Composition for controlling the proliferation of butyric acid bacteria

Abstract

This invention provides a means for controlling butyrate production in the intestine. The objective of this invention is to provide a means for controlling the proliferation of butyrate-producing bacteria, represented by the genus *Faecalibacterium*. This invention provides a composition for controlling the proliferation of butyrate-producing bacteria, preferably *Faecalibacterium*, comprising any one selected from kohlbiose and oligosaccharides with kohlbiose as a constituent sugar. In one embodiment, the composition comprises galactosylkohlbiose as any one selected from kohlbiose and oligosaccharides with kohlbiose as a constituent sugar.

Description

Technical Field

[0001] This invention relates to compositions for controlling the proliferation of butyric acid bacteria, such as those of the genus Faecalibacterium. Background Technology

[0002] *Fegilebrium* bacteria are among the most common bacteria in the gut of healthy adults, possessing beneficial physiological functions such as butyrate production and anti-inflammatory activity. To date, reduced *Fegilebrium* levels in the gut have been reported in patients with inflammatory bowel diseases, including Crohn's disease and ulcerative colitis (Non-Patent Literature 1). Similar reports have also been made in patients with asthma, food allergies, non-alcoholic fatty liver disease, and chronic kidney disease (Non-Patent Literature 2-6, respectively). Furthermore, it has been confirmed that *Fegilebrium* levels are reduced in the gut of patients with irritable bowel syndrome (IBS) (Non-Patent Literature 7), inflammatory bowel disease (IBD) (Non-Patent Literature 8), Parkinson's disease (Non-Patent Literature 9), and cancer (Non-Patent Literature 10) compared to healthy individuals. Additionally, reports have shown that administration of this genus to IBD model mice improved symptoms such as weight loss and diarrhea (Non-Patent Literature 11), and that administration of this genus to Alzheimer's disease model mice improved cognitive impairment (Non-Patent Literature 12). Furthermore, it was reported that Faecalibacterium prausnitzii exhibited anti-inflammatory effects in cultured cell lines and TNBS colitis model mice (Non-Patent Literature 13).

[0003] Regarding bacteria of the genus *Aureobacterium*, 1-sucrose trisaccharide (Patent Document 1) is known as an effective ingredient for their proliferation.

[0004] On the other hand, kojibiose is known to promote the proliferation of Bifidobacteria (e.g., non-patent literature 14). In addition, patent literature 2 describes an in vivo lipid regulator containing one or more of kojibiose, kojitriose, kojibiose glucoside, kojitetraose, and kojitriose glucoside as active ingredients.

[0005] On the other hand, it was reported that in the fecal culture test system, kosperidone and 4'-galactosyl lactose did not cause the proliferation of Bacillus prednisevieriae (Non-Patent Literature 15, 16).

[0006] Furthermore, in studies using various isomers of glucose-disaccharides in a batch fermentation model of human coli, it was reported that the fermentation of disaccharide α(1-1) (trehalose) resulted in significantly higher butyrate production compared to other α-linked disaccharides containing trehalose (Non-Patent Literature 20). Moreover, it was reported that co-culturing of *Bifidobacterium adolescentis* L2-32 with *Faecalibacterium prausnitzii* S3 / L3 using fructooligosaccharides as a carbon source, and co-culturing with *F. prausnitzii* A2-165 using starch as a carbon source, resulted in higher butyrate concentrations in co-culture compared to monocultures of the respective *F. prausnitzii* species (Non-Patent Literature 21).

[0007] Existing technical documents

[0008] Patent documents

[0009] Patent Document 1: WO2017 / 159647 (Japanese Patent No. 6301024)

[0010] Patent Document 2: Japanese Patent Application Publication No. 2005-281188 (Japanese Patent No. 4746281)

[0011] Non-patent literature

[0012] Non-patent literature 1: Gastroenterol Res Pract. 2014; 2014:872725.

[0013] Non-patent literature 2: Allergol Immunopathol (Madr). 2019:47(4):365-371.

[0014] Non-patent literature 3: Int Arch Allergy Immunol. 2018;175(1-2):77-84

[0015] Non-patent literature 4: Nat Rev Gastroenterol Hepatol. 2020;17(5):279-297.

[0016] Non-patent literature 5: Genome Med. 2016:29;8(1):8.

[0017] Non-patent literature 6: Circ Res. 2022 Oct 14;131(9):e120-e134.

[0018] Non-patent literature 7: Gastroenterology. 2019;157(1):97-108.

[0019] Non-patent literature 8: Gut. 2014;63(8):1275-1283.

[0020] Non-patent literature 9: Microb Pathog. 2021;160:105187.

[0021] Non-patent literature 10: Bioengineered. 2021;12(1):7046-7060.

[0022] Non-patent literature 11: Mol Med Rep. 2019;20(1):25-32.

[0023] Non-patent literature 12: Cell Rep Med. 2021;2(9):100398.

[0024] Non-patent literature 13: Proc Natl Acad Sci US A. 2008;105(43):16731-16736.

[0025] Non-patent literature 14: Journal of agricultural and food chemistry. 2005, 53, 5192-5199.

[0026] Non-patent literature 15: Journal of functional foods, 2016, 20, 532-544

[0027] Non-patent literature 16: Appl Microbiol Biotechnol. 2013 Jul;97(13):5743-52

[0028] Non-patent literature 17: World J Gastroenterol. 2017:23(1): 60-75.

[0029] Non-patent literature 18: Front Nutr. 2022:9:1067647.

[0030] Non-patent literature 19: Nature 2013:504:446-450

[0031] Non-patent literature 20: Nutrients 2017:9(1):26

[0032] Non-patent literature 21: FEMS Microbiology Letters, 2015:362(21), fnv176 Summary of the Invention

[0033] The problem the invention aims to solve

[0034] Given the numerous reports demonstrating the close relationship between gut bacteria and health, it may be possible to reduce the risk of various diseases by controlling the proliferation of important bacteria.

[0035] On the other hand, butyric acid is expected to have inhibitory effects on fatty liver and obesity (Non-Patent Literature 17, 18), and it has been reported that increased butyric acid in the gut can suppress inflammation and other immune controls by increasing regulatory T cells (Non-Patent Literature 19). However, due to butyric acid's characteristic unpleasant odor, it is not recommended to ingest it directly, but rather to control its production in the gut. By utilizing prebiotics to control the proliferation of butyric acid bacteria in the gut, such as Bacillus faecalis, it is hoped that various diseases can be prevented and improved.

[0036] Solution for solving the problem

[0037] This invention provides the following content.

[0038] [1] A composition for controlling the proliferation of butyric acid bacteria, comprising any one selected from kojibiose and oligosaccharides with kojibiose as the constituent sugar.

[0039] [2] The composition according to 1, wherein the butyric acid bacteria is a bacterium of the genus Faecalibacterium.

[0040] [3] The composition according to 1 or 2 is used as a prebiotic or synbiotic.

[0041] [4] A composition for treating any of the following conditions: inflammation, asthma, food allergy, non-alcoholic fatty liver disease, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive impairment and atopic dermatitis, said composition comprising any of the following: kosperidin and oligosaccharides with kosperidin as the constituent sugar.

[0042] [5] The composition according to 4, wherein the treatment is carried out by means of controlling the proliferation of Bacillus spp.

[0043] [6] A composition for controlling butyrate production in the gut, comprising any one of kohlbiose and oligosaccharides with kohlbiose as the constituent sugar.

[0044] [7] The composition according to 6, wherein the production of butyric acid is controlled by controlling the proliferation of Bacillus foetida bacteria in the intestine.

[0045] [8] A composition for treating a disease or condition that can be improved by controlling the proliferation of Bacillus foetida bacteria in the gut, the composition comprising kohlbiose and an oligosaccharide with kohlbiose as the constituent sugar.

[0046] [9] The composition according to any one of 1 to 8, wherein the composition is obtained by acting a dextran sucrase on a raw material composition comprising lactose and sucrose.

[0047]

[10] The composition according to any one of 1 to 3, 5, 7 and 8, wherein controlling proliferation is promoting proliferation.

[0048]

[11] The composition according to any one of 1 to 3, 5, 7, 8 and 10, wherein the butyric acid bacteria or Faecalibacterium genus bacteria is Faecalibacterium prausnitzii.

[0049]

[12] The composition according to 6 or 7, wherein the butyric acid production is controlled to promote butyric acid production.

[0050]

[13] The composition according to any one of 1 to 12, wherein the composition comprises a substance having the ability to promote the proliferation of Parabacterium as any one selected from kosperidin and oligosaccharides with kosperidin as the constituent sugar.

[0051]

[14] The composition according to any one of 1 to 13, wherein the composition comprises galactosyl kosbiose as any one selected from kosbiose and oligosaccharides with kosbiose as the constituent sugar.

[0052]

[15] A method for providing food information, comprising the following steps:

[0053] Obtain information about the object's gut microbiota;

[0054] Based on gut microbiota information, information about the food provided to the recipient is derived; then...

[0055] Provide the exported food information to the object.

[0056] In the information acquisition process, information on the presence or quantity of *Bacillus* spp. is obtained from the gut microbiota information. In the food information derivation process, food information is derived based on the presence or quantity of *Bacillus* spp., wherein the food is a composition comprising any one of the groups selected from kohlbiose and oligosaccharides with kohlbiose as the constituent sugar.

[0057]

[16] A method for providing food information, comprising the following steps:

[0058] Obtain information about the amount of butyrate in the object's intestines;

[0059] Based on information about intestinal butyrate levels, information about the food provided to the recipients is derived; then...

[0060] Provide the exported food information to the object.

[0061] In the process of deriving information about a food, information about the food is derived based on information about the amount of butyrate in the intestine, wherein the food is a composition comprising any one of the groups selected from kosperidin and oligosaccharides with kosperidin as a constituent sugar.

[0062]

[17] A method for controlling the gut microbiota of a subject, or a method for supporting the subject’s diet or health, comprising the method described in 15 or 16, and including the step of providing food to the subject based on derived food information.

[0063]

[18] The method according to 15 or 16, wherein the food is used as a prebiotic or synbiotic.

[0064]

[19] The method according to any one of 16 to 18 further includes the step of displaying the provided food information on the terminal of the object.

[0065]

[20] Use for controlling the proliferation of Bacillus spp. in the gut microbiota, selected from any of kosbiose and oligosaccharides whose constituent sugar is kosbiose.

[0066]

[21] A composition for use in a method of controlling the proliferation of butyric acid bacteria, comprising any one selected from kohlbiose and oligosaccharides with kohlbiose as a constituent sugar. Use of any one selected from the group consisting of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar in the manufacture of a composition for controlling the proliferation of butyric acid bacteria. A method or non-therapeutic method for controlling the proliferation of butyric acid bacteria, comprising the step of administering a composition to a subject, said composition comprising any one selected from the group consisting of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar. Use or non-therapeutic use of a composition comprising any one selected from the group consisting of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar for controlling the proliferation of butyric acid bacteria.

[0067]

[22] The composition, manufacturing use, method or non-therapeutic use, or use or non-therapeutic use according to 21, wherein the butyric acid bacteria are bacteria of the genus Faecalibacterium.

[0068]

[23] The composition, manufacturing use, method or non-therapeutic use, or use or non-therapeutic use according to 21 or 22, wherein the composition is used as a prebiotic or synbiotic.

[0069]

[24] A composition for use in a method of treating any of the following conditions: inflammation, asthma, food allergy, non-alcoholic fatty liver disease, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive impairment, and atopic dermatitis, said composition comprising any of the following: kerbiose and oligosaccharides with kerbiose as a constituent sugar. Use of any of the following groups of kerbiose and oligosaccharides with kerbiose as a constituent sugar in the manufacture of a composition for treating any of the following conditions: inflammation, asthma, food allergy, non-alcoholic fatty liver disease, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive impairment, and atopic dermatitis. A method or non-therapeutic treatment for any of the following conditions: inflammation, asthma, food allergy, non-alcoholic fatty liver disease, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive impairment, and atopic dermatitis, comprising the step of administering a composition to a subject, said composition comprising any of the group consisting of crestigmastose and oligosaccharides with crestigmastose as a constituent sugar. Use or non-therapeutic use of a composition comprising any of the group consisting of crestigmastose and oligosaccharides with crestigmastose as a constituent sugar for the treatment of any of the following conditions: inflammation, asthma, food allergy, non-alcoholic fatty liver disease, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive impairment, and atopic dermatitis.

[0070]

[25] The composition, use in manufacture, method or non-therapeutic use, or use or non-therapeutic use according to 24, wherein the treatment is carried out by means of controlling the proliferation of Bacillus spp.

[0071]

[26] A composition for use in a method of controlling butyrate production in the intestine, comprising any one selected from kohlbiose and oligosaccharides with kohlbiose as a constituent sugar. Use of any one selected from the group consisting of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar in the manufacture of a composition for controlling butyrate production in the intestine. A method or non-therapeutic method for controlling butyrate production in the intestine, comprising the step of administering a composition to a subject, said composition comprising any one selected from the group consisting of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar. Use or non-therapeutic use of a composition comprising any one selected from the group consisting of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar for controlling butyrate production in the intestine.

[0072]

[27] The composition, manufacturing use, method or non-therapeutic use, or use or non-therapeutic use according to 26, wherein the control of butyric acid production is achieved by controlling the proliferation of Bacillus foetida bacteria in the intestine.

[0073]

[28] A composition comprising any one of kojibiose and oligosaccharides whose constituent sugars are kojibiose, for use in a method of treating a disease or condition that can be improved by controlling the proliferation of *F. coli* in the gut. Use of any one of kojibiose and oligosaccharides whose constituent sugars are kojibiose in the manufacture of a composition for treating a disease or condition that can be improved by controlling the proliferation of *F. coli* in the gut. A method or non-therapeutic method for treating a disease or condition that can be improved by controlling the proliferation of *F. coli* in the gut, comprising the step of administering to a subject a composition comprising any one of kojibiose and oligosaccharides whose constituent sugars are kojibiose. Use or non-therapeutic use of a composition comprising any one of kojibiose and oligosaccharides whose constituent sugars are kojibiose for treating a disease or condition that can be improved by controlling the proliferation of *F. coli* in the gut.

[0074]

[29] The composition, use in manufacture, method or non-therapeutic use, or use or non-therapeutic use according to any one of 21 to 28, wherein the composition is obtained by acting a dextran sucrase on a raw material composition comprising lactose and sucrose.

[0075]

[30] The composition, use in manufacture, method or non-therapeutic use, or use or non-therapeutic use according to any one of 21-23, 25, 27 and 28, wherein controlling proliferation is promoting proliferation.

[0076]

[31] The composition, use in manufacture, method or non-therapeutic use, or use or non-therapeutic use of any one of 21-23, 25, 27 and 28, wherein the butyric acid bacteria or Faecalibacterium genus bacteria is Faecalibacterium prausnitzii.

[0077]

[32] The composition, use in manufacture, method or non-therapeutic use, or use or non-therapeutic use according to any one of 21 to 31, wherein the composition comprises a substance having the ability to promote the proliferation of Parabacterium as any one selected from kosperidin and oligosaccharides with kosperidin as the constituent sugar.

[0078]

[33] The composition, use in manufacture, method or non-therapeutic use, or use or non-therapeutic use according to any one of 21 to 31, wherein the composition comprises galactosyl kosbiose as any one selected from kosbiose and oligosaccharides with kosbiose as the constituent sugar.

[0079]

[34] A method for controlling the proliferation of *Bacillus* bacteria in the gut microbiota, comprising the step of making the gut microbiota containing *Bacillus* bacteria contain any one of kohlbiose and oligosaccharides with kohlbiose as the constituent sugar.

[0080] The effects of the invention

[0081] By using any of the oligosaccharides selected from kojibiose and kojibiose as constituent sugars as prebiotics, butyric acid bacteria, represented by Bacillus faecalis, can be increased in the gut. Furthermore, by increasing butyric acid bacteria in the gut, the prevention and improvement of various diseases can be expected. Attached Figure Description

[0082] [ Figure 1 [Changes in the occupancy of *Bacillus* bacteria in V3-V4 region amplicon sequencing based on MiSeq (Illumina) in a human fecal culture system, induced by galactosyltrisaccharide (trisaccharide fraction). Black dots represent the progression of individual subjects, and horizontal lines represent the mean.]

[0083] [ Figure 2 Chromatograms of the enzyme reaction solution and the trisaccharide and tetrasaccharide fractions after fractionation and purification.

[0084] [ Figure 3 The effect of culture supernatant of Parabacteroides distasoins or Parabacteroides merdae on the proliferation control of Faecalibacterium prausnitzii.

[0085] [ Figure 4 The effect of culture supernatant of *Pseudomonas dell'sii* or *Pseudomonas faecalis* on the proliferation control of *F. hattorii*, *F. longum*, *F. gallinarum*, and *F. butyricigenerans*. Detailed Implementation

[0086] This embodiment relates to a composition for controlling the proliferation of butyric acid bacteria, represented by Bacillus foetida, using kojibiose and oligosaccharides with kojibiose as the constituent sugar as active ingredients.

[0087] [Active Ingredients]

[0088] The composition of this embodiment comprises any one selected from the group consisting of kojibiose and oligosaccharides with kojibiose as a constituent sugar as an active ingredient. When referring to oligosaccharides with kojibiose as a constituent sugar, kojibiose itself is not included. It should be noted that, in relation to this invention, the term "any one" is used to mean "at least one," unless specifically stated otherwise. For example, "any one selected from the group consisting of kojibiose and oligosaccharides with kojibiose as a constituent sugar" includes not only kojibiose, only one type of oligosaccharide with kojibiose as a constituent sugar, but also kojibiose and one type of oligosaccharide with kojibiose as a constituent sugar, two types of oligosaccharides with kojibiose as a constituent sugar, etc. "Comprising...as an active ingredient" means that it is used in the composition in an effective amount to achieve the target function, or that it is clearly indicated by labeling as contributing to achieving the purpose. In functionally labeled foods, the active ingredient sometimes refers to a functionally related ingredient (meaning an ingredient that contributes to a specific health purpose (excluding ingredients related to reducing disease risk)).

[0089] There are no particular limitations on the kojibiose and oligosaccharides with kojibiose as the constituent sugar used in the composition, as long as they have the target effect. In addition, the kojibiose and oligosaccharides with kojibiose as the constituent sugar used in the composition can be one type or a combination of two or more types.

[0090] Examples of oligosaccharides with sucralose as a constituent sugar include galactosyl sucralose, sucralose trisaccharide, selaginose (sucralose glucoside), centose, sucralose glycoside, tetrasaccharides formed by linking one molecule of glucose or other monosaccharides to these trisaccharides, sucralose tetrasaccharide, and sucralose trisaccharide glucoside.

[0091] In a preferred embodiment, the composition comprises either kosbiose or galactosylkosbiose. Examples of such compositions include compositions comprising kosbiose, compositions comprising galactosylkosbiose, compositions comprising kosbiose and galactosylkosbiose, and compositions comprising kosbiose, galactosylkosbiose, and a tetrasaccharide having one glucose molecule attached to the galactosylkosbiose.

[0092] In this invention, the term "galactosyl kerbiose," unless otherwise specified, refers to a substance in which galactose is attached to any position from 1 to 8 of the kerbiose group by an α- or β-bond. Theoretically, there are four possible linkages of galactose to the OH group at position 8: α-α, α-β, β-α, and β-β. There are two possible linkages of galactose to the OH groups at positions 2 to 7. Therefore, it is envisioned that there are 18 types of galactosyl kerbiose, respectively named 8α-α kerbiose, 8α-β kerbiose, 8β-α kerbiose, 8β-β kerbiose, 1α kerbiose, 2β kerbiose, 2α kerbiose, 2β kerbiose, 3α kerbiose, 3β kerbiose, 4α kerbiose, 4β kerbiose, 5α kerbiose, 5β kerbiose, 6α kerbiose, 6β kerbiose, 7α kerbiose, and 7β kerbiose.

[0093]

[0094] In one embodiment, the composition comprises any one of 18 galactosyl quinoline, namely any one of 8α-α-quinoline, 8α-β-quinoline, 8β-α-quinoline, 8β-β-quinoline, 1α-quinoline, 2β-quinoline, 2α-quinoline, 2β-quinoline, 3α-quinoline, 3β-quinoline, 4α-quinoline, 4β-quinoline, 5α-quinoline, 5β-quinoline, 6α-quinoline, 6β-quinoline, 7α-quinoline, and 7β-quinoline, and may contain 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18.

[0095] In a preferred embodiment, the galactosyl disaccharide contained in the composition is α-D-glucopyranosyl-(1→2)-[β-D-galactopyranosyl-(1→4)-]D-glucopyranoside. This sugar can also be referred to as a type of glucosyllactose.

[0096] According to the research of the inventors, galactosyl kohlbiose has been confirmed to have excellent effects in controlling the proliferation of *Bacillus* spp., a type of butyric acid bacterium. Here, galactosyl kohlbiose is an oligosaccharide containing kohlbiose as a constituent sugar, which, after being administered to a subject, can be broken down by lactase in the subject's digestive tract to produce kohlbiose. Therefore, if kohlbiose is used as a constituent sugar, kohlbiose is also produced in the intestine, achieving the same effect as galactosyl kohlbiose.

[0097] In another preferred embodiment, the composition comprises any one of kojibiose and oligosaccharides with kojibiose as a constituent sugar and has the ability to promote the proliferation of *Pseudomonas* bacteria.

[0098] Parabacterium bacteria are among the most common bacteria in the gut of healthy adults. According to the present inventors, culturing *Femtobacter* bacteria, a type of butyric acid bacterium, in the culture supernatant of *Parabacterium* bacteria promoted their proliferation compared to culturing in fresh culture medium. Therefore, it can be said that by promoting the proliferation of *Parabacterium* bacteria, it is possible to control the proliferation of butyric acid bacteria such as *Femtobacter* bacteria. It should be noted that the present inventors have further confirmed that kosperidin and oligosaccharides with kosperidin as a constituent sugar promote the proliferation of *Parabacterium* bacteria (PCT / JP2023 / 030455). Furthermore, other experiments have also shown that the proliferation of *Femtobacter* bacteria can be controlled by promoting the proliferation of *Parabacterium* bacteria (application pending).

[0099] According to the research of the inventors, among kohlbiose and oligosaccharides with kohlbiose as a constituent sugar, kohlbiose and galactosylkohlbiose promote the proliferation of *Parabacterium* bacteria. Other oligosaccharides with kohlbiose as a constituent sugar that promote the proliferation of *Parabacterium* bacteria can be determined according to the steps described later for evaluating whether a certain component controls the proliferation of *Femtobacter* bacteria in the intestine.

[0100] In one embodiment, the composition comprises any one of kojibiose and oligosaccharides with kojibiose as a constituent sugar, and a substance that promotes the proliferation of any one of the genus *P. distasonis* and *P. merdae*, preferably *P. distasonis*.

[0101] The source and preparation method of kojibiose and oligosaccharides with kojibiose as the constituent sugar used in this invention are not particularly limited, and they can be manufactured by any method such as fermentation, enzymatic method, or organic synthesis. As one preferred manufacturing method, one example includes the following steps: acting a raw material composition containing lactose and sucrose with dextran sucrase or lactic acid bacteria expressing dextran sucrase or their treatments to obtain a composition containing galactosyl kojibiose. In this invention, dextran sucrase, unless specifically described, refers to an enzyme belonging to the glycoside hydrolase family 70 (GH70) (see (CAZy) databases and Cantalel et al., Nucleic Acids Res. 37:D233-238, 2009).

[0102] When using lactic acid bacteria, lactic acid bacteria expressing glucan sucrase are preferred. Preferred examples of lactic acid bacteria are those belonging to the Leuconostoc family, more preferably to the Leuconostoc genus, and even more preferably Leuconostoc mesenteroides.

[0103] When using lactic acid bacteria, lactic acid bacteria that stably express glucan sucrase are preferred. Preferred examples of lactic acid bacteria are those belonging to the family Lactobacillaceae, more preferably those belonging to the genus *Liquorilactobacillus* or *Limosilactobacillus*, and even more preferably *Limosilactobacillus reuteri* or *Liquorilactobacillus satsumensis*.

[0104] When using lactic acid bacteria, lactic acid bacteria that stably express glucan sucrase are preferred, and glucan sucrase is more preferably cell-bound. Preferred examples of lactic acid bacteria are those belonging to the family Lactobacillaceae, more preferably to the genus Liquorylatobacillus, and even more preferably to Liquorilactobacillus satsumensis. A particularly preferred example of a strain of Liquorilactobacillus satsumensis is JCM12392. It should be noted that JCM12392 is described as Lactobacillus satsumensis in RIKEN BioResource Center, GENERAL CATALOG No. 9, 2012, JAPAN COLLECTION OF MICROORGANISMS, M51.

[0105] It should be noted that, regarding this invention, when describing lactic acid bacteria, unless otherwise specified, the classification is based on the reclassification of Zheng J, Wittouck S, Salvetti E, Franz CMAP, Harris HMB, Mattarelli P, O'Toole PW, Pot B, Vandamme P, Walter J, Watanabe K, Wuyts S, Felis GE, Ganzle MG, Lebeer S.: A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol. 2020 Apr; 70(4): 2782-2858. If classified according to the pre-reclassification, *Lactobacillus satsumensis* would be classified as *Lactobacillus satsumensis*.

[0106] The lactic acid bacteria expressing glucan sucrase or their treatments are preferably any species selected from the group consisting of live cells, dead cells, cultures containing cells, cell fragments, and purified glucan sucrase.

[0107] Glucan sucrase used to produce kojibiose and oligosaccharides with kojibiose as the constituent sugar, or lactic acid bacteria expressing koji sucrase, or their treatment products, can be prepared by transformation, chemical synthesis, or genome editing technologies.

[0108] The composition containing galactosyl kerbiose obtained by this manufacturing method can be used directly as a solution containing kerbiose and an oligosaccharide with kerbiose as the constituent sugar, or it can be used after purification with an ion exchange resin or the like. That is, the composition of the present invention can be a composition containing galactosyl kerbiose obtained by acting a composition containing sucrose and lactose with dextran sucrase or lactic acid bacteria expressing dextran sucrase or their treatment.

[0109] [use]

[0110] (Function / Effect / Effect)

[0111] The composition of this embodiment can be used to control the proliferation of butyric acid bacteria. In this invention, butyric acid bacteria refers to bacteria that are beneficial bacteria (bacteria useful for health) and can produce butyric acid in the intestine. Butyric acid bacteria are sometimes also referred to as butyrate-producing bacteria. In a preferred embodiment, the composition can be used to control the proliferation of butyric acid bacteria in the human intestine. Controlling the proliferation of butyric acid bacteria in the human intestine means controlling the proliferation of butyric acid bacteria in the presence of various bacteria in the human intestine (sometimes also called gut microbiota). In this invention, when referred to as gut microbiota, it means the community of various bacteria residing in the intestine, including, for example, the community of bacteria contained in feces, but not limited to the community of bacteria located in the intestine. In this invention, control includes upward control (sometimes also called promotion, increase) and downward control (sometimes also called inhibition, decrease), preferably upward control. The control of proliferation can be the control of the number of bacteria or the control of the occupancy rate described later.

[0112] In this invention, the intestine refers to the digestive organ in humans and animals where bacteria reside and digest / absorb ingested food. The intestine includes the small intestine and the large intestine, preferably the large intestine.

[0113] In one manner, the composition is used to control the proliferation of butyric acid bacteria selected from any of the following: bacteria belonging to the genus *Coprococcus*, bacteria belonging to the genus *Clostridium*, bacteria belonging to the genus *Eubacterium*, bacteria belonging to the genus *Roseburia*, bacteria belonging to the genus *Butyrivibrio*, bacteria belonging to the genus *Anaerostipes*, bacteria belonging to the genus *Subdoligranulum*, bacteria belonging to the genus *Anaerotruncus*, bacteria belonging to the genus *Ruminococcus*, bacteria belonging to the genus *Shuttleworthia*, bacteria belonging to the genus *Lachnospira*, bacteria belonging to the genus *Megashpaera*, and bacteria belonging to the genus *Butyricicoccus*.

[0114] Alternatively, in another embodiment, the composition is used to control the proliferation of any species selected from the following bacteria. The following are the main butyric acid bacteria isolated from the human coli:

[0115] Faecalibacterium prausnitzii, Faecalibacterium longum, Faecalibacterium butyricigenerans, Faecalibacterium hattorii, and Faecalibacterium duncaniae.

[0116] Eubacterium lomosum, Eubacterium rectale

[0117] Roseburia intestinalis, Roseburia faecis, Roseburia hominis, Roseburia inulinivorans, and Roseburia ceccicola.

[0118] Butyrivibrio fibrisolvens, Butyrivibrio crossotus, Butyrivibrio proteoclasticus

[0119] Eubacterium ramulus, Eubacterium hallii

[0120] Anaerobic bacterium californicum (Anaerostipes caccae), butyrate-producing anaerobic bacterium (Anaerostipes butyraticus), anaerobic bacterium handrus (Anaerostipes handrus), rhamnosivorans (Anaerostipes rhamnosivorans), SSC / 2, SS2 / 1, SS3 / 4, GM2 / 1,

[0121] Regular coccidia (Coprococcus catus), associated coccidia (Coprococcus eutactus), and clever coccidia (Coprococcus comes)

[0122] Eubacterium cylindroides

[0123] Rare variant of Subdoligranulum variabile

[0124] Human colonic anaerobic bacteria (Anaerotruncus colihominis)

[0125] Clostridium acetobutylicum, Clostridium butyricum, Clostridium saccharobutylicum, Clostridium tyrobutyricum, Clostridium hathewayi, Clostridium indolis, Clostridium nexile, Clostridium symbiosum, and Clostridium orbiscidens.

[0126] Active rumenococcus (Ruminococcus gnavus), ovomucoccus (Ruminococcus obeum)

[0127] Shuttleworthia satelles

[0128] Lachonpira multipara, Lachnospira eligens, Lachonpira multiparis, Lachnospira pectinoschiza

[0129] Megasphaera elsdenii,

[0130] Butyricicoccus pullicaecorum (chicken cecum butyricococcus)

[0131] In a preferred embodiment, the composition is used to control the proliferation of bacteria belonging to the genus *Fecobacterium* (sometimes simply referred to as *Fecobacterium* bacteria) in the intestine. It should be noted that, in the following description of the invention, embodiments, and examples, *Fecobacterium* bacteria from the butyric acid bacteria genus are sometimes used as examples; however, those skilled in the art can understand that this description can be applied to other butyric acid bacteria.

[0132] Examples of bacteria in the genus *Bacillus* include the following:

[0133] Prevotella coccidioides;

[0134] Duncan's coccidioidomyces

[0135] Long-lived coccidia

[0136] Butyric acid-producing cocci

[0137] Divine Bacillus foetida,

[0138] As a bacterium of the genus *Cercobacterium*, *Cercobacterium prevalens* is preferred.

[0139] In this invention, when referring to bacteria of the genus *Bacillus*, it means bacteria identified as belonging to the genus *Bacillus* through molecular systematic analysis based on the 16S rRNA gene. The criteria for determining the genus based on molecular systematic analysis of 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).

[0140] In this invention, controlling the proliferation of specific bacteria in the bacterial community refers to controlling the proportion (occupancy rate) of specific bacteria in the bacterial community.

[0141] Whether a component controls the proliferation of *Bacillus faecalis* bacteria in the gut can be evaluated as follows: Fecal samples containing *Bacillus faecalis* from healthy individuals are added to an appropriate culture medium and incubated for the desired time. The component to be evaluated is then added, and the culture is continued under appropriate conditions (e.g., 37°C, anaerobic conditions, similar to intestinal conditions, for 48 hours). The number of *Bacillus faecalis* bacteria in the culture is then determined. Furthermore, the results can be compared with those of cultures incubated under the same conditions but differing only in the addition of a control (e.g., sterile water) instead of the component to be evaluated.

[0142] The number of *Bacillus* bacteria in the bacterial community can be determined using known methods. One preferred method is 16S metagenomic analysis (16S rRNA gene amplicon sequence analysis) of DNA extracted from the culture. DNA extraction for 16S metagenomic analysis can be performed using commercially available kits. There are no particular restrictions on the genomic region analyzed, as long as it is sufficient to identify the bacteria; the V3-V4 region of the 16S rRNA gene can be used. Primers, amplification conditions, amplicon purification, and other methods used for bacterial analysis can also be employed using methods well-known to those skilled in the art. Sequence interpretation is preferably performed using a higher-performance next-generation sequencer. QIIME 2 can be used in the analysis of the obtained data. TM Next-generation microbial informatics platforms, etc. Regarding 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. JVis Exp. 2014;(90):51709. Published 2014 Aug 29. doi:10.3791 / 51709.

[0143] In one embodiment, the composition can be used to treat any of the following conditions: inflammation, asthma, food allergy, non-alcoholic fatty liver disease, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive impairment, and atopic dermatitis. Treatment is not limited to controlling the proliferation of *Femtobacter* bacteria in the gut, except where specifically described.

[0144] *Fegilebrium* bacteria are among the most common bacteria in the gut of healthy adults, possessing beneficial physiological functions such as butyrate production and anti-inflammatory activity. Furthermore, a reduction in *Fegilebrium* in the gut has been reported in patients with inflammatory bowel diseases, including Crohn's disease and ulcerative colitis (Non-Patent Literature 1). Similar reports have been made in patients with asthma, food allergies, non-alcoholic fatty liver disease, and chronic kidney disease (Non-Patent Literature 2-6, respectively). Moreover, it has been confirmed that *Fegilebrium* bacteria are reduced in the gut of patients with irritable bowel syndrome (IBS) (Non-Patent Literature 7), inflammatory bowel disease (IBD) (Non-Patent Literature 8), Parkinson's disease (Non-Patent Literature 9), and cancer (Non-Patent Literature 10) compared to healthy individuals. Additionally, administration of this genus to IBD model mice has been reported to improve symptoms such as weight loss and diarrhea (Non-Patent Literature 11), and administration of this genus to Alzheimer's disease model mice has been reported to improve cognitive impairment (Non-Patent Literature 12). Furthermore, it has been reported that *Faecalibacterium prausnitzii* exhibits anti-inflammatory effects in cultured cell lines and TNBS colitis model mice (Non-Patent Literature 13). Therefore, in one embodiment, the composition can be used for intestinal inflammation by controlling the proliferation of *Faecalibacterium* bacteria in the intestine; additionally, in another embodiment, it can be used for Crohn's disease and inflammatory bowel disease by controlling the proliferation of *Faecalibacterium* bacteria in the intestine. Inflammatory bowel diseases include ulcerative colitis and Crohn's disease. Furthermore, in another embodiment, the composition can be used for any disease or state selected from asthma, food allergy, non-alcoholic fatty liver disease, chronic kidney disease, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), Parkinson's disease, cancer, symptoms such as weight loss and diarrhea associated with IBD, cognitive impairment in Alzheimer's disease, and inflammation by controlling the proliferation of *Faecalibacterium* bacteria in the intestine.

[0145] When used for anti-inflammatory purposes or for the treatment of inflammatory bowel disease, the composition may be configured without any of the following:

[0146] Oligosaccharides (e.g., raffinose, stachyose, galacto-oligosaccharides, isomaltooligosaccharides, lactulose, lactulose, xylooligosaccharides, agaro-oligosaccharides, mannan-oligosaccharides, or fructo-oligosaccharides), inulin, pectin, pectin processed products, guar gum, guar gum decomposition products, psyllium gum, ebony gum, tragacanth gum, gum arabic, indigestible starch, indigestible dextrin, polydextrose, cellulose, hemicellulose, soybean polysaccharides, β-glucan, glucomannan, galacto-mannan, chondroitin sulfate, hyaluronic acid, fructan, lignin, alginic acid and its salts, agarose, and chitosan.

[0147] When used for anti-inflammatory purposes, or for the treatment of inflammatory bowel disease, the composition may contain any oligosaccharide selected from glycoacids and their salts as the active ingredient, but not any other oligosaccharides.

[0148] In addition, the composition can be used to treat diseases or conditions that can be improved by controlling the proliferation of *Bacillus faecalis* bacteria in the gut. Various diseases or conditions can be considered as such.

[0149] The composition of this embodiment can also be used to control butyrate production in the intestine, and preferably to promote butyrate production. In a preferred embodiment, the composition controls butyrate production by controlling the proliferation of *Bacillus foetida* bacteria in the intestine.

[0150] By measuring the butyrate concentration in feces from healthy individuals who have ingested a certain component and comparing it with an appropriate control as needed, it is possible to determine whether the component can control butyrate production in the intestine. Alternatively, feces from healthy individuals can be added to an appropriate culture medium and cultured for a specified period. Then, the component to be evaluated can be added and cultured under appropriate conditions (e.g., 37°C, anaerobic conditions, 48 ​​hours, similar to intestinal conditions). The butyrate concentration in the culture can then be measured. Furthermore, the results can be compared with those of cultures that differ only in the addition of a control (e.g., sterile water, a substance known not to control butyrate production) but are cultured under identical conditions. The method for determining butyrate in the analyte can be appropriately determined based on the analyte and the butyrate concentration; for example, it can be performed using HPLC, gas chromatography, etc.

[0151] Butyric acid is one of the short-chain fatty acids found in the intestine. Butyric acid is expected to have inhibitory effects on fatty liver and obesity (Non-Patent Literature 17, 18). Furthermore, increased butyric acid in the intestine has been reported to have effects on immune control, such as inflammation suppression through increased regulatory T cells (Non-Patent Literature 19). Therefore, the compositions of the present invention can be used to treat diseases or conditions that can be prevented or improved by increasing butyric acid in the intestine, or diseases or conditions caused by decreased butyric acid in the intestine, and can also be used for fatty liver suppression, obesity suppression, and immune control.

[0152] Regarding the present invention, when referring to the management of a disease or condition, it includes reducing the risk of developing the disease, delaying the onset of the disease, prevention, treatment, cessation, and postponement. Furthermore, management includes maintaining a normal or desired state, maintaining capacity, and alleviating symptoms (preferably temporary symptom relief). Moreover, management includes contributing to the improvement of a disease or condition, alleviating a disease or condition, and reducing the risk of developing a disease or condition. Treatment includes radical treatment (treatment that eliminates the cause) and symptomatic treatment (treatment that improves symptoms). Actions for improvement or management include medical actions performed by doctors and nurses, midwives, etc., under the guidance of doctors, and non-medical actions performed by persons other than doctors, such as pharmacists, nutritionists (including managed nutritionists and sports nutritionists), health care workers, midwives, nurses, clinical laboratory technicians, exercise instructors, pharmaceutical manufacturers, pharmaceutical distributors, food manufacturers, and food distributors. Alternatively, it includes individuals recommended by computer programs to consume foods, drinks, or medications that can control Fusobacterium bacteria. Furthermore, prevention or reduction of the risk of disease includes recommendations for the intake of specific foods and nutritional guidance (including guidance on nutrition needed for the recovery of the injured and sick, and guidance on nutrition for maintaining and promoting health).

[0153] (object)

[0154] The composition of this embodiment is suitable for administration to: subjects who wish to or need to control the proliferation of butyric acid bacteria, preferably *Bacillus faecalis*, in the gut; subjects who wish to or need to control butyric acid production in the gut; subjects whose diseases or conditions can be prevented or improved by increasing butyric acid in the gut; subjects suffering from diseases or conditions caused by decreasing butyric acid in the gut; subjects with fatty liver or at risk of fatty liver; subjects with obesity or at risk of obesity; subjects who wish to or need immune control; subjects who wish to or need anti-inflammatory treatment of the gut; subjects with inflammatory bowel disease or at risk of inflammatory bowel disease; and subjects whose diseases or conditions can be improved by controlling the proliferation of *Bacillus faecalis* in the gut. Examples of subjects who wish to or need to control the proliferation of *Bacillus faecalis* include those with inflammatory bowel disease, allergies (asthma), food allergies, non-alcoholic fatty liver disease, chronic kidney disease, and dementia.

[0155] The objects for which the proliferation of butyric acid bacteria, preferably Bacillus spp., in the gut is desired or necessary to be controlled include those in which butyric acid bacteria, preferably Bacillus spp., are detected in at least one of the gut and feces, or those in which the amount of butyric acid in the gut is low. In addition, the objects for which the proliferation of butyric acid bacteria, preferably Bacillus foetida, in the gut is desired or needed to be controlled include: objects considered to have a low number or prevalence of butyric acid bacteria, preferably Bacillus foetida, in the gut through any examination / analysis such as intestinal flora (microbiota) examination, fecal substance examination, and fecal metabolomics analysis; or objects considered to have a low amount of butyric acid in the gut; objects considered to be at high risk of any of the following: inflammation, asthma, food allergy, non-alcoholic fatty liver disease, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive decline, and atopic dermatitis; and objects for which dietary foods or drugs that are recommended to control the proliferation of butyric acid bacteria, preferably Bacillus foetida, in the gut are recommended based on the results of examinations / analysis and through the judgment of doctors, nurses, pharmacists, nutritionists, etc., or through the judgment of computer programs.

[0156] Objects in which at least one of the intestines and feces is found to have a low number or occupancy of *Bacillus foetida* bacteria include, for example, cases where a culture containing feces collected from the object is cultured at 37°C under anaerobic conditions for 24 hours, and the occupancy of *Bacillus foetida* bacteria in the culture is less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, or less than 0.3%.

[0157] In one approach, the object is a healthy person (not diagnosed with a disease by a doctor). The object can be a human or an animal other than a human.

[0158] There are no specific age restrictions for the eligible participants. Eligible participants include newborns (within 28 days after birth); infants (less than 1 year after birth); toddlers (1-6 years after birth); children (7 years and older but less than 15 years old); adults (15 years and older); and those 65 years and older.

[0159] [Composition]

[0160] (Food compositions, etc.)

[0161] The compositions of this invention can be food compositions or pharmaceutical compositions. Unless otherwise specified, food and pharmaceuticals include not only foods and pharmaceuticals for human use, but also foods and pharmaceuticals for animals other than humans. Unless otherwise specified, food includes general foods, functional foods, nutritional compositions, and includes therapeutic foods (foods intended to achieve therapeutic purposes; foods prepared based on menus prescribed by nutritionists or others according to dietary prescriptions issued by doctors), dietary therapy foods, ingredient-adjusted foods, nursing foods, and therapeutic support foods. Unless otherwise specified, food includes not only solids but also liquid substances, such as beverages, drinks, liquids, and soups. Functional foods refer to foods that can impart specified functions to organisms, including foods for specific health purposes (including conditional [foods for specific health purposes]), functionally labeled foods, health foods including nutritional functional foods, foods for special purposes, nutritional supplements, health supplements, supplements (e.g., tablets, coated tablets, sugar-coated tablets, enteric-coated preparations, capsules (enteric-coated soft capsules, enteric-coated hard capsules, colon-delivered capsules, etc.), liquids, and other dosage forms), dietary supplements, food supplements, medical foods (as defined by the U.S. Food and Drug Administration (FDA)), beauty foods (e.g., weight-loss foods), and all other health foods. Furthermore, in this invention, "functional foods" includes health foods that make health claims based on food standards from the Codex Alimentarius Commission (FAO / WHO Joint Committee on Food Standards). Food supplements refer to substances that supplement ordinary foods, either alone or in combination, by concentrating nutrients or other substances with nutritional or physiological effects, and are listed as food supplements in the product description. Nutritional supplements are products intended to supplement the diet (excluding tobacco), containing one or more target ingredients, and are listed as nutritional supplements on the product label. The composition may sometimes be a purified form of a specific sugar. Purified forms include fractionated products, partially purified products, and crude purified products. It should be noted that actual labeling on food products follows the labeling laws of each country.

[0162] (Provide assistance, etc.)

[0163] The compositions of the present invention can be administered orally, or non-orally, such as via a tube (gastric fistula, intestinal fistula), or via the nose, with oral administration being preferred. Regarding the present invention, administration is used not only for administering the medicine to the subject, but also for ingesting food or other substances other than the medicine. "(Perform) administration" can be replaced with "(Perform) ingestion," and "(Make) ingestion" can be replaced with "(Perform) administration."

[0164] The composition can be administered to the subject repeatedly or continuously for a long period of time. There is no particular time limit, but to fully confirm the effect, it can be administered continuously for a relatively long period of time, such as more than 3 days, more than 1 week, more than 2 weeks, more than 1 month, more than 3 months, more than 6 months, or more than 1 year.

[0165] The composition can be administered daily, or in advance when there is a high risk, or when a need arises. The composition can be given as food, or before, after, or between meals, or when a disease or condition that the composition is desired to improve occurs.

[0166] (Dosage, content)

[0167] In this embodiment, any of the active ingredients selected from kojibiose and oligosaccharides with kojibiose as a constituent sugar can be used in amounts permitted for food or pharmaceutical purposes. Furthermore, the dosage of the composition of this embodiment is only required to achieve the desired effect. The dosage can be appropriately set considering various factors such as the subject's age, weight, and symptoms.

[0168] The daily dosage of the composition can be set as an amount permitted for food or medicine. Furthermore, the amount of active ingredient can be 0.5g or more, 1g or more, preferably 2g or more, more preferably 3g or more, more preferably 5g or more, and even more preferably 10g or more. The upper limit of the daily active ingredient dosage, while having any lower limit, can be set to 80g or less, 70g or less, 60g or less, 50g or less, 40g or less, 30g or less, 20g or less, or 15g or less. It should be noted that when the composition contains multiple active ingredients, the amount of active ingredient refers to the total amount of active ingredients contained therein.

[0169] The administration can be once a day or divided into multiple administrations per day, such as 2 to 10 times. The dosage of the active ingredient in each administration can be set to 0.5g or more, 1g or more, preferably 2g or more, more preferably 3g or more, and even more preferably 5g or more. While the lower limit is arbitrary, the upper limit of the active ingredient in each administration can be set to less than 70g, less than 60g, less than 50g, less than 40g, less than 30g, less than 25g, or less than 10g.

[0170] The content of the active ingredient in the composition can be set to an amount permissible for food or pharmaceutical purposes, and can also be appropriately set according to the form of the composition. For example, when the composition is in the form of fermented milk or beverage for direct consumption, the content of the active ingredient per 100g of the composition can be set to 0.01% or more, preferably 0.1% or more, more preferably 0.3% or more, and even more preferably 0.5% or more. The upper limit of the active ingredient per 100g of the composition can be set to 8% or less, 5% or less, 4% or less, or 3% or less, provided the lower limit is arbitrary. Alternatively, the content of the active ingredient in the solid component of each part of the composition can be set to 0.1% or more, preferably 1% or more, more preferably 3% or more, and even more preferably 5% or more. The upper limit of the active ingredient in each solid component can be set to 80% or less, 50% or less, 40% or less, or 30% or less, provided the lower limit is arbitrary. It should be noted that, in the context of this invention, unless specifically stated otherwise, % refers to mass.

[0171] (Other ingredients, additives)

[0172] Regarding this invention, the composition may also contain other active ingredients or nutritional components permitted as food or pharmaceuticals. Examples of such ingredients include lipids (e.g., milk fat, vegetable oils, oils containing medium-chain fatty acids), proteins (e.g., milk proteins, 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), and other components. Sugars other than disaccharides and oligosaccharides whose main component is disaccharide (glucose, sucrose, fructose, maltose, trehalose, erythritol, maltitol, palaginose, 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 niacin), minerals (e.g., copper, zinc, iron, cobalt, manganese), antibiotics, dietary fiber, etc.

[0173] Regarding this invention, the composition may contain prebiotics in addition to the active ingredient. Prebiotics are indigestible food ingredients that exert a beneficial effect on the host and improve the host's health by selectively altering the proliferation and activity of specific bacteria in the large intestine. In the composition, one or more prebiotics may be used as the prebiotics in addition to the active ingredient.

[0174] There are no particular restrictions on prebiotics other than the active ingredient, as long as they do not interfere with the effect of the active ingredient contained in the composition. Examples of prebiotics other than the active ingredient include galactooligosaccharides, fructooligosaccharides (GF2, GF3, GF4), xylooligosaccharides, isomaltooligosaccharides, raffinose, lactulose, lactulose oligosaccharides, soybean oligosaccharides, caffeine oligosaccharides, dietary fiber, and gluconic acid.

[0175] Alternatively, the composition can also be used as a synbiotic, which, in addition to the active ingredient, may contain probiotics. A synbiotic is a combination of probiotics and prebiotics. Probiotics can be defined as microorganisms that provide beneficial effects to the host by being introduced into the host's gut in a live state.

[0176] There are no particular restrictions on probiotics as long as they do not interfere with the effectiveness of the active ingredients contained in the composition. Examples of probiotics include specific lactic acid bacteria.

[0177] In addition, the composition may further contain additives permitted as food or pharmaceutical products. Examples of such additives include 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, flavorings, acidulants, and natural products. More specifically, it includes water, other aqueous solvents, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymers, sodium alginate, dextrin, water-soluble dextran, water-soluble dextrin, corn starch, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petrolatum, paraffin wax, stearyl alcohol, stearic acid, magnesium stearate, precipitated calcium carbonate, talc, human serum albumin, mannitol, sorbitol, lactose, sucralose, lactose hydrate, maltose powder, white sugar, stevia, aspartame, acesulfame potassium, citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, vegetable juice, etc.

[0178] (Dosage form / form)

[0179] In one embodiment, the food composition can be prepared in any form, such as solid, liquid, mixture, suspension, powder, granules, paste, jelly, gel, capsule, etc. Furthermore, the food composition of the present invention can be formulated into dairy products, nutritional supplements (e.g., tablets, coated tablets, sugar-coated tablets, enteric coatings, etc.), capsules (enteric-coated soft capsules, enteric-coated hard capsules, colon-delivered capsules, etc.), snacks, beverages, drinks, seasonings, processed foods, home-cooked dishes, soups, etc. More specifically, the composition of the present invention can be formulated into liquid foods, semi-liquid foods, jellies, gels, powders, formula milk powder, formula liquid milk, milk powder / liquid milk for pregnant and lactating women, fermented milk, sticks, mousse, chocolate, biscuits, ice cream, fermented milk, lactic acid bacteria beverages, milk beverages, dairy beverages, soft drinks, fruit juice beverages, tablets, cheese, bread, biscuits, crackers, pizza, patient food, nutritional food, frozen food, and processed food. In addition, it can be formulated into granules, powders, pastes, thick liquids, etc., for mixing into beverages and foods. Granules and powders can be made into cubes or sticks (packaged into single-use portions). Regarding this invention, formula milk powder refers to powdered milk as defined in the "Ministry Ordinance Concerning Standards for the Composition of Milk and Dairy Products" (hereinafter referred to as the "Milk Ordinance"), which is made by processing raw milk, cow's milk, special cow's milk, or raw buffalo milk, or foods made from them, or by adding nutrients required by infants to it as a main ingredient. Regarding this invention, formula liquid milk refers to liquid milk as defined in the Milk Ordinance, which is made by processing raw milk, cow's milk, special cow's milk, or raw buffalo milk, or foods made from them, or by adding nutrients required by infants to it as a main ingredient.

[0180] In one manner, the pharmaceutical composition can be formulated into any dosage form suitable for oral administration, such as tablets, granules, powders, pills, capsules, etc., liquid preparations, suspensions, syrups, gels, aerosols, etc.

[0181] (Manufacturing methods, etc.)

[0182] In one approach, the compounding stage of the active ingredient in the manufacture of the composition can be appropriately selected. There are no particular limitations on the compounding stage, as long as it does not significantly impair the properties of the active ingredient. For example, the active ingredient can be compounded into the raw materials. Alternatively, the active ingredient can be added in the final stage of manufacturing to produce a composition containing the active ingredient.

[0183] (Mark)

[0184] In one approach, the intended use (purpose) may be indicated in the composition; in another approach, the function of the composition or active ingredient and the method of use based on the function may be indicated. Examples of methods of use based on the indicated function are as described above in the section on function / effect / effect. Additionally, in the compositions of the present invention, it may be indicated that they can be used as prebiotics or as synbiotics (a combination of probiotics and prebiotics). It should be noted that time periods such as "temporary" or "long-term" may also be appropriately indicated at the beginning of each statement.

[0185] In another approach, the composition is indicated as being recommended for a specific object. Examples of such objects are as described above.

[0186] Labeling can be explicit or implicit. Explicit labeling is the direct description of tangible objects such as the product itself, packaging, containers, labels, and signs. Implicit labeling (also known as tacit labeling) includes advertising / promotional activities based on location or means, such as websites, stores, brochures, exhibitions, media seminars, books, newspapers, magazines, television, radio, mail, emails, and audio.

[0187] In one approach, the recommended intake of the composition is labeled on an individual basis. This labeling can be done using the individual's documents (whether written or electronic), tablets, smartphones, personal computers, social media, etc. Furthermore, this labeling can be combined with the display of results from any examination or analysis, such as gut microbiota testing, fecal analysis, and fecal metabolomics analysis. It can also be effectively utilized in precision nutrition (which refers to recommending appropriate diets based on individualized nutrition and physical conditions).

[0188] [Apparatus, method of provision, etc.]

[0189] In this embodiment, a food information providing device is provided, comprising the following:

[0190] The information acquisition department acquires information about the gut microbiota of the subjects;

[0191] The export section, based on information about the gut microbiota, exports information about the food provided to the recipient; and

[0192] The department provides the exported food information to the recipients.

[0193] In a preferred embodiment, the information acquisition unit of the device acquires information on the presence or quantity of butyric acid bacteria from information on intestinal flora, and the output unit, based on the information on the presence or quantity of butyric acid bacteria, outputs information about a food, wherein the food is a composition containing any one of kojibiose and oligosaccharides with kojibiose as a constituent sugar.

[0194] In one approach, one can obtain any of the following information related to the object while obtaining information about the object's gut microbiota.

[0195] • Includes attribute information for any individual selected from groups consisting of the object's gender and age;

[0196] • Examination results related to the subject's physical / health status, which include any one of the following groups: height, weight, body mass index (BMI), obesity, body fat, waist circumference, blood pressure, lipids, liver / pancreatic function, metabolic system, blood, urine, kidney function, and large intestine.

[0197] • Survey results on the subjects' hobbies / lifestyle habits, including any one of the groups selected from dietary habits (hobbies), drinking habits, smoking habits, smoking history, exercise habits, and sleep duration; and

[0198] • Subject's subjective symptoms, stress, current / under-observational illnesses, medications / health supplements, medical history, and experience with pregnancy / childbirth; and

[0199] • Regarding the client's business background, overall life, and other information.

[0200] Information can also be obtained based on the responses to predetermined questions received from the respondents (e.g., responses to a questionnaire).

[0201] In one embodiment, the food information providing device is capable of displaying the provided food information on the user's terminal. In another embodiment, the device further includes a display unit for displaying the provided food information. The display unit can be the user's terminal, such as a tablet computer, smartphone, or personal computer.

[0202] In one embodiment, the food information providing device may include an analysis unit for analyzing bacterial flora, examining substances in feces, butyrate levels, and analyzing fecal metabolomics in samples obtained from the subject; and may also include an order receiving unit for accepting food orders from the subject based on the provided food information.

[0203] In this embodiment, a method for providing food information including the following steps is also provided:

[0204] Obtain information about the object's gut microbiota;

[0205] Based on gut microbiota information, information about the food provided to the recipient is derived; then...

[0206] Provide the exported food information to the object.

[0207] In a preferred embodiment, in the step of acquiring information, information on the presence or quantity of butyric acid bacteria is acquired from information on the gut microbiota; in the step of deriving food information, information on the food is derived based on the information on the presence or quantity of butyric acid bacteria, wherein the food is a composition comprising any one of kojibiose and oligosaccharides with kojibiose as a constituent sugar.

[0208] Such a method may also include the step of displaying the provided food information on the target's terminal. The target terminal may be, for example, a tablet, a smartphone, or a personal computer.

[0209] This embodiment also provides a method for controlling *Faecalibacterium* bacteria in the gut of a subject, or a method for supporting the subject's diet or health. This method implements the above-described method for providing food information, and further implements the following steps:

[0210] Methods for controlling the presence of *Femtobacter* bacteria in the gut of a subject, or methods for supporting the subject's dietary lifestyle or health, including a process of providing food to the subject based on derived food information.

[0211] In this embodiment, the term "food" is preferably used as a prebiotic or synbiotic. The term "food" may also be referred to as a food composition, and the description in the above-mentioned composition section applies directly.

[0212] [Cultivation methods, etc.]

[0213] As another embodiment, a method is provided for culturing butyric acid bacteria, preferably *Bacillus* spp., using any of the oligosaccharides selected from kohlbiose and those with kohlbiose as a constituent sugar; or, the use of any of the oligosaccharides selected from kohlbiose and those with kohlbiose as a constituent sugar in the culture of butyric acid bacteria, preferably *Bacillus* spp. The culture or use can also be carried out in the gut microbiota. As another embodiment, a method is provided for controlling the proliferation of *Bacillus* spp. in the gut microbiota, comprising the step of including the gut microbiota containing *Bacillus* spp. in the form of oligosaccharides selected from kohlbiose and those with kohlbiose as a constituent sugar. The above steps can be achieved by adding, supplying, fortifying, or supplementing the target component, etc.

[0214] The present invention will be further described in detail below using examples. However, the scope of the present invention is not limited to these examples.

[0215] Example

[0216] [Cultivation Example 1]

[0217] (Stool culture)

[0218] Compared to a fecal dilution containing feces from healthy adults suspended in Nissui (Nissui Pharmaceutical Co., Ltd.) semi-fluid medium for GAM sugar decomposition after filtration to remove agar, galactosyl kilobitose was added to achieve a concentration of 0.25% (n=60).

[0219] Sixty fecal samples were rapidly aliquoted under refrigeration after excretion and frozen at -80°C until use. These fecal samples were tested separately without mixing. It should be noted that the culture medium used in the experiments was allowed to stand in an anaerobic glove box for at least one night before use. Cultures were performed using 96-well deep-well plates at 37°C under anaerobic conditions for one day. The prebiotic activity of the added evaluation substance was evaluated by comparing the cultured bacterial population with a control condition where distilled water was added instead of galactosyl kosbiose.

[0220] (sample)

[0221] The galactosyl trebbiose (α-D-Glcp-(1→2)-[β-D-Galp-(1→4)-]D-Glcp) is a trisaccharide fraction containing galactosyl trebbiose as the main component, prepared in Manufacturing Example 1.

[0222] (Analysis of gut bacteria occupancy using next-generation sequencers)

[0223] DNA was extracted and purified from the cultured fecal dilution using the Maxwell RSC PureFood GMO & Authentication Kit (Promega), and amplicon sequencing of the V3-V4 region was performed using MiSeq (Illumina). The occupancy rate of each gut bacteria was calculated by analyzing the obtained .fastq files using QIIME2 (https: / / qiime2.org / ).

[0224] The presence of *Bacillus* spp. was significantly increased upon the addition of galactosyl trefoil. Figure 1 Wilcoxon signed-rank test, p=4.51×10 -7 ).

[0225] [Manufacturing Example 1]

[0226] (Preparation of enzyme solution)

[0227] Lactobacillus satsumensis JCM12392 was cultured overnight at 30°C using commercially available MRS liquid medium, and then cooled to below 10°C to end the culture. JCM12392 can be obtained from the Microbial Materials Development Laboratory, RIKEN BRC JCM (Tsukuba City, Ibaraki Prefecture, Japan).

[0228] The obtained culture medium was centrifuged, and the supernatant was discarded. The bacteria were then collected, and an equal volume of citrate-phosphate buffer (pH 5.0) was added to collect the bacteria again, thus washing the cells. The obtained cells were then resuspended by adding half the original volume of the above buffer to the culture medium, and this was used as the enzyme solution.

[0229] (Enzyme reaction)

[0230] A mixture of 32% sucrose, 16% lactose, and 10% enzyme solution was reacted at 48°C under static conditions for 18 hours. The composition contains, relative to the solid components, 25-30% galactosyl disaccharide, 15-20% lactose, and 30-35% fructose.

[0231] (Purification of galactosyltrimoniose)

[0232] The enzyme reaction solution was passed through a carbon diatomaceous earth column, followed by distilled water to remove non-adsorbed substances. Elution was then performed in stages using ethanol-water solutions of varying concentrations to obtain a trisaccharide fraction containing galactosyltrimoniose as the main component. Figure 2 ).

[0233] [Supplementary Example 1]

[0234] The inventors have confirmed to date that kojibiose and oligosaccharides with kojibiose as a constituent sugar promote the proliferation of *Parabacterium* bacteria (PCT / JP2023 / 030455, WO2024 / 043298). Furthermore, they have obtained the inspiration that by promoting the proliferation of *Parabacterium* bacteria, the proliferation of *Bacillus faecalis* can be controlled (Japanese Application No. 2024-042874).

[0235] *Pseudomonas dilataniae* JCM5825T and *Pseudomonas faecalis* JCM9497T were cultured in GAM semi-fluid medium filtered through a filter. The cultures were then centrifuged, and the supernatant was sterilized to remove bacterial cells. 1% of *F. preibryophyte* NCIMB13872T, *F. kanamycin*, *F. longimycin*, *F. garibrio*, and *F. butyrate-producing*, activated with MRC medium, was added to the sterilized culture medium, and the cultures were cultured anaerobicly for 24 hours. Turbidity was measured to evaluate the growth of these *F. preibryophyte* bacteria. Strains listed as NCIMB were obtained from the National Collection of Industrial and Marine Bacteria (NCIMB), UK. Strains listed as JCM were obtained from the Microbial Materials Development Laboratory, RIKEN BRC JCM (Tsukuba City, Ibaraki Prefecture, Japan).

[0236] The results showed that, compared with the control, the growth of *P. merdae* bacteria was promoted in the culture supernatants of *P. distasonis* and *P. merdae*. Figure 3 and 4 ).

[0237] Therefore, it can be said that the proliferation control of *Femtobacter* bacteria based on kohlbiose and oligosaccharides with kohlbiose as a constituent sugar may be achieved through the proliferation of *Parabacterium* bacteria. Based on the above, any oligosaccharide possessing the proliferation ability of *Parabacterium* bacteria can also possess the proliferation-promoting ability of *Femtobacter* bacteria.

[0238] [summary]

[0239] As shown above, galactosyl kohlbiose can be used to control the proliferation of *Faecalibacterium* bacteria in the gut. *Faecalibacterium* is a known butyric acid-producing bacterium in the gut. Therefore, it can be said that kohlbiose and oligosaccharides with kohlbiose as a constituent sugar can be used to control the proliferation of butyric acid bacteria, or to control butyric acid production in the gut, and thus to treat diseases or conditions that can be improved by controlling the proliferation of butyric acid bacteria.

[0240] Furthermore, reports have indicated a reduction in *Faecalibacterium* bacteria in the gut of patients with inflammatory bowel disease, including Crohn's disease and ulcerative colitis (Non-Patent Literature 1, etc.); similar reports have been made in patients with asthma, food allergies, non-alcoholic fatty liver disease, and chronic kidney disease (Non-Patent Literature 2-6, respectively); furthermore, compared to healthy individuals, *Faecalibacterium* bacteria were reduced in the gut of patients with irritable bowel syndrome (IBS) (Non-Patent Literature 7), inflammatory bowel disease (IBD) (Non-Patent Literature 8), Parkinson's disease (Non-Patent Literature 9), and cancer (Non-Patent Literature 10); administration of this genus of bacteria to IBD model mice improved symptoms such as weight loss and diarrhea (Non-Patent Literature 11); and administration of this genus of bacteria to Alzheimer's disease model mice improved cognitive impairment (Non-Patent Literature 12). Additionally, *Faecalibacterium prausnitzii* was reported to exhibit anti-inflammatory effects in cultured cell lines and TNBS colitis model mice (Non-Patent Literature 13). Therefore, it can be said that kojibiose and oligosaccharides with kojibiose as their constituent sugar can be used to treat these diseases or conditions. Furthermore, it can be said that consuming a combination of kojibiose and oligosaccharides with kojibiose as their constituent sugar as food is beneficial for supporting the individual's dietary lifestyle and improving health.

[0241] [Food Manufacturing Example 1: 100% Orange Juice Beverage]

[0242] 168g of 1 / 6 concentrated orange juice, 20g of the oligosaccharide composition (60% solids) obtained in Manufacturing Example 1, and a suitable amount of flavoring were dissolved in deionized water to make a total volume of 1000ml. This was filled into a container and sterilized at 65°C for 10 minutes to obtain a 100% orange juice beverage containing a trisaccharide fraction with galactosyl keratobiose as the main component. This juice beverage contains approximately 0.36-0.42g / 100g of galactosyl keratobiose. This juice beverage can be used to control the proliferation of *Bacillus flavus* bacteria.

[0243] [Food Manufacturing Example 2: Yogurt Beverage]

[0244] The raw materials—cream, skim milk concentrate, and water—are mixed and dissolved. The mixture is then heated to 110°C for 30 seconds to sterilize. After cooling to 43°C, a lactic acid bacteria starter culture composed of *Lactobacillus bulgaricus* and *Streptococcus thermophilus* is added, and the mixture is fermented until the acidity reaches 0.75. The homogenized solution is then mixed and dissolved with water, pectin, sucralose, a trisaccharide fraction containing galactosyl-glucan as the main component, and flavoring. This mixture is then heated to 80°C for 10 minutes to sterilize. The resulting solution is then cooled, mixed, and stirred before use. The mixing ratios of the raw materials are shown in the table below. The resulting yogurt beverage can be used for anti-obesity purposes.

[0245] [Table 1]

[0246]

[0247] [Food Manufacturing Example 3: Fermented Milk 1]

[0248] Raw milk was prepared by mixing 500.0g of raw milk, 53.2g of skim milk powder, 23.0g of fresh cream, 403.6g of tap water, and 50g of sucrose. The raw milk was sterilized by heating at 95℃ and then cooled. Next, 0.5% concentrated *Liquorilactobacillus satsumensis* was inoculated into the raw milk, and fermented at 48℃ under static conditions for 18 hours. Then, *Lactobacillus delbrueckii* subsp. bulgaricus and *Streptococcus thermophilus* were added as lactic acid bacteria starter cultures. The amount of starter cultures added was 20g. The raw milk containing the starter cultures was filled into 100ml plastic containers. The containers were then fermented in a fermentation chamber at 43℃ until the lactic acid concentration reached 0.7%. The resulting fermented milk can be used for immune control.

[0249] [Food Manufacturing Example 4: Fermented Milk 2]

[0250] Raw milk was prepared by mixing 500.0g of raw milk, 53.2g of skim milk powder, 23.0g of fresh cream, 403.6g of tap water, and 54g of trisaccharide fraction containing galactosyl disaccharide as the main component. The raw milk was then sterilized at 95°C and cooled to 43°C. Next, 20g of *Lactobacillus delbrueckii* subsp. bulgaricus and *Streptococcus thermophilus* were added as lactic acid bacteria starter cultures to the sterilized raw milk. The raw milk containing the starter cultures was then filled into 100ml plastic containers. The containers were then fermented in a 43°C fermentation chamber until the lactic acid content reached 0.7%. The resulting fermented milk can be used to improve liver function.

[0251] [Food Manufacturing Example 5: Syrup]

[0252] In the enzyme reaction conditions shown in Example 1, 20 w / w% whey powder (Meiji Co., Ltd.) (containing 75% lactose) was mixed in to replace lactose, and the enzyme reaction was carried out under the same conditions. After the reaction, the mixture was sterilized at 100°C. A sugar solution (syrup) showing the same chromatogram as in Example 1 was obtained. The obtained syrup can be used to promote butyrate production in the intestine.

[0253] Industrial availability

[0254] This invention supports the maintenance / improvement of human health through compositions for controlling the proliferation of butyric acid bacteria, wherein the aforementioned compositions comprise any of the group consisting of kojibiose and oligosaccharides with kojibiose as a constituent sugar. Furthermore, according to this invention, food compositions and methods for manufacturing foods that support the maintenance / improvement of human health are available. Moreover, according to this invention, various improvements in human nutrition can be achieved, ensuring a healthy life and promoting welfare.

Claims

1. A composition for controlling the proliferation of butyric acid bacteria, comprising any one selected from kojibiose and oligosaccharides with kojibiose as a constituent sugar.

2. The composition according to claim 1, wherein, Butyric acid bacteria belong to the genus Faecalibacterium.

3. The composition according to claim 1, which is used as a prebiotic or synbiotic.

4. A composition for treating any of the following conditions: inflammation, asthma, food allergy, non-alcoholic fatty liver disease, chronic kidney disease, dementia, irritable bowel syndrome, inflammatory bowel disease, Parkinson's disease, cancer, cognitive impairment, and atopic dermatitis, said composition comprising any of the following: kosperidin and oligosaccharides with kosperidin as a constituent sugar.

5. The composition according to claim 4, wherein, The treatment is carried out by controlling the proliferation of Bacillus faecalis bacteria in the gut.

6. A composition for controlling butyrate production in the intestine, comprising any one selected from kosperidin and oligosaccharides with kosperidin as a constituent sugar.

7. The composition according to claim 6, wherein, Butyrate production is controlled by controlling the proliferation of Bacillus faecalis bacteria in the gut.

8. A composition for treating a disease or condition that can be improved by controlling the proliferation of *Bacillus foetida* bacteria in the gut, said composition comprising kohlbiose and an oligosaccharide with kohlbiose as the constituent sugar.

9. The composition according to any one of claims 1 to 8, wherein, The composition is obtained by acting a raw material composition containing lactose and sucrose with dextran sucrase.

10. The composition according to any one of claims 1 to 3, 5, 7 and 8, wherein, Controlling proliferation is to promote proliferation.

11. The composition according to any one of claims 1 to 3, 5, 7 and 8, wherein, Butyric acid bacteria or bacteria of the genus Faecalibacterium are Faecalibacterium prausnitzii.

12. The composition according to claim 6 or 7, wherein, Controlling butyric acid production is to promote butyric acid production.

13. The composition according to any one of claims 1 to 8, wherein, The composition contains a substance capable of promoting the proliferation of Parabacteroides as any one selected from kosperidone and oligosaccharides with kosperidone as a constituent sugar.

14. The composition according to any one of claims 1 to 8, wherein, The composition contains galactosyl kosbiose as any one selected from kosbiose and oligosaccharides with kosbiose as the constituent sugar.

15. A method for providing food information, comprising the following steps: Obtain information about the object's gut microbiota; Based on gut microbiota information, information about the food provided to the recipient is derived. Then Provide the exported food information to the object. In the information acquisition process, information on the presence or quantity of *Bacillus* spp. is obtained from the gut microbiota information. In the food information derivation process, food information is derived based on the presence or quantity of *Bacillus* spp., wherein the food is a composition comprising any one of the groups selected from kohlbiose and oligosaccharides with kohlbiose as the constituent sugar.

16. A method for providing food information, comprising the following steps: Obtain information about the amount of butyrate in the object's intestines; Based on information about intestinal butyrate levels, information about the food provided to the recipients is derived; then... Provide the exported food information to the object. In the process of deriving information about a food, information about the food is derived based on information about the amount of butyrate in the intestine, wherein the food is a composition comprising any one of the groups selected from kosperidin and oligosaccharides with kosperidin as a constituent sugar.

17. A method for controlling the presence of *Faecalibacterium* bacteria in the gut of an individual, or a method for supporting the dietary lifestyle or health of an individual, comprising the method of claim 15 or 16, and including the step of providing food to the individual based on derived food information.

18. The method according to claim 15 or 16, wherein, Foods are used as prebiotics or synbiotics.

19. The method of claim 16, further comprising the step of displaying the provided food information on the terminal of the object.

20. Use for controlling the proliferation of *Bacillus* bacteria in the gut microbiota, using any of the following: kosperidose and oligosaccharides whose constituent sugar is kosperidose.

21. A method for controlling the proliferation of *Bacillus* spp. in the gut microbiota, comprising the step of containing the *Bacillus* spp. gut microbiota with any of the following: kosperidose and oligosaccharides with kosperidose as a constituent sugar.

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