the composition is any one selected from maltobionic acid, isomaltobionic acid, maltotrionic acid, isomaltotrionic acid, maltotetraonic acid, maltohexanoic acid, cellobionic acid, lactobionic acid, nigerronic acid, kojibionic acid, panose oxide, and salts thereof, and is preferably any one selected from maltobionic acid, calcium maltobionate, and lactobionic acid. Maltobionic acid and lactobionic acid are hardly degraded by digestive enzymes such as saliva and the small intestine and pancreas, and reach the large intestine.

[0027] In one embodiment, the sugar acid-containing oligosaccharides and salts thereof as active ingredients are preferably capable of producing glucuronic acid in the intestine, which can promote the growth of butyric acid bacteria, such as Faecalibacterium, as described below.

[0028] Examples of sugar acid-containing oligosaccharides that can generate glucuronic acid in the intestine include gluconic acid-containing oligosaccharides and glucuronic acid-containing oligosaccharides. According to the studies of the present inventors, gluconic acid-containing sugars can generate gluconic acid in the intestine, and glucuronic acid can be generated from gluconic acid.

[0029] [Uses] (Functions, Actions, and Effects) The composition of the present embodiment can be used to promote the growth of bacteria belonging to the genus Parabacteroides (sometimes simply referred to as Parabacteroides bacteria). In one aspect, the composition can be used to promote the growth of Parabacteroides bacteria in the intestines.

[0030] The intestine refers to the digestive organ in humans and animals where bacteria normally reside and where ingested food is digested and absorbed. The intestine includes the small intestine and the large intestine, and preferably the large intestine.

[0031] Examples of Parabacteroides spp. include: Parabacteroides distasonis, Parabacteroides merdae, Parabacteroides johnsonii, Parabacteroides goldsteinii, Parabacteroides faecis, Parabacteroides acidifaciens, Parabacteroides chartae, Parabacteroides chinchillae, Parabacteroides chongii, Parabacteroides gordonii, Parabacteroides hominis.

[0032] In a preferred embodiment, the composition promotes the growth of any Parabacteroides species selected from P. distasonis and P. merdae.

[0033] In the present invention, the term "Parabacteroides" refers to bacteria identified as belonging to the genus Parabacteroides by molecular phylogenetic analysis based on the 16S rRNA gene. Criteria for determining genera based on molecular phylogenetic analysis based on the 16S rRNA gene are well known to those skilled in the art (Stackebrandt E, Ebers J. Taxonomic parameters revisited: tarnished gold standards. Microbiol Today 2006;33:152-155).

[0034] The ability of a certain component to promote the growth of Parabacteroides spp. can be assessed as follows: Culture broth of P. distasonis JCM5825T, P. merdae JCM9497T, P. johnsonii JCM 13406T, P. goldsteinii JCM13446T, P. faecis JCM18682T, or P. acidifaciens JCM34233T, stimulated in GAM medium, is added to an appropriate medium (e.g., GAM semi-solid medium for saccharification) containing the component of interest at an appropriate volume (e.g., 1%) and cultured under appropriate conditions (37°C, anaerobic conditions, 24 hours). The number, occupancy, or turbidity of Parabacteroides spp. in the culture is then measured. The results can then be compared with those of a culture cultured under identical conditions except for the addition of a control (e.g., sterile water) instead of the component of interest.

[0035] In particular, whether a substance promotes the growth of Parabacteroides in the intestine can be evaluated as follows: Feces containing Parabacteroides bacteria provided by a healthy individual is added to an appropriate medium and, if necessary, incubated for a certain period of time. After this, the component to be evaluated is added and incubated under appropriate conditions (e.g., 37°C, anaerobic conditions, 48 ​​hours, similar to intestinal conditions). The number or occupancy rate of Parabacteroides bacteria in the culture is then measured. The measurement results can then be compared with those of a culture incubated under identical conditions except for the addition of a control (e.g., sterilized water) instead of the component to be evaluated.

[0036] The number of Parabacteroides bacteria contained in the bacterial flora can be determined by known methods. One preferred method is to perform 16S metagenomic analysis (sequence analysis of 16S rRNA gene amplicons) on DNA extracted from the culture. When performing 16S metagenomic analysis, DNA extraction can be performed using a commercially available kit. The genomic region to be analyzed is not particularly limited as long as it allows identification of the bacteria, but the V3-V4 region of the 16S rRNA gene can be used. Primers, amplification conditions, amplicon purification, and other methods for bacterial analysis are also well known to those skilled in the art. Sequence analysis is preferably performed using a next-generation sequencer with higher performance. QIIME 2 is used to analyze the obtained data. TM For 16S metagenomic analysis, those skilled in the art can refer to information such as Sanschagrin S, Yergeau E. Next-generation sequencing of 16S ribosomal RNA gene amplicons. J Vis Exp. 2014;(90):51709. Published 2014 Aug 29. doi:10.3791 / 51709.

[0037] It has been reported that oral administration of Parabacteroides distasonis to ob / ob mice (a mouse model of type 2 diabetes and obesity) fed a high-fat diet improves weight gain, glucose metabolism, and lipid metabolism. Parabacteroides also produces succinic acid, which is known to improve glucose metabolism and ameliorate obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD) (Non-Patent Documents 1 and 2). Furthermore, Parabacteroides is known to decrease in the intestines of people with psoriatic arthritis, inflammatory bowel disease, neonatal cholestasis, multiple sclerosis, non-alcoholic fatty liver disease, obesity, and metabolic syndrome (Non-Patent Document 3). Therefore, the composition can be used to improve weight gain, glucose metabolism, and lipid metabolism. Inflammatory bowel diseases include ulcerative colitis and Crohn's disease.

[0038] When used for the treatment of inflammatory bowel disease, the composition may be configured to be free of any of the following: oligosaccharides (e.g., raffinose, stachyose, galactooligosaccharides, isomaltooligosaccharides, lactulose, xylooligosaccharides, agarooligosaccharides, mannooligosaccharides, or fructooligosaccharides), inulin, pectin, modified pectin, guar gum, hydrolyzed guar gum, psyllium seed gum, karaya gum, tragacanth gum, gum arabic, resistant starch, resistant dextrin, polydextrose, cellulose, hemicellulose, soybean polysaccharides, β-glucan, glucomannan, galactomannan, chondroitin sulfate, hyaluronic acid, levan, lignin, alginic acid and salts thereof, agarose, and chitosan.

[0039] When used for treating inflammatory bowel disease, the composition contains any one selected from sugar acid-containing oligosaccharides and salts thereof as an active ingredient, and may not contain any other oligosaccharides.

[0040] Furthermore, the composition can be used for the treatment of a variety of diseases or conditions that are improved by promoting the growth of Parabacteroides bacteria in the intestines.

[0041] In the present invention, the term "improvement" or "treatment" of a disease includes reducing the risk of onset, delaying onset, prevention, and cure. Treatment includes radical treatment (treatment to eliminate the cause) and symptomatic treatment (treatment to improve symptoms). Actions for improvement or treatment include medical procedures performed by physicians and nurses and midwives under the direction of physicians, as well as therapeutic procedures performed by persons other than physicians, such as pharmacists, midwives, nurses, clinical laboratory technicians, pharmaceutical manufacturers, and pharmaceutical distributors. The term "treatment" of a condition includes temporary improvement or alleviation of a condition, maintenance of a condition, halting progression, or delaying progression. Actions for improvement or treatment include non-therapeutic procedures performed by nutritionists (including registered dietitians and sports nutritionists), public health nurses, midwives, nurses, clinical laboratory technicians, sports instructors, pharmaceutical manufacturers, pharmaceutical distributors, food manufacturers, food distributors, and consumers themselves. Furthermore, maintenance and temporary improvement include recommendations for the intake of specific foods and nutritional guidance (including nutritional guidance necessary for the convalescence of injured or sick individuals, and nutritional guidance for maintaining and promoting health). Even if a subject is in a disease state, the composition is provided as a food (not a pharmaceutical) in accordance with the food labeling laws and regulations of each country at the time of implementation. For example, the composition can be used in the form of a food or other product as a therapeutic support composition. Here, therapeutic support refers to the treatment of a disease or illness but for non-therapeutic purposes. 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 or provide nutritional support after treatment, and use in subjects scheduled to undergo treatment for a disease or illness to enhance the therapeutic effect after treatment or provide nutritional support before treatment. In these embodiments, the composition is provided in the form of a non-pharmaceutical, such as a supplementary food, health food, or supplement. The composition is used, for example, as a therapeutic support composition for any treatment selected from the treatment of psoriatic arthritis, inflammatory bowel disease, neonatal cholestasis, and multiple sclerosis.

[0042] (Subjects) The composition of the present invention is suitable for administration to subjects for whom promoting the proliferation of Parabacteroides bacteria in the intestine is desirable or necessary; subjects for whom promoting intestinal acetic acid production is desirable or necessary; subjects with a disease or condition that can be prevented or improved by increasing intestinal acetic acid; subjects with a disease or condition caused by a decrease in intestinal acetic acid; subjects with or at risk of fatty liver; subjects with or at risk of obesity, dysglycemic metabolism, or dyslipidemia; subjects for whom improvement of any of weight gain, glucose metabolism, and lipid metabolism is desirable or necessary; and subjects with a disease or condition that can be improved by promoting the proliferation of Parabacteroides bacteria in the intestine. Determination of whether or not the composition is desirable or necessary includes judgment by a doctor, nurse, pharmacist, etc., judgment based on lifestyle habits, eating habits, and the output results of a subjective symptom questionnaire, etc., and judgment by the subject themselves based on subjective symptoms (e.g., concern about obesity or lifestyle-related diseases). Examples of subjects for whom promoting the growth of Parabacteroides bacteria is desirable or necessary include obese individuals, individuals with insulin resistance, individuals with non-alcoholic fatty liver disease (NAFLD), patients with psoriatic arthritis, inflammatory bowel disease, neonatal cholestasis, and multiple sclerosis, individuals with metabolic syndrome, and individuals with overweight, abnormal glucose metabolism, and abnormal lipid metabolism. In the present invention, the term "administer" is used to refer not only to administering a pharmaceutical product to a subject, but also to ingesting a non-pharmaceutical food product or the like. "Administer" can be interpreted as "intake" (or "ingestion"), and "administer" can be interpreted as "administered." The subject may be a human or a non-human animal. Non-human animals include mammals, birds, reptiles, amphibians, fish, and the like. Non-human animals may be commercial animals, research animals, or companion animals. The phrase "companion animal" refers to a domestic or domestically kept animal whose physical, emotional, behavioral, and social needs can be readily met as a domestic companion or in close daily association with one or more humans.In one embodiment, species included within the definition of companion animals include dogs, canines, cats, felines, cows, horses, goats, sheep, pigs, primates (such as monkeys), rabbits, ferrets, rodents (such as guinea pigs, hamsters, mice, rats), and other small mammals. In another embodiment, species included within the definition of companion animals are dogs, cats, horses, rabbits, ferrets, guinea pigs, and other small mammals, birds, small reptiles, fish, and livestock.

[0043] Subjects for whom it is desirable or necessary to promote the growth of Parabacteroides in the intestine include those for whom relatively low numbers of Parabacteroides bacteria are detected in at least one of their intestines and feces. Furthermore, subjects for whom it is desirable or necessary to promote the growth of Parabacteroides in the intestine include subjects who have been found to have relatively low numbers of Parabacteroides bacteria in the intestine through any test or analysis, such as an intestinal flora test, a test for substances in the feces, or a fecal metabolome analysis, subjects who have been found to be at high risk for obesity, glucose metabolism disorders, and lipid metabolism disorders, and subjects who have been recommended, based on the test or analysis results, by a doctor, nurse, pharmacist, nutritionist, or computer program, to consume foods, beverages, or medicines that promote the growth of Parabacteroides in the intestine.

[0044] The age of the subject is not particularly limited, and the subject may be, for example, a newborn (within 28 days of birth); an infant (less than 1 year of age); a toddler (1 to 6 years of age); a child (7 years of age or older, but less than 15 years of age); an adult (15 years of age or older); or a person 65 years of age or older.

[0045] [Composition] (Food 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 also therapeutic foods (those that serve the purpose of treatment; prepared based on a menu prepared by a nutritionist or other such person in accordance with a doctor's dietary prescription), therapeutic diets, ingredient-modified foods, nursing care foods, therapeutic support foods, health foods, dietary supplements, and functional health 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 a specific functionality to a living organism, and include all types of health foods, such as foods for specified health uses (including conditional FOSHUs [foods for specified health uses]), foods with functional claims, health functional foods including foods with nutrient function claims, foods for special dietary uses, dietary supplements, health supplements, 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, colon delivery capsules, etc.), beauty foods (e.g., diet foods), etc. Furthermore, in the present invention, "functional foods" includes health foods to which health claims based on the food standards of Codex Alimentarius (Joint FAO / WHO Food Codex) are applied. Note that when actually displaying a health claim on a food, the laws, treaties, regulations, etc. of the country (region) in which it is implemented at the time of implementation are followed.

[0046] (Route of Administration, etc.) The composition of the present invention may be administered orally, parenterally, for example, via a tube (gastrostomy, enterostomy), or nasally, but is preferably administered orally.

[0047] The composition can be administered to a subject repeatedly or continuously for a long period of time. The period is not particularly limited, but to ensure sufficient efficacy, it is preferable to administer the composition continuously for a relatively long period of time, for example, 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.

[0048] The compositions may be administered routinely, proactively, such as when at high risk, or when the need arises. The compositions may be administered with a meal, before a meal, after a meal, between meals, or at the onset of the disease or condition that the composition is intended to ameliorate.

[0049] (Dose, Content) The dose of the composition of the present invention may be any amount that achieves the desired effect. The dose can be appropriately determined taking into consideration various factors such as the age, weight, and symptoms of the subject.

[0050] The daily dose of the composition can be 0.1 g or more, preferably 0.3 g or more, more preferably 0.6 g or more, and even more preferably 1 g or more, of the active ingredient (total amount if multiple active ingredients are included). The upper limit of the active ingredient per day, regardless of the lower limit, can be 10 g or less, 9 g or less, 8 g or less, 7 g or less, 6 g or less, 5 g or less, or 4 g or less. When multiple active ingredients are included in the composition, the amount of active ingredient refers to the total amount of the active ingredients included.

[0051] Administration may be once a day or multiple times a day, for example, 2 to 10 divided doses. The amount of active ingredient per dose can be, for example, 0.01 g or more, preferably 0.3 g or more, more preferably 0.6 g or more, and even more preferably 1 g or more. The upper limit of the amount of active ingredient per dose, regardless of the lower limit, can be 10 g or less, 8 g or less, 6 g or less, 5 g or less, 4 g or less, 3 g or less, or 2 g or less.

[0052] The content of the active ingredient in the composition can be adjusted appropriately depending on the form of the composition. For example, the content of the active ingredient per solid content of the composition can be 0.5% or more, preferably 1% or more, more preferably 2% or more, and even more preferably 3% or more. The upper limit of the active ingredient per solid content, regardless of the lower limit, can be 20% or less, 18% or less, 16% or less, 13% or less, or 10% or less. In the present invention, % means % by mass unless otherwise specified.

[0053] When the composition is a liquid such as a beverage, the content of the active ingredient can be, for example, 0.1% or more, preferably 0.3% or more, more preferably 0.6% or more, even more preferably 1% or more, and even more preferably 2% or more. When the composition is a liquid, the upper limit of the content of the active ingredient, regardless of the lower limit, can be 15% or less, 10% or less, 8% or less, 6% or less, 4% or less, or 3% or less.

[0054] When the composition is in the form of a tablet or granular powder, the content of the active ingredient can be, for example, 10% or more, preferably 30% or more, more preferably 50% or more, and even more preferably 60% or more. When the composition is in the form of a tablet or granular powder, the upper limit of the content of the active ingredient can be 95% or less, 90% or less, or even 80% or less, regardless of the lower limit.

[0055] When the composition is a fermented milk such as yogurt, the content may be, for example, 2% or more, preferably 4% or more, and more preferably 10% or more. When the composition is a fermented milk such as yogurt, the upper limit of the content of the active ingredient may be 30% or less, 25% or less, or even 15% or less, regardless of the lower limit.

[0056] (Other Ingredients, 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 are selected from lipids (e.g., milk fat, vegetable oil, medium-chain fatty acid-containing oil), proteins (e.g., milk protein, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin (α-La), β-lactoglobulin (β-Lg), heat-denatured whey protein, and enzyme-treated whey protein), amino acids (e.g., lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), sugar-containing oligosaccharides, and salts thereof. carbohydrates other than those mentioned above (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, etc.

[0057] The composition of the present invention may contain a prebiotic other than a sugar acid-containing oligosaccharide and a salt thereof. Prebiotics can be defined as indigestible food ingredients that have a beneficial effect on the host and improve the host's health by selectively altering the growth and activity of specific bacteria in the large intestine. The composition may contain one or more prebiotics other than a sugar acid-containing oligosaccharide and a salt thereof. The composition of the present invention may also contain a probiotic. Examples of probiotics that can be used include Parabacteroides bacteria, lactic acid bacteria, and bifidobacteria. In particular, for subjects determined to have low levels of Parabacteroides in the intestinal tract, combination use with Parabacteroides bacteria is desirable.

[0058] The prebiotics other than the sugar acid-containing oligosaccharides and their salts are not particularly limited as long as they do not interfere with the effects of the active ingredients contained in the composition. Examples of prebiotics other than the sugar acid-containing oligosaccharides and their salts include galactooligosaccharides, fructooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, raffinose, lactulose, lactosucrose, soybean oligosaccharides, coffee oligosaccharides, dietary fiber, and gluconic acid.

[0059] The composition may further contain additives acceptable for use as food 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.

[0060] (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, or capsule. The food composition of the present invention may also be prepared in any form, such as a dairy product, supplement, confectionery, beverage, drink, seasoning, processed food, prepared dish, or soup. More specifically, the composition of the present invention may be in the form of a liquid diet, semi-liquid diet, jelly, gel, powder, infant formula, infant formula, liquid milk, powder or liquid milk for pregnant or nursing women, fermented milk, bar, mousse, chocolate, biscuit, ice cream, fermented milk, lactic acid bacteria drink, dairy drink, soft drink, tablet, cheese, bread, biscuit, cracker, pizza crust, food for the sick, nutritional food, frozen food, or processed food. It may also be in the form of a granule, powder, paste, or concentrated liquid for administration by mixing with beverages or foods. The granules and powder may be in the form of cubes or sticks (single-serving amounts packaged). In the present invention, modified powdered milk refers to raw milk, cow's milk, special cow's milk, or raw buffalo milk, or foods made from these as raw ingredients, processed or used as the main ingredient, to which nutrients necessary for infants have been added, and made into a powder, as defined in the Ministerial Ordinance on Milk, etc. In the present invention, modified liquid milk refers to raw milk, cow's milk, special cow's milk, or raw buffalo milk, or foods made from these as raw ingredients, processed or used as the main ingredient, to which nutrients necessary for infants have been added, and made into a liquid, as defined in the Ministerial Ordinance on Milk, etc.

[0061] Formulated powdered milk or formulated liquid milk (these are sometimes collectively referred to as formulae. In addition, formulae are sometimes explained using formulae as an example, but the explanation also applies to formulae liquid milk) can be for infants, follow-up (to supplement weaning food), low birth weight infants, children, adults, pregnant women, nursing women, the elderly, those with allergies, those with lactose intolerance, and those with inborn errors of metabolism. Preferred examples of formulae are those for infants, follow-up, low birth weight infants, and children.

[0062] 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; and aerosols.

[0063] (Other) In the production of the composition of the present invention, the stage of blending the active ingredient can be selected as appropriate. The stage of blending is not particularly limited as long as it does not significantly impair the properties of the active ingredient. For example, the active ingredient can be blended by mixing it with raw materials. Alternatively, the active ingredient can be added at the final stage of production to produce a composition containing the active ingredient.

[0064] The composition of the present invention can be labeled with its intended use (application), and in one embodiment, the function of the composition or active ingredient or the usage method based on that function is labeled. Examples of the usage method based on the function are as described above for the functions, actions, and effects. In addition, the composition of the present invention can be labeled with its ability to be used as a prebiotic or as a synbiotic (a combination of probiotics and prebiotics).

[0065] In one embodiment, the composition of the present invention is labeled to recommend administration to a specific subject. Examples of subjects to be labeled are as described above for subjects.

[0066] Representation can be explicit or implicit. Examples of explicit representations are direct descriptions on tangible objects such as the product itself, packaging, containers, labels, tags, etc., while examples of implicit representations (which can also be called implied) include advertising and promotional activities by place or means such as websites, stores, pamphlets, exhibitions, seminars such as media seminars, books, newspapers, magazines, television, radio, mail, email, and audio.

[0067] In one embodiment, the recommendation to consume the composition is displayed personally. Such a display can be provided via 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 provided together with the results of any test or analysis, such as a gut flora test, a fecal substance test, or a fecal metabolome analysis, for the subject.

[0068] [Device, provision method, etc.] In this embodiment, a food provision device is provided, comprising: an information acquisition unit that acquires information on the intestinal flora of a subject; a derivation unit that derives information on food to be provided to the subject based on the information on the intestinal flora; and a provision unit that provides the derived food information to the subject.

[0069] In a preferred embodiment, the information acquisition unit of the device acquires information on the presence or amount of Parabacteroides bacteria from information on the intestinal bacterial flora, and the derivation unit derives information on a food that is a composition containing one selected from sugar acid-containing oligosaccharides and salts thereof based on the information on the presence or amount of Parabacteroides bacteria.

[0070] In one embodiment, along with obtaining information on the subject's intestinal microbiota, any of the following information about the subject may be obtained: attribute information including any selected from the group consisting of the subject's sex and age; test result information on the subject's physical and health condition including any selected from the group consisting of the subject's height, weight, body mass index (BMI), obesity level, body fat, abdominal circumference, blood pressure, lipids, liver and pancreas function, metabolic system, blood, urine, kidney function, and large intestine; survey results information on the subject's preferences and lifestyle including any selected from the group consisting of the subject's eating habits (preferences), drinking habits, smoking habits, smoking history, exercise habits, and sleep time; and the subject's subjective symptoms, stress, illnesses currently being treated or monitored, medications and health foods being taken, medical history, and experience of pregnancy and childbirth; and other information about the subject's work history and general lifestyle.

[0071] The information may be obtained based on responses obtained from the subject to predetermined questions (eg, responses to a questionnaire).

[0072] In one aspect, the food information providing device can display the provided food information on a target terminal. In another aspect, the device further includes a display unit that displays the provided food information. The display unit can be a target terminal, such as a tablet terminal, a smartphone, or a personal computer.

[0073] In one aspect, the food information providing device may include an analysis unit that analyzes the bacterial flora of a sample obtained from the subject, and may also include an order receiving unit that receives an order for food from the subject based on the provided food information.

[0074] This embodiment also provides a food information providing method, which includes the following steps: acquiring information on the intestinal microbiota of a subject; deriving information on foods to be provided to the subject based on the information on the intestinal microbiota; and providing the derived food information to the subject.

[0075] In a preferred embodiment, in the step of acquiring information, information on the presence or amount of Parabacteroides bacteria is acquired from information on the intestinal bacterial flora, and in the step of deriving food information, information on a food that is a composition containing any one selected from sugar acid-containing oligosaccharides and salts thereof is derived based on the information on the presence or amount of Parabacteroides bacteria.

[0076] Such a method may further include displaying the provided food information on a target terminal, which may be, for example, a tablet terminal, a smartphone, or a personal computer.

[0077] [Cultivation method, etc.] In another aspect, there is provided a method for culturing Parabacteroides bacteria, characterized by using any one selected from sugar acid-containing oligosaccharides and salts thereof, or the use of any one selected from sugar acid-containing oligosaccharides and salts thereof in culturing Parabacteroides bacteria.

[0078] According to the inventors' studies, maltobionic acid and lactobionic acid promote the growth of Parabacteroides spp., but the addition of glucose, galactose, and gluconic acid, the constituent sugars of maltobionic acid and lactobionic acid, did not promote the growth of Parabacteroides spp. in fecal cultures. This is thought to be because, while the constituent sugars are utilized by other intestinal bacteria, the sugar acid-containing oligosaccharides are not utilized by other bacteria, but are preferentially utilized by Parabacteroides spp. Furthermore, the inventors have confirmed that when Parabacteroides spp. assimilates sugar acid-containing oligosaccharides, the sugar acid is not utilized but is excreted. Therefore, it is thought that Parabacteroides spp. can utilize only the sugars necessary for their own assimilation from aldonic acid-containing oligosaccharides that are difficult for other bacteria to utilize. Therefore, it is thought that not only maltobionic acid and lactobionic acid, but also sugars that can be assimilated by Parabacteroides spp., preferably sugars in which a monosaccharide is bound to a sugar acid, will achieve the desired effect.

[0079] The present invention will be described in more detail below using examples, although the technical scope of the present invention is not limited to these examples.

[0080] [Example 1] Feces was cultured in a medium containing maltobionic acid (Biosynth) and lactobionic acid (Fujifilm Wako Pure Chemical Industries, Ltd.), and the Parabacteroides were measured to confirm that the Parabacteroides were increased by maltobionic acid and lactobionic acid.

[0081] Feces from six individuals were cultured in filtered semi-solid medium for GAM glycolysis containing 0.3% (w / v) maltobionic acid and lactobionic acid at 37 °C under anaerobic conditions for 48 hours, followed by DNA extraction and meta-16S analysis. As a control, an equal volume of sterile water was used instead of the maltobionic acid and lactobionic acid solutions. DNA extraction was performed using a Maxwell® RSC Instrument (Promega), and meta-16S analysis was performed using a MiSeq (Illumina).

[0082] DNA extraction was performed using a Maxwell® RSC Instrument (Promega). For quantitative PCR, quantitative PCR was performed on DNA extracted from the culture medium in which the number of Parabacteroides bacteria had been measured in advance, and a standard curve was created. Quantitative PCR was performed on the DNA obtained above, and the number of Parabacteroides bacteria was calculated based on the standard curve. The results were then corrected to the number of bacteria per mL of culture medium. The primer sequences used for quantitative PCR are shown in the table below. DNA extracted from P. distasonis JCM5825T (the type species of Parabacteroides bacteria) was used as a standard.

[0083]

[0084] As a result, except for one fecal culture from a control where no Parabacteroides was detected, the proportion of Parabacteroides increased in all cultures compared to the control when maltobionic acid and lactobionic acid were added (Figure 1). These results demonstrate that maltobionic acid and lactobionic acid increase the number of Parabacteroides bacteria.

[0085] Example 2 Feces were cultured in a medium containing calcium maltobionate (Sanei Saccharification), and the parabacteroides were measured, confirming that calcium maltobionate increased the parabacteroides.

[0086] Feces from four individuals were cultured in filtered semi-solid medium for GAM saccharolysis containing 0.3% (w / v) calcium maltobionate at 37 °C under anaerobic conditions for 48 hours, followed by DNA extraction and quantitative PCR.

[0087] As a result, the addition of calcium maltobionate increased the number of Parabacteroides bacteria in all cultures compared to the control (Figure 2). These results indicate that calcium maltobionate also increases the number of Parabacteroides bacteria.

[0088] Example 3 Parabacteroides was cultured in a medium containing calcium maltobionate, and the turbidity of Parabacteroides was measured to confirm that the Parabacteroides bacteria were increased by calcium maltobionate.

[0089] Culture broths of P. distasonis JCM5825T, P. merdae JCM9497T, P. johnsonii JCM 13406T, P. goldsteinii JCM13446T, P. faecis JCM18682T, and P. acidifaciens JCM34233T stimulated in GAM medium were added to filtered GAM semi-solid medium containing 0.3% (w / v) calcium maltobionate at 1% and incubated at 37 °C under anaerobic conditions for 24 hours.

[0090] The results showed that the addition of calcium maltobionate increased the turbidity of Parabacteroides in all species compared to the control (Fig. 3). These results indicate that calcium maltobionate directly increases the number of Parabacteroides bacteria.

[0091] [Supplementary Example 1] Using a method similar to that used in Example 1, the growth-promoting effect of constituent sugars containing gluconic acid (aldonic acid) (the area surrounded by a solid line in the figure below), which is the common skeleton of maltobionic acid and lactobionic acid, on Parabacteroides genus bacteria was examined.

[0092]

[0093] As a result, the constituent sugars did not have a growth-promoting effect on Parabacteroides (data not shown). While the constituent sugars are utilized by other intestinal bacteria, the aldonic acid-containing oligosaccharides are not utilized by other bacteria, and are preferentially utilized by Parabacteroides.

[0094] We also confirmed that when Parabacteroides bacteria assimilate aldonic acid-containing oligosaccharides, the aldonic acid is not utilized but is excreted. Based on the results of the previous paragraph and these results, it is believed that Parabacteroides bacteria can utilize only the sugars they need for their own assimilation from aldonic acid-containing oligosaccharides that are difficult for other bacteria to utilize. Therefore, it is believed that the desired effect can be achieved not only with maltobionic acid and lactobionic acid, but also with any sugar in which a monosaccharide that can be assimilated by Parabacteroides is bound to an aldonic acid.

[0095] It was confirmed that the same effect was not observed with gluconic acid (aldonic acid), which has a common skeleton. Furthermore, when the growth-promoting effects of glucose and galactose on the Parabacteroides genus were examined using the same method as in the Examples, it was confirmed that maltobionic acid and lactobionic acid were superior (Figure 4).

[0096] [Supplementary Example 2] Parabacteroides distasoins JCM5825T and Parabacteroides merdae JCM9497T were cultured in filter-filtered (sterilized) semi-solid medium for GAM saccharolysis, or in filter-filtered (sterilized) semi-solid medium for GAM saccharolysis supplemented with glucose, maltobionic acid, or lactobionic acid. The culture was then centrifuged, and the supernatant was filter-sterilized to remove the bacterial cells. 1% F. prausnitzii NCIMB13872T, which had been stimulated and cultured in MRC medium, was added to the filter-sterilized culture medium and cultured under anaerobic conditions for 24 hours (see figure below). Turbidity during the culture was measured to evaluate the growth of F. prausnitzii.

[0097]

[0098] The results showed that the growth of F. prausnitzii NCIMB13872T was promoted in the culture supernatant of P. distasoins and P. merdae cultured in a medium containing maltobionic acid or lactobionic acid, more than in the control (culture supernatant of P. distasonis and P. merdae cultured in a medium lacking maltobionic acid or lactobionic acid) (Figs. 5 and 6).

[0099] [Summary] Another study by the present inventors has revealed that the addition of aldonic acid-containing oligosaccharides does not promote the growth of Faecalibacterium bacteria in test tube cultures (Faecalibacterium monoculture (pure) culture systems), rather than in fecal culture systems. Based on this finding and Supplementary Example 2, we believe that the growth of Faecalibacterium bacteria is promoted by the production of substances from maltobionic acid and lactobionic acid by Parabacteroides bacteria that promote the growth of Faecalibacterium bacteria.

[0100] Therefore, according to the present invention, it is possible to promote the growth of not only bacteria belonging to the genus Parabacteroides but also bacteria belonging to the genus Faecalibacterium, and the composition of the present invention can be used to promote the growth of bacteria belonging to the genus Parabacteroides and bacteria belonging to the genus Faecalibacterium.

[0101] Based on the above, aldonic acid-containing oligosaccharides, such as maltobionic acid, calcium maltobionate, and lactobionic acid, and their salts can be used to promote the growth of Parabacteroides bacteria, particularly in the intestine. Parabacteroides bacteria are known to produce acetic acid, succinic acid, and secondary bile acids in the intestine. Oral administration of Parabacteroides distasonis to ob / ob mice (a mouse model of type 2 diabetes and obesity) fed a high-fat diet has been reported to improve weight gain, glucose metabolism, and lipid metabolism. Furthermore, the succinic acid produced by Parabacteroides bacteria is known to improve glucose metabolism, thereby ameliorating obesity, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) (Non-Patent Documents 1 and 2). Furthermore, it is known that Parabacteroides bacteria are reduced in the intestines of people with psoriatic arthritis, inflammatory bowel disease, neonatal cholestasis, multiple sclerosis, non-alcoholic fatty liver disease, obesity, and metabolic syndrome (Non-Patent Document 3). Therefore, sugar acid-containing oligosaccharides, such as maltobionic acid, calcium maltobionate, and lactobionic acid, and their salts can be used to promote the growth of Parabacteroides bacteria, particularly in the intestine; to promote the production of acetic acid, succinic acid, and secondary bile acids in the intestine; to improve weight gain, glucose metabolism, and lipid metabolism; to improve lipid metabolism, glucose metabolism, and obesity; to treat any of psoriatic arthritis, inflammatory bowel disease, neonatal cholestasis, and multiple sclerosis; and to treat diseases or conditions that are improved by promoting the growth of Parabacteroides bacteria in the intestine.

[0102] [Production Example 1: Tablets] A tablet-type food composition for promoting the growth of Parabacteroides bacteria in the intestines is produced using calcium maltobionate according to the following formulation in a conventional manner.

[0103] Granulated sugar 718 parts, concentrated fruit juice 50 parts, citric acid 60 parts, flavoring 20 parts, gelatin 10 parts, calcium maltobionate 100 parts, calcium carbonate 15 parts, magnesium oxide 5 parts, potassium dihydrogen phosphate 22 parts

[0104] [Production Example 2: Powdered Drink] A prebiotic powdered drink is produced using calcium maltobionate according to the following formulation in a conventional manner.

[0105] Anhydrous crystalline glucose 650 parts, citric acid granules 60 parts, tartaric acid 60 parts, baking soda granules 55 parts, flavor 25 parts, calcium maltobionate 100 parts, dolomite 50 parts

[0106] [Production Example 3: Beverage] Using calcium maltobionate, the ingredients are mixed and dissolved in the following proportions, sealed in a container, and heated at 90°C for 5 minutes to obtain a beverage for promoting the growth of Parabacteroides bacteria in the intestines.

[0107] Calcium maltobionate 3 parts by weight, 5 times concentrated peach juice 2 parts by weight, sugar 5 parts by weight, citric acid 0.3 parts by weight, sodium citrate 0.05 parts by weight, water 89.65 parts by weight

[0108] The present invention supports the maintenance and improvement of people's health by providing a composition that promotes the growth of Parabacteroides bacteria. The present invention also provides a food composition and a method for producing a food that supports the maintenance and improvement of people's health. Furthermore, the present invention can improve the nutrition of various people, ensure healthy lifestyles, and promote welfare.

Claims

1. A composition for promoting the growth of bacteria belonging to the genus Parabacteroides, comprising any one selected from sugar acid-containing oligosaccharides and salts thereof.

2. The composition of claim 1, wherein the sugar acid is selected from aldonic acids, uronic acids, and aldaric acids.

3. The composition of claim 1, wherein the sugar acid is an aldonic acid.

4. The composition of claim 1, wherein the sugar acid is selected from gluconic acid, galactonic acid, xylonic acid, and arabinonic acid.

5. The composition of claim 1, wherein the sugar acid-containing oligosaccharide is a disaccharide.

6. The composition of claim 1, wherein the sugar acid-containing oligosaccharide is a disaccharide, and the monosaccharides constituting the disaccharide are selected from glucose, galactose, fructose, rhamnose, arabinose, mannose, and xylose.

7. The composition of claim 1, wherein the sugar acid-containing oligosaccharide is maltobionic acid or lactobionic acid.

8. The composition of claim 1, wherein the salt of the sugar acid-containing oligosaccharide is a calcium salt, magnesium salt, sodium salt, potassium salt, copper salt, iron salt, or zinc salt.

9. A composition according to any one of claims 1 to 8 for use as a prebiotic or synbiotic.

10. A composition for improving lipid metabolism, sugar metabolism, or obesity, comprising any one selected from sugar acid-containing oligosaccharides and salts thereof.

11. A composition for the treatment of any of psoriatic arthritis, inflammatory bowel disease, neonatal cholestasis, and multiple sclerosis, comprising any of sugar acid-containing oligosaccharides and salts thereof, the composition being for aiding in treatment.

12. The composition according to claim 10 or 11, wherein the sugar acid is an aldonic acid.

13. The composition according to claim 10 or 11, wherein the improvement and treatment is mediated by promoting the growth of bacteria belonging to the genus Parabacteroides in the intestine.

14. A composition for treating a disease or condition that is ameliorated by promoting the growth of bacteria belonging to the genus Parabacteroides in the intestine, comprising any one selected from sugar acid-containing oligosaccharides and salts thereof.

15. The composition of claim 14, wherein the sugar acid is an aldonic acid.

16. A method for culturing bacteria belonging to the genus Parabacteroides, characterized by using any one selected from sugar acid-containing oligosaccharides and salts thereof.

17. The culture method according to claim 16, wherein the sugar acid is an aldonic acid.

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