Compositions for controlling the proliferation of bacteria of the genus fusobacterium

Abstract

The objective of this invention is to provide a means for controlling the proliferation of *Streptobacter* spp. A composition for controlling the proliferation of *Streptobacter* spp. is provided, 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 bacteria of the genus *Fusicatenibacter*. Background Technology

[0002] *Streptomyces* spp. are bacteria found in the human gut microbiota. Non-patent literature 1 reports a significantly lower prevalence of *Streptomyces sucrose* in patients with ulcerative colitis compared to healthy individuals. Furthermore, this literature suggests that administering heat-sterilized *Streptomyces sucrose* to a mouse model of oxazolone-induced colitis inhibited inflammation, revealing a mechanism mediated by the inhibition of IL-10 and IL-13 production, which is increased by oxazolone. Non-patent literature 2 reports that Parkinson's disease symptoms are predicted to progress in patient groups with lower *Streptomyces* spp. populations; however, this reduction in bacterial count is not a result of symptom progression. Furthermore, according to non-patent literature 3, *Streptomyces* spp. are distributed at a high frequency / number in adults, while their frequency and number are low in the elderly, approximately one-tenth of that in adults.

[0003] Regarding *Streptobacter fusiformis* bacteria, Patent Document 1 discloses a composition containing indigestible dextrin as an active ingredient for promoting the proliferation of *Streptobacter fusiformis* bacteria. Furthermore, Patent Document 2 discloses a composition for treatment containing live strains of *Streptobacter fusiformis*, and describes a method for using this composition to treat or prevent diseases or disorders selected from the group consisting of diseases, disorders or states of the central nervous system, intestinal barrier dysfunction, diseases related to increased intestinal permeability, inflammatory diseases, metabolic diseases, and cardiovascular diseases.

[0004] On the other hand, kojibiose is known to promote the proliferation of Bifidobacteria (e.g., Non-Patent Document 4). Furthermore, Patent Document 3 describes an in vivo lipid regulator containing one or more of kojibiose, kojitriose, kojibiose glucoside, kojitetraose, and kojitriose glucoside as active ingredients. Additionally, Patent Document 4 describes a dosage form containing a composition with microbial control factors; sugars or sugar alcohols are examples of ingredients that may be included in the formulation, and kojibiose is described as an example. The formulation is also described for treating individuals with dysbiosis, such as inflammatory bowel disease. Furthermore, Patent Document 5 describes a method for treating a subject with a disease or disorder associated with metabolites that are not at desired levels. This method includes: selecting a polysaccharide polymer preparation based on regulating the production or level of the metabolites through arbitrary selection; and administering an effective amount of the polysaccharide polymer preparation for regulating the level of the metabolites, thereby treating the disease or disorder. Examples of diseases described include Crohn's disease, Parkinson's disease, and ulcerative colitis. Additionally, this document describes polysaccharide polymers containing α-1,2-glycosidic bonds, and trichomoniasis is described as an example of a starting material for polysaccharide structural units.

[0005] Existing technical documents

[0006] Patent documents

[0007] Patent Document 1: Japanese Patent Application Publication No. 2020-83830 (Japanese Patent No. 7164869)

[0008] Patent Document 2: WO021 / 098991 (Japanese Patent Publication No. 2023-503410)

[0009] Patent Document 3: Japanese Patent Application Publication No. 2005-281188 (Japanese Patent No. 4746281)

[0010] Patent Document 4: WO2016 / 172658 (Japanese Patent Publication No. 2018-513196)

[0011] Patent Document 5: WO2018 / 106845 (Japanese Patent Publication No. 2020-513410)

[0012] Non-patent literature

[0013] Non-patent literature 1: Inflamm Bowel Dis. 2016 Dec;22(12):2802-2810.

[0014] Non-patent literature 2: NPJ Parkinsons Dis. 2022 Jun 1;8(1):65.

[0015] Non-patent literature 3: PLoS One. 2015 May 22;10(5):e0126226.

[0016] Non-patent literature 4: Journal of agricultural and food chemistry. 2005, 53, 5192-5199. Summary of the Invention

[0017] The problem the invention aims to solve

[0018] Given the numerous reports demonstrating the close relationship between gut bacteria and health, it is possible to reduce the risk of various diseases by controlling the proliferation of these important bacteria. In particular, it is believed that inhibiting the decline of Streptomyces fusiforme bacteria associated with aging through prebiotic intake is effective in reducing disease risk.

[0019] By utilizing prebiotics to control the proliferation of Streptomyces fusiforme bacteria in the gut, it is expected that various diseases can be prevented and improved.

[0020] Solution for solving the problem

[0021] This invention provides the following content.

[0022] [1] A composition for controlling the proliferation of bacteria of the genus *Fusicatenibacter*, comprising any one of kosperidin and oligosaccharides whose constituent sugar is kosperidin.

[0023] [2] The composition according to 1 is used as a prebiotic or synbiotic.

[0024] [3] A composition for treating any of the following: inflammatory bowel disease and Parkinson's disease, comprising any of the following: kosperidin and oligosaccharides with kosperidin as the constituent sugar.

[0025] [4] The composition according to 3, wherein the treatment is carried out by means of controlling the proliferation of Streptomyces spp. in the intestine.

[0026] [5] A composition for treating a disease or condition that can be improved by controlling the proliferation of Streptomyces fusiforme bacteria in the gut, the composition comprising kohlbiose and an oligosaccharide with kohlbiose as the constituent sugar.

[0027] [6] The composition according to any one of 1 to 5, wherein the composition is obtained by acting a dextran sucrase on a raw material composition comprising lactose and sucrose.

[0028] [7] The composition according to any one of 1, 2 and 4 to 6, wherein controlling proliferation is promoting proliferation.

[0029] [8] The composition according to any one of 1 to 7, wherein the composition comprises galactosyl kosbiose as any one selected from kosbiose and oligosaccharides with kosbiose as the constituent sugar.

[0030] [9] A method for providing food information, comprising the following steps:

[0031] Obtain information about the object's gut microbiota;

[0032] Based on gut microbiota information, information about the food provided to the recipient is derived; then...

[0033] Provide the exported food information to the object.

[0034] In the information acquisition process, information on the presence or quantity of Streptomyces fusiforme bacteria is obtained from the gut microbiota information. In the food information derivation process, based on the information on the presence or quantity of Streptomyces fusiforme bacteria, the food information is derived, wherein the food is a composition comprising any one of the groups selected from kosmobiose and oligosaccharides with kosmobiose as the constituent sugar.

[0035]

[10] A method for controlling Streptomyces fusiformis bacteria in the gut of a subject, or a method for supporting the subject’s diet or health, comprising the method described in embodiment 9, and including the step of providing food to the subject based on derived food information.

[0036]

[11] The method according to 9 or 10, wherein the food is used as a prebiotic or synbiotic.

[0037]

[12] The method according to any one of 9 to 11 further includes the step of displaying the provided food information on the terminal of the object.

[0038]

[13] Use for controlling the proliferation of Streptomyces fusiforme in the gut microbiota, selected from any of kosbiose and oligosaccharides with kosbiose as the constituent sugar.

[0039]

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

[0040]

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

[0041]

[23] A composition for use in a method of treating any of inflammatory bowel disease and Parkinson's disease, the composition comprising any of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar. Use of any of the group consisting of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar in the manufacture of a composition for treating any of inflammatory bowel disease and Parkinson's disease. A method or non-therapeutic method for treating any of inflammatory bowel disease and Parkinson's disease, comprising the step of administering a composition to a subject, the composition comprising any of the group consisting of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar. Use or non-therapeutic use of a composition comprising any of the group consisting of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar for treating any of inflammatory bowel disease and Parkinson's disease.

[0042]

[24] The composition, use in manufacture, method or non-therapeutic use, or use or non-therapeutic use according to 23, wherein the treatment is carried out by means of controlling the proliferation of Streptomyces spp.

[0043]

[25] A composition comprising any one of thymolinosaccharides selected from the group consisting of thymolinosaccharides and oligosaccharides whose constituent sugars are thymolinosaccharides, for use in a method of treating a disease or condition that can be improved by controlling the proliferation of *Streptobacter* spp. in the gut. Use of any one of thymolinosaccharides selected from the group consisting of thymolinosaccharides and oligosaccharides whose constituent sugars are thymolinosaccharides, in the manufacture of a composition for treating a disease or condition that can be improved by controlling the proliferation of *Streptobacter* spp. in the gut. A method or non-therapeutic method for treating a disease or condition that can be improved by controlling the proliferation of *Streptobacter* spp. in the gut, comprising the step of administering to a subject a composition comprising any one of the group consisting of thymolinosaccharides selected from the group consisting of oligosaccharides whose constituent sugars are thymolinosaccharides. Use or non-therapeutic use of a composition comprising any one of the group consisting of thymolinosaccharides selected from the group consisting of oligosaccharides whose constituent sugars are thymolinosaccharides, for treating a disease or condition that can be improved by controlling the proliferation of *Streptobacter* spp. in the gut.

[0044]

[26] The composition, use in manufacture, method or non-therapeutic use, or use or non-therapeutic use according to any one of 21 to 25, wherein the composition is obtained by acting a dextran sucrase on a raw material composition comprising lactose and sucrose.

[0045]

[27] The composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use according to any one of 21, 22, 24 to 26, wherein controlling proliferation is promoting proliferation.

[0046]

[28] The composition, use in manufacture, method or non-therapeutic use, or use or non-therapeutic use according to any one of 21 to 27, wherein the composition comprises galactosyl kosbiose as any one selected from kosbiose and oligosaccharides with kosbiose as the constituent sugar.

[0047]

[29] A method for controlling the proliferation of Streptomyces spp. in the gut microbiota, comprising the step of making the gut microbiota containing Streptomyces spp. contain any of the oligosaccharides selected from kohlbiose and oligosaccharides with kohlbiose as the constituent sugar.

[0048] The effects of the invention

[0049] By using any of the oligosaccharides selected from kohlbiose and kohlbiose as constituent sugars as prebiotics, it is possible to increase *Streptomyces fusiforme* bacteria in the gut. Furthermore, by increasing *Streptomyces fusiforme* bacteria in the gut, the prevention and improvement of various diseases can be expected. Attached Figure Description

[0050] [ Figure 1[Changes in the occupancy of *Streptococcus fusiforme* 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.]

[0051] [ Figure 2 Chromatograms of the enzyme reaction solution and the trisaccharide and tetrasaccharide fractions after fractionation and purification. Detailed Implementation

[0052] This embodiment relates to a composition for controlling the proliferation of bacteria of the genus *Streptococcus*, represented by *Streptococcus fusiformis*, using kojibiose and oligosaccharides with kojibiose as the constituent sugar as active ingredients.

[0053] [Active Ingredients]

[0054] 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)).

[0055] 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.

[0056] 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.

[0057] 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.

[0058] 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.

[0059]

[0060] 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.

[0061] 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.

[0062] According to the research of the inventors, galactosyltrimonibiose has been confirmed to have excellent effects in controlling the proliferation of *Streptomyces fusiformis*, a type of *Streptomyces*. Here, galactosyltrimonibiose is an oligosaccharide containing trimonibiose 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 trimonibiose. Therefore, if trimonibiose is used as a constituent sugar, trimonibiose is also produced in the intestine, and the same effect as galactosyltrimonibiose can be achieved.

[0063] 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).

[0064] 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.

[0065] 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*.

[0066] 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.

[0067] 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*.

[0068] 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.

[0069] 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.

[0070] 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.

[0071] [use]

[0072] (Function / Effect / Effect)

[0073] The composition of this embodiment can be used to control the proliferation of bacteria belonging to the genus *Streptobacter* (sometimes simply referred to as *Streptobacter* bacteria). In a preferred embodiment, the composition can be used to control the proliferation of *Streptobacter* bacteria in the human gut. Controlling the proliferation of *Streptobacter* bacteria in the human gut means controlling the proliferation of *Streptobacter* bacteria in the presence of various bacteria in the human gut (sometimes also referred to as gut microbiota). Regarding this invention, when referred to as gut microbiota, it means the community of various bacteria residing in the gut, including, for example, the bacteria contained in feces, but not limited to the microbiota located in the gut. Regarding this invention, control includes upward control (sometimes also referred to as promotion, increase) and downward control (sometimes also referred to as inhibition, decrease), preferably upward control. Proliferation control can be control of the bacterial count or control of the occupancy rate described later.

[0074] 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.

[0075] In a preferred embodiment, the composition is used to control the proliferation of bacteria belonging to the genus *Streptobacter* in the gut.

[0076] Bacteria belonging to the genus *Fusicatenibacter* include *Fusicatenibacter faecihominis* and *Fusicatenibacter saccharivorans*.

[0077] In this invention, when referring to bacteria of the genus *Streptobacter*, it means bacteria identified as belonging to the genus *Streptobacter* through molecular systematic analysis based on the 16S rRNA gene. The criteria for determining a 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).

[0078] 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.

[0079] Whether a component controls the proliferation of *Streptobacter fusiformis* bacteria in the gut can be evaluated as follows: Fecal samples containing *Streptobacter fusiformis* 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 *Streptobacter fusiformis* 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.

[0080] The number of *Streptomyces* 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. TMNext-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.

[0081] In one manner, the composition can be used to treat any of the diseases selected from inflammatory bowel disease and Parkinson's disease. Treatment is not limited to, except as specifically described, by means of controlling the proliferation of *Streptobacter* bacteria in the intestine.

[0082] *Streptomyces* spp. are bacteria discovered in the human gut microbiota. Regarding *Streptomyces sucrosei*, it has been reported that *Streptomyces sucrosei* is significantly less abundant in patients with ulcerative colitis compared to healthy individuals. Furthermore, administration of heat-sterilized *Streptomyces sucrosei* to a mouse model of oxazolone-induced colitis suppressed inflammation, and the mechanism is believed to be mediated by the inhibition of IL-10 and IL-13, the production of which is increased by oxazolone (Non-Patent Literature 1). Additionally, the progression of Parkinson's disease symptoms is predicted in patient populations with low *Streptomyces* spp. counts (Non-Patent Literature 2). Moreover, it has been reported that *Streptomyces* spp. are distributed at a high frequency / count in adults, while their frequency and count are low in the elderly (Non-Patent Literature 3). Therefore, in one manner, the composition can be used to treat any species selected from inflammatory bowel disease and Parkinson's disease, i.e., treatment that can be used by means of controlling the proliferation of Streptomyces spp. bacteria in the gut.

[0083] Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. Parkinson's disease includes early-onset Parkinson's disease with onset before age 40. Management of Parkinson's disease includes managing any symptoms. Symptoms of Parkinson's disease include: motor symptoms such as tremor, bradykinesia, rigidity (muscle stiffness), and postural instability; and non-motor symptoms such as constipation, urinary frequency, sweating, fatigue, decreased sense of smell, orthostatic hypotension, depressed mood, and apathy or lack of interest.

[0084] When used to treat inflammatory bowel disease, the composition may be formulated without any of the following:

[0085] 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.

[0086] In addition, the composition can be used to treat diseases or conditions that can be improved by controlling the proliferation of *Streptobacter* bacteria in the gut. Such diseases or conditions include a variety of diseases or conditions besides inflammatory bowel disease and Parkinson's disease.

[0087] Regarding the present invention, when discussing the management of a disease or condition, it includes reducing the risk of onset, delaying onset, 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-therapeutic 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. Furthermore, prevention or reduction of the risk of onset includes recommendations for the intake of specific foods and nutritional guidance (including guidance on nutrition required for the recovery of the injured and sick, and guidance on nutrition for maintaining and promoting health).

[0088] (object)

[0089] The composition of this embodiment is suitable for administration to: individuals who wish to or need to control the proliferation of *Streptobacter* bacteria in the gut; elderly individuals; individuals at risk of any of inflammatory bowel disease and Parkinson's disease; and individuals who wish to or need treatment for any of inflammatory bowel disease and Parkinson's disease. Elderly individuals are defined as those 65 years of age or older.

[0090] Subjects who wish to or need to control the proliferation of *Streptomyces fusiformis* in the gut include those in whom *Streptomyces fusiformis* is detected in small amounts in at least one of the gut or feces. Additionally, subjects who wish to or need to control the proliferation of *Streptomyces fusiformis* in the gut include: those considered to have a low number or prevalence of *Streptomyces fusiformis* in the gut based on any examination / analysis such as intestinal flora testing, fecal matter examination, and fecal metabolomics analysis; those considered to be at high risk from any species of inflammatory bowel disease and Parkinson's disease; and those recommended to consume foods, drinks, or medications to control the proliferation of *Streptomyces fusiformis* in the gut based on examination / analysis results and through the judgment of doctors, nurses, pharmacists, nutritionists, etc., or through computer programs.

[0091] Objects in which at least one of the intestines and feces is found to have a low number or occupancy of *Streptococcus fusiforme* bacteria include, for example, cases where, when a culture containing feces collected from the object is cultured at 37°C under anaerobic conditions for 24 hours, the occupancy of *Streptococcus fusiforme* bacteria in the culture is less than 4%, less than 3%, less than 2%, less than 1.5%, less than 1%, or less than 0.5%.

[0092] 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.

[0093] There is no particular age limit for the recipients, including, for example, newborns (within 28 days of age); infants (less than 1 year old); toddlers (1-6 years old); children (7 years and older but less than 15 years old); adults (15 years and older); and those 65 years and older. The composition of this embodiment is particularly suitable for administration to elderly people aged 65 and older.

[0094] [Composition]

[0095] (Food compositions, etc.)

[0096] 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 "Dietary supplement" 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.

[0097] (Provide assistance, etc.)

[0098] 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."

[0099] 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.

[0100] 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.

[0101] (Dosage, content)

[0102] 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.

[0103] 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.

[0104] 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.

[0105] 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.

[0106] (Other ingredients, additives)

[0107] 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.

[0108] 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.

[0109] 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.

[0110] 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.

[0111] 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.

[0112] 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.

[0113] (Dosage form / form)

[0114] 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 made 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 and Other Ministry 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 and Other Ministry 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.

[0115] 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.

[0116] (Manufacturing methods, etc.)

[0117] 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.

[0118] (Mark)

[0119] 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.

[0120] In another approach, the composition is indicated as being recommended for a specific object. Examples of such objects are as described above.

[0121] 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.

[0122] 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).

[0123] [Providing apparatus, providing methods, etc.]

[0124] In this embodiment, a food information providing device is provided, comprising the following:

[0125] The information acquisition department acquires information about the gut microbiota of the subjects;

[0126] The export section, based on information about the gut microbiota, exports information about the food provided to the recipient; and

[0127] The supply department provides the exported food information to the recipients.

[0128] In a preferred embodiment, the information acquisition unit of the device acquires information on the presence or quantity of Streptomyces fusiforme bacteria from the information on the intestinal flora, and the output unit, based on the information on the presence or quantity of Streptomyces fusiforme bacteria, outputs information about a food, wherein the food is a composition containing any one of kosbiose and oligosaccharides with kosbiose as the constituent sugar.

[0129] In one approach, one can obtain any of the following information related to the object while obtaining information about the object's gut microbiota.

[0130] • Includes attribute information for any individual selected from groups consisting of the object's gender and age;

[0131] • 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.

[0132] • 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

[0133] • Subject's subjective symptoms, stress, current / under-observational illnesses, medications / health supplements, medical history, and experience with pregnancy / childbirth; and

[0134] • Regarding the client's business background, overall life, and other information.

[0135] Information can also be obtained based on the responses to predetermined questions received from the respondents (e.g., responses to a questionnaire).

[0136] In one embodiment, the food information providing device is able to display information about the food being provided on the user's terminal. In another embodiment, the device further includes a display unit for displaying information about the food being provided. The display unit can be the user's terminal, such as a tablet computer, smartphone, or personal computer.

[0137] In one embodiment, the food information providing device may include an analysis unit for analyzing bacterial flora in samples obtained from a user, and may also include an order receiving unit for accepting food orders from a user based on the provided food information.

[0138] In this embodiment, a method for providing food information including the following steps is also provided:

[0139] Obtain information about the object's gut microbiota;

[0140] Based on gut microbiota information, information about the food provided to the recipient is derived; then...

[0141] Provide the exported food information to the object.

[0142] In a preferred embodiment, in the step of acquiring information, information on the presence or quantity of *Streptobacter* 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 *Streptobacter* bacteria, wherein the food is a composition comprising any one of kohlbiose and oligosaccharides with kohlbiose as a constituent sugar.

[0143] Such a method may also include the step of displaying information about the provided food on the recipient's terminal. The recipient's terminal could be, for example, a tablet, a smartphone, or a personal computer.

[0144] This embodiment also provides a method for controlling Streptomyces fusiforme 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 then implements the following steps:

[0145] Methods for controlling Streptomyces fusiformis 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.

[0146] 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.

[0147] [Cultivation methods, etc.]

[0148] As another embodiment, a method for culturing *Streptococcus fusiforme* bacteria using any of the oligosaccharides selected from kohlbiose and kohlbiose as constituent sugars is provided, or the use of any of the oligosaccharides selected from kohlbiose and kohlbiose as constituent sugars in the culture of *Streptococcus fusiforme* bacteria is provided. Cultivation or use can also be performed in the gut microbiota. As another embodiment, a method for controlling the proliferation of *Streptococcus fusiforme* bacteria in the gut microbiota is provided, comprising the step of including the gut microbiota containing *Streptococcus fusiforme* bacteria with any of the oligosaccharides selected from kohlbiose and kohlbiose as constituent sugars. The above steps can be achieved by adding, supplying, fortifying, supplementing target components, etc.

[0149] The present invention will be further described in detail below using examples. However, the technical scope of the present invention is not limited to these examples.

[0150] Example

[0151] [Cultivation Example 1]

[0152] (Stool culture)

[0153] A fecal dilution containing feces from healthy adults was prepared by adding galactosyl glibenclamide (α-D-Glcp-(1→2)-[β-D-Galp-(1→4)-]D-Glcp) to a concentration of 0.25% (n=60) to a semi-fluid medium for GAM sugar decomposition, "Nissui" (Nissui Pharmaceutical Co., Ltd.), in which agar was removed by filtration.

[0154] 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.

[0155] (sample)

[0156] 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.

[0157] (Analysis of gut bacteria occupancy using next-generation sequencers)

[0158] 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 / ).

[0159] A significant increase in the occupancy of *Streptobacter* spp. was observed upon the addition of galactosyltrimoniose. Figure 1 Wilcoxon signed-rank test, p=3.63x10 -9 ).

[0160] [Manufacturing Example 1]

[0161] (Preparation of enzyme solution)

[0162] Lactobacillus satsumensis JCM12392 was cultured overnight at 30°C using commercially available MRS liquid medium, then cooled to below 10°C to terminate the culture. Strain JCM12392 can be obtained from the Japan Collection of Microorganisms (RIKEN BRC-JCM, Japan) under the JCM number JCM12392 from the RIKEN Center for Biological Resources (RIKEN BRC-JCM, Japan).

[0163] 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.

[0164] (Enzyme reaction)

[0165] 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.

[0166] (Purification of galactosyltrimoniose)

[0167] 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 ).

[0168] [summary]

[0169] As shown above, galactosyl kohlbiose can be used to control the proliferation of *Streptobacter* spp. Furthermore, galactosyl kohlbiose may be converted into kohlbiose by lactase in the intestine. Therefore, it can be said that kohlbiose and oligosaccharides with kohlbiose as their constituent sugar can be used to control the proliferation of *Streptobacter* spp., and can also be used to treat diseases or conditions that can be improved by controlling the proliferation of *Streptobacter* spp.

[0170] Furthermore, *Streptobacter* spp. are bacteria found in the human gut microbiota. Regarding *Streptobacter* sucrose-eating, it has been reported that *Streptobacter* sucrose-eating is significantly less abundant in patients with ulcerative colitis compared to healthy individuals. Additionally, inflammation was suppressed by administering heat-sterilized *Streptobacter* sucrose-eating to oxazolone-induced colitis models in mice, and this mechanism is believed to be mediated by the inhibition of IL-10 and IL-13, the production of which is increased by oxazolone (Non-Patent Literature 1). Furthermore, Parkinson's disease symptoms are predicted to progress in patient populations with low *Streptobacter* spp. counts (Non-Patent Literature 2). Moreover, it has been reported that *Streptobacter* spp. are distributed at a high frequency / count in adults, while their frequency and count are low in the elderly (Non-Patent Literature 3). Therefore, it can be said that kohlbiose and oligosaccharides with kohlbiose as a constituent sugar can be used to treat these diseases or conditions. Furthermore, it can be said that consuming a combination of kojibiose and oligosaccharides composed of kojibiose as food is beneficial for supporting the dietary lifestyle and improving health. It is particularly suitable for elderly people aged 65 and over.

[0171] [Food Manufacturing Example 1: 100% Orange Juice Beverage]

[0172] 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 *Streptobacter* spp.

[0173] [Food Manufacturing Example 2: Yogurt Beverage]

[0174] The raw materials—cream, skim milk concentrate, and water—are mixed and dissolved, 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 fermentation is carried out 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, and the resulting solution is mixed and stirred after cooling before use. The mixing ratios of the raw materials are shown in the table below. The resulting yogurt beverage can be used for the treatment of lipid metabolism disorders.

[0175] [Table 1]

[0176]

[0177] [Food Manufacturing Example 3: Fermented Milk 1]

[0178] 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 raw milk in the containers was then allowed to ferment statically in a fermentation chamber at 43℃ until the lactic acid level reached 0.7%. The resulting fermented milk can be used for the treatment of lipid metabolism disorders.

[0179] [Food Manufacturing Example 4: Fermented Milk 2]

[0180] 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-glucobiose 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 for the treatment of diabetes.

[0181] Industrial availability

[0182] This invention supports the maintenance / improvement of human health through compositions for controlling the proliferation of *Streptobacter* spp., wherein the compositions comprise any of the group consisting of kohlbiose and oligosaccharides with kohlbiose 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 bacteria of the genus *Fusicatenibacter*, comprising any one selected from kosperidin and oligosaccharides with kosperidin as a constituent sugar.

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

3. A composition for treating any of the following: inflammatory bowel disease and Parkinson's disease, comprising any of the following: kosperidin and oligosaccharides with kosperidin as a constituent sugar.

4. The composition according to claim 3, wherein, The treatment is carried out by controlling the proliferation of Streptomyces fusiforme bacteria in the gut.

5. A composition for treating a disease or condition that can be improved by controlling the proliferation of Streptomyces spp. in the gut, said composition comprising kohlbiose and an oligosaccharide with kohlbiose as the constituent sugar.

6. The composition according to any one of claims 1 to 5, wherein, The composition is obtained by acting a raw material composition containing lactose and sucrose with dextran sucrase.

7. The composition according to any one of claims 1, 2, 4 and 5, wherein, Controlling proliferation is to promote proliferation.

8. The composition according to any one of claims 1 to 5, wherein, The composition contains galactosyl kosbiose as any one selected from kosbiose and oligosaccharides with kosbiose as the constituent sugar.

9. 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 Streptomyces fusiforme bacteria is obtained from the gut microbiota information. In the food information derivation process, based on the information on the presence or quantity of Streptomyces fusiforme bacteria, the food information is derived, wherein the food is a composition comprising any one of the groups selected from kosmobiose and oligosaccharides with kosmobiose as the constituent sugar.

10. A method for controlling Streptomyces fusiformis bacteria in the gut of a subject, or a method for supporting the subject's dietary lifestyle or health, comprising the method of claim 9, and including the step of providing food to the subject based on derived food information.

11. The method according to claim 9 or 10, wherein, Foods are used as prebiotics or synbiotics.

12. The method of claim 9, further comprising the step of displaying the provided food information on the terminal of the object.

13. Use for controlling the proliferation of Streptomyces fusiforme in the intestinal flora, of any of the following: kosmobiose and oligosaccharides whose constituent sugar is kosmobiose.

14. A method for controlling the proliferation of *Streptobacter* spp. in the gut microbiota, comprising the step of containing the gut microbiota containing *Streptobacter* spp. with any one of kosperidose and oligosaccharides with kosperidose as a constituent sugar.

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