Composition for controlling proliferation of bacteria belonging to genus parabacteroides

Abstract

Provided is a composition for controlling the proliferation of a bacterium belonging to the genus Parabacteroides. The present invention addresses the problem of increasing the occupancy of bacteria belonging to the genus parabacteroides and bacteria belonging to the genus bifidobacterium in the intestinal flora. Provided is a composition for improving intestinal flora, which contains any one selected from the group consisting of trehalose, isomaltulose, pinose and maltulose, and an oligosaccharide having any one of these as a constituent sugar.

Description

Technical Field

[0001] The present invention relates to a composition for controlling the growth of Parabacteroides bacteria. Background Art

[0002] In recent years, intestinal barrier dysfunction, known as leaky gut, caused by lifestyle habits and stress, has become a recognized problem. Because harmful substances can travel throughout the body through blood vessels, it has been suggested that inflammation caused by leaky gut is not limited to intestinal inflammation but is also linked to the onset and progression of lifestyle-related diseases such as obesity and diabetes. As one of the strategies to improve leaky gut, research is underway to improve the intestinal flora.

[0003] Parabacteroides is one of the bacteria that inhabit the intestine. Regarding Parabacteroides, for example, in non-patent literature 1, the possibility of preventing food-induced obesity and type 2 diabetes by regulating the composition of intestinal flora by separating fractions containing Hirsutella sinensis mycelium (HSM) and polysaccharides has been studied. The document reports that a specific fraction selectively promotes the proliferation of Parabacteroides goldsteinii, a resident bacterium whose level is reduced in mice fed a high-fat diet (HFD). In addition, when live P. goldsteinii is orally administered to mice fed an HFD, obesity is reduced and is associated with an increase in the heat production of adipose tissue, an improvement in intestinal health, and a reduction in the level of inflammation and insulin resistance. In addition, in non-patent document 2, the metabolic effects of Parabacteroides distasonis (PD) on the reduction of weight gain, hyperglycemia and fatty liver in HFD-fed mice were studied. The document reports that when P. distasonis was administered to HFD-fed mice, lithocholic acid and ursodeoxycholic acid increased, the bile acid profile showed dramatic changes, and intestinal succinate levels increased. Furthermore, non-patent document 3 reports that P. distasonis membrane fraction (PdMb) strongly inhibited the production of inflammatory cytokines in colon cancer cell lines, reduced the expression of MyD88 and pAkt (ser473) induced by Escherichia coli lipopolysaccharide, and furthermore, PdMb induced apoptosis in colon cancer cell lines and inhibited TLR4 activation in reporter cell lines. The paper points out that these results suggest that P. distasonis has anti-inflammatory and anti-cancer effects, which are believed to be induced by inhibiting TLR4 and Akt signaling and promoting cell apoptosis.

[0004] Furthermore, non-patent document 4 mentions a decrease in P. distasonis in patients with multiple sclerosis (MS), and non-patent document 5 reports the results of a multivariate analysis showing that a combination of bacteria from the genus Oscillospira, the genus Rickenellaceae, and the genus Parabacteroides can distinguish between patients with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRLs). In addition, non-patent document 6 reports that oral administration of Parabacteroides goldsteinii improved weight loss and the rise of inflammatory cytokines in lung tissue in mice with smoking-induced chronic obstructive pulmonary disease (COPD). In addition, the document suggests that, as a mechanism of action, pentaacyl lipopolysaccharide, a cell wall component of Parabacteroides goldsteinii, antagonizes the activation of TLR4 receptors caused by inflammatory hexaacyl lipopolysaccharides from intestinal bacteria.

[0005] On the other hand, it is known that trehalulose, isomaltulose, turanose and maltulose have some functions. For example, Patent Document 1 lists trehalulose, isomaltulose and the like as prebiotic ingredients for adjusting the intestinal bacterial environment. In addition, Patent Document 2 describes the use of a low-glycemic index food composition in the manufacture of functional foods for treating and / or preventing malignant tumor diseases in the human or animal body, wherein the food composition contains isomaltulose, leucrose, trehalulose and / or turanose alone or in combination with sugar alcohols, inulin, polydextrose and / or indigestible starch as a low-glycemic index carbohydrate supply source. Furthermore, Patent Document 3 describes a dosage form comprising a composition containing a microbiome control factor, the goal of which is to release the above-mentioned composition substantially in one or more of the stomach, small intestine or large intestine, and various sugars and sugar alcohols such as turanose and maltulose are listed as microbiome control factors.

[0006] On the other hand, oligofructose is known to be used as a component of specific health foods. Its ingestion promotes the proliferation of bifidobacteria present in the large intestine, and exhibits an intestinal conditioning effect through the proliferation of bifidobacteria itself or the action of short-chain fatty acids produced by bifidobacteria. In addition, it is known that the production of short-chain fatty acids lowers the pH in the large intestine, resulting in an increase in the solubility of minerals, which facilitates passage through mucosal cells and promotes their absorption by cells (Non-Patent Document 7).

[0007] Prior art literature

[0008] Patent Literature

[0009] Patent Document 1: Japanese Patent Application Laid-Open No. 2005-34135

[0010] Patent Document 2: WO2007 / 107295 (Japanese Patent Publication No. 2009-530326)

[0011] Patent Document 3: Japanese Patent Application Laid-Open No. 2018-513196

[0012] Non-patent literature

[0013] Non-patent document 1: Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis. Gut.2019Feb; 68(2):248-262

[0014] Non-patent literature 2: Parabacteorides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bileacids. Cell Rep. 2019 Jan 2; 26(1): 222-235

[0015] Non-patent document 3: Parabacteroides distasonis attenuates toll-like receptor4signaling and Akt activation and blocks coon tumor formation in high-fatdiet-fed azoxymethane-treated mice. Koh et al., Int.J.Cancer.2018; 143(7):1797-1805

[0016] Non-patent document 4: Gut bacteria from multiple sclerosis patients modulatehuman T cells and exacerbate symptoms in mouse models. Cekanaviciute et al., Proc. Natl. Acad. Sci. USA. 2017; 114(70): 10713-10718

[0017] Non-patent document 5: Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach. Del Chierico et al, Hepatology. 2017; 65(2): 451-464

[0018] Non-patent document 6: Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide. Gut microbiota2022;71,

[0019] Non-patent document 7: Absorption-promoting effect of indigestible sugar (Fructus sugar). Journal of the Japanese Society of Nutrition and Food, Vol. 52, No. 6, 387-395 Summary of the Invention

[0020] Problems to be solved by the invention

[0021] Parabacteroides bacteria are considered beneficial intestinal bacteria. However, Parabacteroides bacteria are not commonly used as probiotics, and their consumption is relatively limited. Therefore, the safety and digestive tract permeability of compositions containing Parabacteroides bacteria when taken orally remain unclear. Furthermore, even when taken orally, Bifidobacteria have difficulty reaching the intestines. Increasing the presence of these bacteria in the intestinal flora through the use of specific prebiotics is considered a useful approach in practical applications.

[0022] Solutions for solving problems

[0023] The present invention provides the following solutions:

[0024] [1] A composition for controlling the growth of Parabacteroides bacteria, comprising any one selected from trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any one of these as a constituent sugar.

[0025] [2] The composition according to item 1, which is used for promoting the growth of bacteria belonging to the genus Bifidobacterium.

[0026] [3] The composition according to 1 or 2, which is used as a prebiotic or synbiotic.

[0027] [4] A composition for treating any one selected from the group consisting of inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorder, multiple sclerosis, fatty liver and cancer, comprising any one selected from trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any one of these as constituent sugars.

[0028] [5] The composition according to 4, wherein the treatment is performed by promoting the growth of Parabacteroides bacteria in the intestine.

[0029] [6] A composition for treating a disease or condition that is improved by promoting the proliferation of Parabacteroides bacteria in the intestine, comprising any one selected from trehalulose, isomaltulose, turanose, and maltulose, and an oligosaccharide containing any of these as a constituent sugar.

[0030] [7] The composition according to any one of 1 to 6, wherein the Parabacteroides bacteria include Parabacteroides distichous.

[0031] [8] A composition for controlling the growth of Bifidobacterium bacteria, comprising any one selected from trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any one of these as a constituent sugar.

[0032] [9] A composition for promoting mineral absorption and conditioning any of the intestinal tracts, comprising any of the following: trehalulose, isomaltulose, turanose, maltulose, and oligosaccharides containing any of these as constituent sugars.

[0033]

[10] The composition according to item 9, which is based on promoting the growth of Bifidobacterium bacteria in the intestine.

[0034]

[11] A composition for treating a disease or condition that is improved by promoting the proliferation of Bifidobacterium bacteria in the intestine, comprising any one selected from trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these as constituent sugars.

[0035]

[12] The composition according to any one of 1 to 11, which contains any one selected from trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars, in the form of a composition containing any one of trehalulose and isomaltulose obtained by allowing dextran sucrase to act on a composition containing sucrose.

[0036]

[13] The composition according to item 12, wherein the dextran sucrase is produced by lactic acid bacteria or a processed product thereof.

[0037]

[14] A method for producing any one selected from trehalulose, isomaltulose, and oligosaccharides containing any one of these as constituent sugars, characterized in that dextran sucrase is allowed to act on a composition containing sucrose.

[0038]

[15] The production method according to item 14, wherein the dextran sucrase is produced by lactic acid bacteria or a processed product thereof.

[0039]

[16] The production method according to item 14 or 15, wherein the glucansucrase is used in the form of lactic acid bacteria expressing glucansucrase, and the glucansucrase is of a bacterial cell-bound type.

[0040]

[17] The production method according to any one of 14 to 16, wherein the lactic acid bacteria is Liquorilactobacillus satsumensis.

[0041]

[18] A food information providing device comprising:

[0042] an information acquisition unit, for acquiring information about the intestinal flora of the subject;

[0043] a deriving unit for deriving information about food to be provided to the subject based on the information about the intestinal flora; and

[0044] a providing unit, providing the derived food information to the object,

[0045] The information acquisition unit acquires information on the presence or quantity of Parabacteroides bacteria or Bifidobacterium bacteria from information on the intestinal flora, and the derivation unit derives information on the food based on the information on the presence or quantity of Parabacteroides bacteria or Bifidobacterium bacteria, wherein the food is a composition containing any one selected from trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars.

[0046]

[19] The device according to 18, wherein the provided food information can be displayed on the terminal of the subject.

[0047]

[20] The device according to item 18 or 19, further comprising a display unit for displaying the provided food information.

[0048]

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

[0049] obtaining information about the subject's intestinal flora;

[0050] Based on the information about the intestinal flora, information about the food provided to the subject is derived; then

[0051] providing the derived food information to the subject,

[0052] In the information acquisition step, information on the presence or quantity of Parabacteroides bacteria or Bifidobacterium bacteria is acquired from the intestinal flora information, and in the food information deriving step, food information is derived based on the information on the presence or quantity of Parabacteroides bacteria or Bifidobacterium bacteria, wherein the food is a composition comprising any one selected from trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these as constituent sugars.

[0053]

[22] The method according to 21 further includes a step of displaying the provided food information on the subject's terminal.

[0054]

[31] A composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, for use in the following method: a method for controlling the proliferation of Parabacteroides bacteria. Use of any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, in the manufacture of a composition for controlling the proliferation of Parabacteroides bacteria. A method or non-therapeutic method for controlling the proliferation of Parabacteroides bacteria, comprising the step of administering to a subject a composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars. Use or non-therapeutic use of a composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars for controlling the proliferation of Parabacteroides bacteria.

[0055]

[32] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to 31, wherein the composition is used to promote the growth of bacteria of the genus Bifidobacterium.

[0056]

[33] The composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use according to 31 or 32, wherein the composition is used as a prebiotic or synbiotic.

[0057]

[34] A composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars, for use in the following method: a method for treating any one of inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorder, multiple sclerosis, fatty liver and cancer. Use of any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars in the manufacture of a composition for treating any one of inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorder, multiple sclerosis, fatty liver and cancer. A method or non-therapeutic method for treating any one of inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorder, multiple sclerosis, fatty liver and cancer, comprising the step of administering to a subject a composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars. Use or non-therapeutic use of a composition comprising any one selected from trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars, for treating any one selected from inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorders, multiple sclerosis, fatty liver and cancer.

[0058]

[35] The composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use according to 34, wherein the treatment is carried out by promoting the proliferation of Parabacteroides bacteria in the intestine.

[0059]

[36] A composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, for use in the following method: a method for treating a disease or condition that is improved by promoting the proliferation of Parabacteroides bacteria in the intestine. Use of any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, in the manufacture of a composition for treating a disease or condition that is improved by promoting the proliferation of Parabacteroides bacteria in the intestine. A method or non-therapeutic method for treating a disease or condition that is improved by promoting the proliferation of Parabacteroides bacteria in the intestine, comprising the step of administering to a subject a composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars. Use or non-therapeutic use of a composition comprising any one selected from trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these as constituent sugars, for treating a disease or condition that is improved by promoting the growth of Parabacteroides bacteria in the intestine.

[0060]

[37] The composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use according to any one of 31 to 36, wherein the Parabacteroides bacterium includes Parabacteroides dieldrinii.

[0061]

[38] A composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, for use in the following method: a method for controlling the proliferation of Bifidobacterium bacteria. Use of any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, in the manufacture of a composition for controlling the proliferation of Bifidobacterium bacteria. A method or non-therapeutic method for controlling the proliferation of Bifidobacterium bacteria, comprising the step of administering to a subject a composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars. Use or non-therapeutic use of a composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, for controlling the proliferation of Bifidobacterium bacteria.

[0062]

[39] A composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, for use in the following method: a method for promoting mineral absorption and conditioning any of the intestinal tract. Use of any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, in the manufacture of a composition for promoting mineral absorption and conditioning any of the intestinal tract. A method for promoting mineral absorption and conditioning any of the intestinal tract or a non-therapeutic method, comprising the step of administering to a subject a composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars. Use of a composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, for promoting mineral absorption and conditioning any of the intestinal tract or a non-therapeutic use.

[0063]

[40] The composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use according to 39, which is based on promoting the proliferation of Bifidobacterium bacteria in the intestine.

[0064]

[41] A composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, for use in the following method: a method for treating a disease or condition that is improved by promoting the proliferation of Bifidobacterium bacteria in the intestine. Use of any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars, in the manufacture of a composition for treating a disease or condition that is improved by promoting the proliferation of Bifidobacterium bacteria in the intestine. A method or non-therapeutic method for treating a disease or condition that is improved by promoting the proliferation of Bifidobacterium bacteria in the intestine, comprising the step of administering to a subject a composition comprising any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides having any of these as constituent sugars. Use of a composition comprising any one selected from trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any one of these as a constituent sugar, for treating a disease or condition that is improved by promoting the growth of Bifidobacterium bacteria in the intestine.

[0065]

[42] The composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use according to any one of 31 to 41, wherein the composition comprises any one selected from trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars, in the form of a composition comprising any one of trehalulose and isomaltulose obtained by allowing dextran sucrase to act on a composition comprising sucrose.

[0066]

[43] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to 42, wherein the glucansucrase is lactic acid bacteria or a processed product thereof.

[0067] Effects of the Invention

[0068] According to the present invention, the intestinal flora can be improved, and in particular, the increase of Parabacteroides bacteria and Bifidobacterium bacteria in the intestinal flora can be promoted.

[0069] By promoting the growth of Parabacteroides bacteria in the intestinal flora, it can be expected that any type selected from inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorders, multiple sclerosis, fatty liver and cancer can be treated. In addition, by promoting the growth of Parabacteroides bacteria and Bifidobacterium bacteria in the intestinal flora, it can be expected that various diseases or conditions can be treated.

[0070] By adding the active ingredient of the present invention, functional foods in various forms can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0071] Figure 1 Figure 2. Changes in the occupancy of Parabacteroides bacteria in a culture system of four human stool samples induced by trehalulose, isomaltulose, turanose, and maltulose.

[0072] Figure 2 The changes in the occupancy of Bifidobacterium bacteria in a human stool culture system of four people were caused by trehalulose, isomaltulose, turanose, and maltulose.

[0073] Figure 3 This is an LCMS analysis of the sugar composition after mixing 65 w / w% sucrose and 0.5 w / w% enzyme solution (Lactobacillus satsumensis JCM12392) and reacting them at 48°C under static conditions for 24 hours.

[0074] Figure 4 The amino acid sequence of the dextran sucrase used in one embodiment is shown in Figure 1. The underlined sites are important for the target enzyme activity.

[0075] FIG5 is an amino acid sequence of dextran sucrase used in one embodiment. DETAILED DESCRIPTION

[0076] This embodiment relates to a composition for improving intestinal flora, comprising trehalulose, isomaltulose, turanose, and maltulose, as well as oligosaccharides containing any of these as constituent sugars, as active ingredients. More specifically, it relates to controlling the growth of Parabacteroides bacteria and promoting the growth of Bifidobacterium bacteria in the intestinal flora.

[0077] [Active ingredient]

[0078] The composition of the present embodiment comprises any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides with any of these as constituent sugars as an effective ingredient. With respect to the present invention, when referring to an oligosaccharide containing a certain sugar as a constituent sugar, the sugar itself is not included. It should be noted that, with respect to the present invention, when referring to "any one", it is used in the sense of "at least one" except where otherwise specified. For example, "selected from trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides with any of these as constituent sugars" includes, in addition to the case of only trehalulose, isomaltulose, turanose or maltulose, and the case of one oligosaccharide containing only any of these as constituent sugars, trehalulose, isomaltulose, turanose or maltulose, and the case of trehalulose, isomaltulose, turanose or maltulose and one oligosaccharide with any of these as constituent sugars, and the case of two oligosaccharides with trehalulose, isomaltulose, turanose or maltulose as constituent sugars.

[0079] Trehalulose (Glc-α1,1-Fru), isomaltulose (Glc-α1,6-Fru), turanose (Glc-α1,3-Fru), maltulose (Glc-α1,4-Fru) and leucrose (Glc-α1,5-Fru) are all structural isomers of sucrose (Glc-α1,2-β-Fru), and are all disaccharides formed by glucose and fructose.

[0080] In one embodiment, the active ingredient of the composition is any one selected from disaccharides formed by bonding (condensing) glucose and fructose and oligosaccharides having these as constituent sugars. In this case, leuconostoc and oligosaccharides having these as constituent sugars may be excluded from the active ingredient.

[0081] In another embodiment, the active ingredient of the composition is any one selected from α-D-glucopyranosyl-(1→n)-D-fructose (n represents a position 1 to 6) and oligosaccharides thereof as constituent sugars. In this case, leucrose and oligosaccharides thereof as constituent sugars may be excluded from the active ingredient.

[0082] In another embodiment, the active ingredient of the composition is any one selected from the group consisting of disaccharides represented by the following formula and oligosaccharides having the disaccharides as constituent sugars.

[0083]

[0084] Wherein, R is 1-D-fructose, 3-D-fructose, 4-D-fructose or 6-D-fructose.

[0085] Trehalulose, isomaltulose, turanose, and maltulose, as well as oligosaccharides containing any of these as constituent sugars, used in the composition may be any type as long as they exhibit the desired effect, without particular limitation. Furthermore, trehalulose, isomaltulose, turanose, and maltulose, as well as oligosaccharides containing any of these as constituent sugars, used in the composition may be one type or a combination of two or more types.

[0086] Examples of oligosaccharides containing trehalulose, isomaltulose, turanose, or maltulose as constituent sugars include oligosaccharides having 1 to 7, preferably 2 to 6, more preferably 3 to 4, and even more preferably 1 to 2 monosaccharides bonded to trehalulose, isomaltulose, turanose, or maltulose.

[0087] In one embodiment, the composition contains any one selected from trehalulose and isomaltulose.

[0088] Oligosaccharides containing a certain sugar as a constituent sugar can produce that sugar in the subject's digestive tract after administration. Therefore, any oligosaccharide containing any of trehalulose, isomaltulose, turanose, and maltulose as a constituent sugar can exert the same effects on the intestinal flora as trehalulose, isomaltulose, turanose, and maltulose.

[0089] About the trehalulose used in the present embodiment, isomaltulose, turanose and maltulose and the oligosaccharides constituting sugar with any of these, its source, manufacture method are not particularly limited, and can be manufactured by any method such as fermentation, enzymatic method, organic synthesis method.As the example of manufacture method, the manufacture method including following step can be enumerated: make glucansucrase or the lactic acid bacteria expressing glucansucrase or its processed material act on the composition comprising sucrose, obtain the composition comprising galactosyl kojibiose.With regard to the present invention, unless otherwise indicated, glucansucrase refers to the enzyme belonging to glycoside hydrolase (glycoside hydrolase) (also referred to as glycosyl hydrolases) family 70 (GH70) (reference (CAZy) databases, and Cantarel et al., Nucleic Acids Res.37:D233-238,2009).

[0090] Examples of the glucansucrase used in this embodiment include glucansucrase composed of the following proteins (A), (B), or (C). The glucansucrase composed of the following proteins (A), (B), or (C) may be in the form of lactic acid bacteria expressing glucansucrase or a processed product thereof. In this case, glucansucrase can also be used in the production method of this embodiment.

[0091] (A) A protein consisting of the amino acid sequence described in any one of SEQ ID NOs: 1 to 8; (B) A protein consisting of an amino acid sequence having high sequence identity to the amino acid sequence described in any one of SEQ ID NOs: 1 to 8 and having glucansucrase activity; (C) A protein consisting of an amino acid sequence in which one or more amino acids are substituted, deleted, inserted, and / or added to the amino acid sequence described in any one of SEQ ID NOs: 1 to 8 and having glucansucrase activity.

[0092] In one embodiment, the glucansucrase is composed of the following protein (B') or (C'). (B') A protein having high sequence identity to the amino acid sequences described in SEQ ID NOs: 1 to 8, wherein the amino acid sequence is identical to the portions corresponding to positions 450-467, 488-499, and 559-573 of SEQ ID NO: 1, and having glucansucrase activity; (C') A protein having one or more amino acids substituted, deleted, inserted, and / or added to the amino acid sequences described in SEQ ID NOs: 1 to 8, wherein the amino acid sequence is identical to the portions corresponding to positions 450-467, 488-499, and 559-573 of SEQ ID NO: 1, and having glucansucrase activity.

[0093] Sequence number 1 shows the amino acid sequence of the constitutively expressed and cell-bound glucansucrase GTF21 derived from Lactobacillus rubrum. Positions 450-467, 488-499, and 559-573 of the sequence are known to be important for glucansucrase activity (Non-Patent Document 8: J. Agric. Food Chem. 2011, 59, 4148-4155).

[0094] Sequence numbers 2-4 show the amino acid sequence of the glucansucrase (GTF68, GTF29, GFT39) possessed by red-striped liquid lactobacillus and the glucansucrase with the sequence other than sequence number 1. Sequence number 5 shows the amino acid sequence (accession number AAB40875) of the glucansucrase possessed by Leuconostoc meseteroides. Sequence number 6 shows the amino acid sequence (accession number ACY92456) of the glucansucrase possessed by Leuconostoc citreum. Sequence number 7 shows the amino acid sequence (accession number AAN58705) of the glucansucrase possessed by Streptococcus mutans. Sequence number 8 shows the amino acid sequence (accession number AAU08001) of the glucansucrase possessed by Lactobacillus reuteri.

[0095] The sequence identities of each sequence with the amino acid sequence of SEQ ID NO: 1 are shown below and in Figure 5 . Specifically, these values ​​were calculated using the BLAST algorithm (http: / / www.ncbi.nlm.nih.gov / BLAST / ) provided by NCBI (National Center for Biotechnology Information) for comparative analysis of protein amino acid sequences (BLASTP). Sequence number 2: 49%; Sequence number 3: 62%; Sequence number 4: 48%; Sequence number 5: 46%; Sequence number 6: 45%; Sequence number 7: 47%; and Sequence number 8: 56%.

[0096] The portion at positions 559 to 573 of SEQ ID NO: 1 corresponds to conserved sequence 4 of Non-Patent Document 8. In one embodiment, the glucansucrase used is composed of the protein of (B) or (C), and in this case, regardless of the sequence of the other parts of the glucansucrase, the glucansucrase is selected from:

[0097] The amino acid corresponding to position 565 of SEQ ID NO: 1 (H),

[0098] The amino acid corresponding to position 566 of SEQ ID NO: 1 (D),

[0099] The amino acid corresponding to position 567 of SEQ ID NO: 1 (S),

[0100] The amino acid corresponding to position 571 of SEQ ID NO: 1 (D) and

[0101] One or more, preferably two or more, more preferably three or more, and even more preferably all of the amino acids (Q) corresponding to position 572 of SEQ ID NO: 1 are identical to those of SEQ ID NO: 1. Positions 566-567 and 571-572 of SEQ ID NO: 1 are important as recognition sites for the receptor (lactose in this embodiment) (Non-Patent Document 8). Positions 565-566 of SEQ ID NO: 1 are highly conserved among glucansucrases.

[0102] The portion at positions 488 to 499 of SEQ ID NO: 1 corresponds to conserved sequence 3 of Non-Patent Document 8. In one embodiment, the glucansucrase used is composed of the protein of (B) or (C). In this case, regardless of the sequence of the other parts of the glucansucrase, one or more, preferably two or more, more preferably three or more, and even more preferably all of the residues selected from positions 488 to 493 (HLSILE) of SEQ ID NO: 1 are identical to those of SEQ ID NO: 1. In a particularly preferred embodiment, regardless of the sequence of the other parts, the amino acid (H) corresponding to position 488 of SEQ ID NO: 1 and the amino acid (E) corresponding to the position of SEQ ID NO: 1 are identical.

[0103] The portion at positions 450 to 467 of SEQ ID NO: 1 corresponds to the conserved sequence 2 of Non-Patent Document 8. In one embodiment, the glucansucrase used is composed of the protein of (B) or (C). In this case, the glucansucrase is selected from the group consisting of:

[0104] The amino acid corresponding to position 453 of SEQ ID NO: 1 (R),

[0105] The amino acid corresponding to position 455 of SEQ ID NO: 1 (D),

[0106] The amino acid corresponding to position 456 of SEQ ID NO: 1 (A) and

[0107] One or more, preferably two or more, more preferably three or more, and even more preferably all of the amino acids (D) corresponding to position 458 of SEQ ID NO: 1 are identical to those of SEQ ID NO: 1.

[0108]

Table 1

[0109]

[0110] The dextran sucrase used is preferably an enzyme having an activity of catalyzing the reaction of decomposing sucrose into glucose and fructose and the reaction of adding glucose to the glucan chain, and is preferably an enzyme having any one of the following activities selected from the group consisting of dextran sucrase (EC 2.4.1.5) activity, alternan sucrase (EC 2.4.1.140) activity, reuteran sucrase (EC 2.4.1.-) activity, α-4,6-glucanotransferase (EC 2.4.1.-) activity, α-1,2-branched dextran sucrase (EC 2.4.1.-) activity, α-4,3-glucanotransferase (EC 2.4.1.-) activity, and mutan sucrase (EC 2.4.1.372) activity, and more preferably at least dextran sucrase (EC 2.4.1.5) activity. 2.4.1.5) Activity.

[0111] In the present invention, whether a protein has glucansucrase activity can be determined by whether the protein has dextransucrase (EC 2.4.1.5) activity, alternansucrase (EC 2.4.1.140) activity, reutlandinsucrase (EC 2.4.1.-) activity, α-4,6-glucanotransferase (EC 2.4.1.-) activity, α-1,2-branched dextransucrase (EC 2.4.1.-) activity, and α-4,3-glucanotransferase (EC 2.4.1.-) activity. More preferably, whether a protein has glucansucrase activity can be determined by whether the protein has dextransucrase (EC 2.4.1.5) activity.

[0112] Regarding the amino acid sequence of glucansucrase, high sequence identity refers to an identity value of 45% or more, 46% or more, 47% or more, 48% or more, 49% or more, 50% or more, 56% or more, 62% or more, preferably 63% or more, 70% or more, more preferably 80% or more, further preferably 90% or more, further preferably 95% or more, and further preferably 98% or more.

[0113] With regard to the present invention, when referring to amino acid sequences, when referring to identity, except for the case of special records, it refers to the percentage of the number of consistent amino acids that are present between the two sequences when the two sequences are arranged in an optimal manner. The search / analysis of the identity of the amino acid sequence can be performed by an algorithm or program well known to those skilled in the art, such as GENETIX (registered trademark) ver.14 (GENETIX Co., Ltd.), BLASTN, BLASTP, BLASTX, ClustalW. The parameters when using the program can be appropriately set by those skilled in the art, and the default parameters of each program can also be used in addition. The specific methods of these analytical methods are also well known to those skilled in the art.

[0114] With regard to the present invention, when referring to an amino acid sequence consisting of substitution, deletion, insertion and / or addition of one or more amino acids, the number of amino acids substituted, etc., is not particularly limited as long as the protein consisting of the amino acid sequence has the target activity, except for the cases where there are special records. For the glucansucrase consisting of the sequence of SEQ ID NO: 1 consisting of a full-length 1075 amino acid sequence, for example, it refers to less than 50% (specifically, 537 or less), preferably 37% or less (specifically, 409 or less), more preferably 200 or less, further preferably 100 or less, further preferably 50 or less, further preferably 20 or less, and further preferably 1 to 9. If it is substituted with an amino acid with similar properties, a larger number of substitutions may be present. The means for preparing polynucleotides or proteins involving such amino acid sequences are well known to those skilled in the art.

[0115] In the present invention, the amino acid equivalent to position x (position x from the N-terminus) of a reference sequence (e.g., SEQ ID NO: 1) in a certain amino acid sequence S refers to the amino acid in sequence S that corresponds to the amino acid at position x in the reference sequence when sequence S and the reference sequence are aligned. In cases where the position of the corresponding amino acid in sequence S is missing one or more amino acids in the reference sequence, the position may be offset from that in the reference sequence and may not be position x in sequence S. A person skilled in the art can appropriately determine which amino acid in sequence S the amino acid equivalent to position x in the reference sequence corresponds to.

[0116] When lactic acid bacteria are used, those expressing glucansucrase are preferred. Preferred examples of lactic acid bacteria include those belonging to the family Leuconostocaceae, more preferably those belonging to the genus Leuconostoc, and even more preferably Leuconostoc mesenteroides.

[0117] When lactic acid bacteria are used, those that constitutively express glucansucrase are preferred. Preferred examples of lactic acid bacteria are lactic acid bacteria belonging to the family Lactobacillus (Lactobacillaceae), more preferably lactic acid bacteria belonging to the genus Liquorilactobacillus (Liquorilactobacillus) or lactic acid bacteria belonging to the genus Limosilactobacillus (Limosilactobacillus), and even more preferably Limosilactobacillus reuteri and Liquorilactobacillus satsumensis.

[0118] When using lactic acid bacteria, it is preferably a lactic acid bacteria that constitutively expresses glucan sucrase, and glucan sucrase is more preferably a thalline binding type. The example of preferred lactic acid bacteria is a lactic acid bacteria belonging to the Lactobacillus (Lactobacillaceae) family, more preferably a lactic acid bacteria belonging to the genus Liquorilactobacillus (Liquorilactobacillus), further preferably red stripe liquid lactobacillus (Liquorilactobacillus satsumensis). The example of the bacterial strain of particularly preferred red stripe liquid lactobacillus (Liquorilactobacillus satsumensis) is JCM12392. It should be noted that JCM12392 is described as red stripe lactobacillus (Lactobacillus satsumensis) in RIKEN BioResource Center, GENERAL CATALOG No.9, 2012, JAPAN COLLECTION OFMICROORGANISMS, M51.

[0119] It should be noted that, with respect to the present 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.: Ataxonomic 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. According to the classification before re-editing, red-striped liquid Lactobacillus is classified as red-striped Lactobacillus (Lactobacillus satsumensis).

[0120] The lactic acid bacteria expressing glucansucrase or a processed product thereof is preferably any one selected from the group consisting of living bacteria, dead bacteria, a culture containing bacteria, a disrupted bacterial cell product, and a purified product of glucansucrase.

[0121] Glucansucrase used for producing oligosaccharides containing any of trehalulose, isomaltulose, turanose, and maltulose as constituent sugars, or lactic acid bacteria expressing glucansucrase or processed products thereof can be produced using transformation, chemical synthesis, or genome editing techniques.

[0122] A composition containing any of trehalulose, isomaltulose, turanose, and maltulose obtained by such a production method can be used directly as a solution containing any of trehalulose, isomaltulose, turanose, and maltulose, or can be purified using an ion exchange resin or the like. Specifically, the composition of this embodiment can be a composition containing any of trehalulose and isomaltulose obtained by allowing glucansucrase or lactic acid bacteria expressing glucansucrase, or a processed product thereof, to act on a composition containing sucrose, more preferably a composition containing any of trehalulose, isomaltulose, turanose, and maltulose. Such a composition can contain any of leucrose and kojibiose.

[0123] [use]

[0124] (Function / Effect)

[0125] The composition of this embodiment can be used to improve intestinal flora.

[0126] Improving the intestinal flora includes controlling the growth of Parabacteroides bacteria. Control includes both upregulation (promotion, increase, inhibition of decrease) and downregulation (inhibition, decrease, inhibition of increase). Additionally, improving the intestinal flora includes promoting the growth of Bifidobacterium bacteria.

[0127] In the present invention, references to Parabacteroides bacteria refer to bacteria identified as such using molecular phylogenetic analysis based on the 16S rRNA gene. The same applies to Bifidobacterium bacteria. The criteria for identifying bacterial genus using molecular phylogenetic analysis based on the 16S rRNA gene are well known to those skilled in the art (Stackebrandt E, Ebers J. Taxonomic parameters revisited: tarnished gold standards. Microbiol Today 2006; 33: 152-155).

[0128] Regarding improving the intestinal flora, promoting the proliferation of specific bacteria means increasing the proportion (occupancy rate) of specific bacteria in the intestinal flora.

[0129] Whether a certain component promotes the proliferation of specific bacteria in the intestinal flora can be evaluated as follows. Add feces provided by a healthy person to a suitable culture medium, culture for a certain period of time as needed, add the component to be evaluated, culture under appropriate conditions (for example, culture for 48 hours at 37°C and anaerobic conditions similar to intestinal conditions), and measure the occupancy rate of specific bacteria in the flora in the culture. Then, compare the measurement results with the measurement results of a culture cultured under the same conditions except that a control (such as sterilized water) is added instead of the component to be evaluated. When the occupancy rate is higher than that of the control, it can be judged that the proliferation is promoted, and when the occupancy rate is lower than that of the control, it can be judged that the proliferation is inhibited.

[0130] The occupancy rate of specific bacteria contained in the flora can be obtained by known methods. One of the preferred methods is to perform 16S metagenomic analysis (sequence analysis of 16S rRNA gene amplicons) on DNA extracted from the culture. When implementing 16S metagenomic analysis, DNA extraction can be performed using commercially available kits. The genomic region analyzed is not particularly limited as long as the bacteria can be determined, but the V3-V4 region of the 16S rRNA gene can be used. Methods such as primers, amplification conditions, and purification of amplicons used for bacterial analysis can also use methods well known to those skilled in the art. Sequence interpretation is preferably performed using a next-generation sequencer with higher performance. The analysis of the obtained data can be performed using QIIME 2 TM For 16S metagenomic analysis, those skilled in the art can refer to Sanschagrin S, Yergeau E. Next-generation sequencing of 16S ribosomal RNA geneamplicons. J Vis Exp. 2014; (90): 51709. Published 2014 Aug 29. doi: 10.3791 / 51709.

[0131] The Parabacteroides bacteria of the present invention are bacteria that inhabit the intestinal tract. By promoting the proliferation of Parabacteroides bacteria, it is expected to have an effect on inflammation, obesity, glucose metabolism disorders, fatty liver and cancer (non-patent literature 1 to 3). In addition, it is reported that: Parabacteroides distasonis (P.distasonis) is reduced in patients with multiple sclerosis (MS) (non-patent literature 4), and a combination of Parabacteroides bacteria, Oscillospira bacteria, Rickenellaceae bacteria and Parabacteroides bacteria can distinguish between patients with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRLs) (non-patent literature 5). Therefore, the composition can be used to treat any species selected from the group consisting of inflammation, obesity, glucose metabolism disorders, multiple sclerosis (MS), fatty liver and cancer.

[0132] In addition, it has been reported that oral administration of Parabacteroides goldsteinii in a smoking-induced COPD model mouse model improved weight loss and the increase in inflammatory cytokines in lung tissue. The mechanism of this is suggested to be that pentaacyl lipopolysaccharide, a cell wall component of Parabacteroides goldsteinii, antagonizes TLR4 receptor activation caused by inflammatory hexaacyl lipopolysaccharides from intestinal bacteria (Non-Patent Document 6). Therefore, the composition can be used to treat COPD.

[0133] Inflammation includes inflammatory bowel disease, which includes ulcerative colitis and Crohn's disease. Obesity refers to a condition characterized by excessive body fat accumulation (BMI of 25 or higher). Obesity is considered a condition when it causes adverse health effects, or when it manifests as visceral fat obesity. Disorders of glucose metabolism are abnormalities in glucose metabolism, including insulin resistance and diabetes. Insulin resistance occurs when the pancreas secretes insulin into the bloodstream, but target organs become less sensitive to insulin, weakening the effects of insulin. Insulin resistance reduces the ability of muscle and adipose tissue to absorb glucose, and the liver is unable to suppress gluconeogenesis. Consequently, blood sugar levels remain difficult to lower, requiring increased insulin to return to normal. If this condition persists, pancreatic insulin secretion decreases, blood sugar levels rise, and type 2 diabetes develops. Insulin resistance can be caused by genetics, obesity, lack of exercise, a high-fat diet, or stress. Diabetes refers to chronic, persistent hyperglycemia caused by insufficient insulin action, and includes both type 1 and type 2 diabetes. Multiple sclerosis (MS) is a demyelinating disease that is spatially and temporally multiple in the central nervous system (brain / spinal cord / optic nerve), including relapsing-remitting, primary progressive, and secondary progressive types. Fatty liver disease includes fatty liver (fatty liver disease), alcoholic fatty liver disease, non-alcoholic fatty liver disease (NAFLD), and simple fatty liver disease. Cancer includes lung cancer, breast cancer, stomach cancer, colon cancer, liver cancer, kidney cancer, pancreatic cancer, uterine cancer, ovarian cancer, head and neck cancer, osteosarcoma, chondrosarcoma, rhabdomyosarcoma, leiomyosarcoma, fibrosarcoma, liposarcoma, angiosarcoma, leukemia, malignant lymphoma, and myeloma. Chronic obstructive pulmonary disease is sometimes also referred to as emphysema or chronic bronchitis. It is said that the main cause is smoking. When COPD develops, it not only affects the lungs, but also affects organs throughout the body, making it easy to develop diabetes, arteriosclerosis, osteoporosis, peptic ulcers, etc.

[0134] Furthermore, the composition can be used to treat diseases or conditions that are improved by promoting the growth of Parabacteroides bacteria in the intestine. Such diseases or conditions include inflammation, chronic obstructive pulmonary disease (COPD), obesity, glucose metabolism disorders, multiple sclerosis (MS), fatty liver, and cancer, as well as various other diseases or conditions.

[0135] Bifidobacterium bacteria is a bacterium that inhabits the intestinal tract and produces short-chain fatty acids (mainly lactic acid and acetic acid) from glucose. The effect of the short-chain fatty acids produced by Bifidobacterium bacteria or Bifidobacterium bacteria is known to show an intestinal conditioning effect, and if short-chain fatty acids are generated, the pH in the large intestine decreases, and as a result, the solubility of minerals increases, and it becomes easy to pass through mucosal cells, promoting its absorption by cells (the mineral absorption promoting effect of indigestible saccharides (oligofructose). Japanese Nutrition / Food Society Journal Vol. 52, No. 6, 387-395). Therefore, the composition can be used for conditioning the intestinal tract and promoting the absorption of minerals. As the example of minerals, calcium, magnesium, iron, potassium, zinc, copper, chromium, manganese, molybdenum, iodine, sodium, phosphorus, selenium can be listed. By the composition, it can be expected that the absorption of calcium, magnesium and iron in them can be particularly promoted.

[0136] Furthermore, the composition can be used to treat diseases or conditions that are improved by promoting the growth of Bifidobacterium bacteria in the intestines. Such diseases or conditions can be treated by various means other than conditioning the intestines and promoting mineral absorption.

[0137] When referring to a disease or condition that is improved by promoting the growth of Parabacteroides bacteria in the intestine, or a disease or condition that is improved by promoting the growth of Bifidobacterium bacteria in the intestine, the condition includes a situation where the growth of Parabacteroides bacteria or Bifidobacterium bacteria in the intestine causes the growth of intestinal bacteria that are desired to grow, or the reduction of intestinal bacteria that are desired to decrease.

[0138] With respect to the present invention, when referring to the treatment (non-therapeutic treatment) of a disease or condition, it refers to the reduction of the risk of morbidity, the delay of morbidity, prevention, assistance in treatment, cessation of disease progression, and delay. Treatment assistance is a non-therapeutic behavior, including assistance in radical therapy (treatment to remove the cause of the disease) and assistance in symptomatic therapy (treatment to improve symptoms). Details about treatment assistance will be described later. The behavior used to improve or treat includes non-therapeutic behavior performed by doctors or people other than doctors, such as pharmacists, nutritionists (including management nutritionists, sports nutritionists), health workers, midwives, nurses, clinical examination technicians, sports trainers, drug manufacturers, drug sellers, food manufacturers, food sellers, etc. Furthermore, preventing or reducing the risk of morbidity includes recommending the intake of specific foods and nutritional guidance (including nutritional guidance required for recuperation of the wounded and sick, and nutritional guidance for maintaining and improving health).

[0139] (About intestinal flora and its improvement)

[0140] Generally, the intestinal flora is not limited and may include the following bacteria.

[0141] Parabacteroides bacteria, Bifidobacterium bacteria, or Bacteroides uniformis, Alistipes putredinis, Parabacteroides merdae, Dorea longicatena, Ruminococcus bromii L2-63, Bacteroides caccae, Clostridium sp SS2-1, Bacteroides thetaiotaomicron VPI-5482, Eubacterium hallii, Ruminococcus torques L2-14, unknown sp SS3 4, Ruminococcus sp SR1 5, Faecalibacterium prausnitzii SL3 3. Ruminococcus lactaris, Collinsella aerofaciens, Dorea formicigenerans, Bacteroides vulgatus ATCC8482, Roseburia intestinalis M50 1. Bacteroides sp.2_1_7, Eubacterium siraeum 70 3. Parabacteroides distasonis ATCC 8503, Bacteroides sp.9_1_42FAA, Bacteroides ovatus, Bacteroides sp.4_3_47FAA, Bacteroides 2_2_4 sp.2_2_4), Eubacterium rectale M104 1, Bacteriodes xylanisolvens XB1A, Coprococcus comes SL7 1, Bacteroides sp.D1, Bacteroides sp.D4D4), Eubacterium ventriosum, Bacteroides dorei, Ruminococcus obeum A2-162, Subdoligranulum variabile, Bacteroides capillosus, Streptococcus thermophilus LMD-9, Clostridium leptum, Holdemania filiformis, Bacteroides stercoris, Coprococcus eutactus, Clostridium sp M62 1, Bacteroides eggerthii, Butyrivibrio crossotus, Bacteroides finegoldii, Parabacteroides johnsonii johnsonii), Clostridium sp L2-50, Clostridium nexile, Bacteroidespectinophilus, Anaerotruncus colihominis, Ruminococcus gnavus, Bacteroides intestinalis, Bacteroides fragilis 3_1_12, Clostridium asparagiforme, Enterococcus faecalis TX0104, Clostridium scindens, and Blautia hansenii (Non-Patent Document 9: JJ Qin et al. Nature 464, 59-65 (2010) doi:10.1038 / nature08821).

[0142] In addition, the bacteria in the intestinal flora usually coexist with each other while interacting with each other. Therefore, it is believed that when the specific bacteria in the intestinal flora increase (occupancy rate increases), the bacteria will affect each other and cause the proliferation of target bacteria. The interaction can be a quorum effect (Quorum Sensing), substance / nutrient exchange between bacteria, substance exchange via vesicles, etc. Such interactions are sometimes called exchanges, or chemical exchanges because they are exchanges with the help of chemical substances. In addition, organic acids (pH control) and bile acids (antibacterial effects based on surfactant effects. Sensitivity varies depending on bacteria) may affect the intestinal flora. Sometimes, the intestinal flora will become an environment that they like because specific bacteria change the pH, etc., thereby promoting proliferation (Front Microbiol.2021Jan 28:12:611413.doi:10.3389 / fmicb.2021.611413., Nature (2021), volume 599, pages458-464).

[0143] The improvement of the intestinal flora in this embodiment includes controlling the proliferation of Parabacteroides bacteria. In addition, the improvement of the intestinal flora includes promoting the proliferation of Bifidobacterium bacteria. The improvement of the intestinal flora is achieved through various upstream and downstream pathways including controlling the proliferation of Parabacteroides bacteria or promoting the proliferation of Bifidobacterium bacteria.

[0144] In one embodiment, improvement of the intestinal flora can be achieved by any of the following (it should be noted that the following description uses trehalulose, isomaltulose, turanose, and maltulose, and trehalulose among oligosaccharides containing any of these as constituent sugars as an example, but this description also applies to isomaltulose, turanose, and maltulose other than trehalulose, and oligosaccharides containing any of trehalulose, isomaltulose, turanose, and maltulose as constituent sugars. In addition, the following description uses Parabacteroides bacteria among Parabacteroides bacteria and Bifidobacterium bacteria as an example, but this description also applies to Bifidobacterium bacteria.)

[0145] (a) Growth of Parabacteroides bacteria induced by trehalulose

[0146] (b) Growth of Parabacteroides bacteria caused by at least one metabolite of trehalulose produced by at least one intestinal bacterium other than Parabacteroides bacteria (hereinafter, "intestinal bacteria other than Parabacteroides bacteria" will be referred to as "other intestinal bacteria").

[0147] (c) proliferation of Parabacteroides bacteria caused by proliferation of at least one other intestinal bacterium induced by trehalulose and reduction of at least one other intestinal bacterium that competes with Parabacteroides bacteria caused by the proliferation

[0148] (d) Proliferation of Parabacteroides mediated by trehalulose-related interbacterial communication

[0149] (e) Control of Parabacteroides bacteria by reducing other intestinal bacteria that compete with Parabacteroides bacteria due to at least one metabolite of trehalulose produced by Parabacteroides bacteria

[0150] (Target)

[0151] The composition of this embodiment is suitable for administration to the following subjects: subjects who are healthy and who desire or need to control the proliferation of Parabacteroides bacteria in the intestine; subjects who are healthy and who desire or need to promote the proliferation of Bifidobacterium bacteria in the intestine; any subject selected from the group consisting of smokers, subjects prone to constipation, diarrhea, mineral deficiency, and subjects who desire or need to supplement minerals; subjects who are healthy and who are in a disease or condition that is improved by controlling the proliferation of Parabacteroides bacteria in the intestine; and subjects who are healthy and who are in a condition that is improved by promoting the proliferation of Bifidobacterium bacteria in the intestine. Subjects who desire or need to control the proliferation of Parabacteroides bacteria in the intestine include those with a small number of Parabacteroides bacteria in the intestine. Subjects who desire or need to promote the proliferation of Bifidobacterium bacteria in the intestine include those with a small number of Bifidobacterium bacteria in the intestine. It should be noted that, with respect to the present invention, administration refers to not only the case of administering a drug to a subject, but also refers to causing the subject to ingest food other than the drug.

[0152] Healthy subjects refer to humans who have not been diagnosed with any disease (not suffering from the disease) or companion animals described below. That is, when the composition of this embodiment is used on these healthy subjects, the composition of this embodiment is not provided for therapeutic purposes.

[0153] The composition of this embodiment can also be used for non-therapeutic purposes in healthy subjects. In one embodiment, the composition of this embodiment can be used in the form of food, etc. (for example, in the form of a food composition). In the above embodiment, the composition is not provided in the form of a pharmaceutical but in the form of a supplementary food, a health food, a supplement, etc.

[0154] The composition of the present embodiment is suitable for administering to the following subjects: subjects who are suffering from a disease and who desire or need to control the proliferation of Parabacteroides bacteria in the intestine; subjects who are suffering from a disease and who desire or need to promote the proliferation of Bifidobacterium bacteria in the intestine; subjects who are suffering from a disease and are any of the species selected from the group consisting of inflammation, chronic obstructive pulmonary disease (COPD), obesity, glucose metabolism disorders, multiple sclerosis (MS), fatty liver and cancer; subjects who are suffering from a disease and who are selected from the group consisting of smokers, prone to constipation, diarrhea, mineral deficiencies and subjects who desire or need to supplement minerals; subjects who are suffering from a disease and who are in a disease or state that is improved by controlling the proliferation of Parabacteroides bacteria in the intestine; and subjects who are suffering from a disease and who are in a state that is improved by promoting the proliferation of Bifidobacterium bacteria in the intestine. Subjects who desire or need to control the proliferation of Parabacteroides bacteria in the intestine include those with a small number of Parabacteroides bacteria in the intestine. Subjects who desire or need to promote the proliferation of Bifidobacterium bacteria in the intestine include those with a small number of Bifidobacterium bacteria in the intestine. In the present invention, the term "administer" may be used to mean administering a drug to a subject, and may also mean causing a subject to ingest food or the like other than the drug.

[0155] A subject suffering from a disease is a human or companion animal diagnosed with any disease. When the composition of this embodiment is used on such a subject suffering from a disease, the composition of this embodiment is provided not for therapeutic purposes but for non-therapeutic purposes such as assisting treatment.

[0156] The composition of the present embodiment can be used for non-therapeutic purposes for objects suffering from diseases. In one embodiment, the composition of the present embodiment can be used as a composition for adjuvant therapy in the form of food or the like (e.g., food composition). Here, adjuvant therapy refers to non-therapeutic uses as the treatment of diseases or diseases. As adjuvant therapy, for example, the following can be cited: for objects treated for diseases or illnesses, a method of increasing the therapeutic effect and nutritional assistance during treatment is used for the purpose; for objects treated for diseases or illnesses, a method of improving the prognosis and nutritional assistance after treatment is used for the purpose; for objects scheduled to be treated for diseases or illnesses, a method of increasing the therapeutic effect of subsequent treatment and nutritional assistance before treatment is used for the purpose, etc. In these methods, the present composition is not provided in the form of a drug but in the form of, for example, supplementary food, health food, or a supplement.

[0157] When using the composition of this embodiment for non-therapeutic purposes, the desirability or necessity of the composition can be determined by, for example, advice provided by medical professionals such as doctors, nurses, pharmacists, midwives, and clinical technicians, as well as non-therapeutic actions. Furthermore, non-therapeutic actions can be determined by nutritionists (including management dietitians and sports nutritionists), health care professionals, physical trainers, pharmaceutical manufacturers and distributors, food manufacturers and distributors, and by the patient themselves or their family. Furthermore, these determinations include those based on the results of questionnaires on lifestyle habits, dietary habits, and subjective symptoms, as well as those based on subjective symptoms (focusing on obesity and lifestyle-related diseases).

[0158] The subject can be a human or a non-human animal. Examples of non-human animals include mammals, birds, reptiles, amphibians, fish, and the like. Non-human animals can be commercial animals, research animals, and companion animals. The term "companion animal" refers to a domestic animal or a domestic animal that serves as a companion in the home or is closely associated with one or more people on a daily basis, thereby satisfying their physical, emotional, behavioral, and social needs at any time. In one embodiment, the species included in the definition of companion animals include dogs, canines, cats, felines, cattle, horses, goats, sheep, pigs, primates (monkeys, etc.), rabbits, ferrets, rodents (guinea pigs, hamsters, mice, rats, etc.), and other small mammals. In another embodiment, the species included in the definition of companion animals are dogs, cats, horses, rabbits, ferrets, guinea pigs, and other small mammals, birds, small reptiles, fish, and domestic animals.

[0159] There is no particular limitation on the age of the subject. When the subject is a human, for example, it can be a newborn (within 28 days after birth); an infant (less than 1 year after birth); a toddler (1 to 6 years after birth); a child (over 7 years old and under 15 years old); an adult (over 15 years old); a person over 60 years old; a person over 65 years old. It should be noted that after entering old age, the number of bifidobacteria in the intestine will decrease, and some subjects cannot even be detected at all (Journal of Enterobacteriacology 25:113-124, 2011). Therefore, in one embodiment, the composition is preferably for intake by people over 65 years old. In addition, the number of Parabacteroides may decrease with age (Park et al. BMC Microbiology (2021) 21:151). Therefore, in another embodiment, the composition is preferably for intake by adults (over 15 years old), and more preferably for intake by people over 65 years old.

[0160] [Composition]

[0161] (Food composition, etc.)

[0162] The composition of the present embodiment can be made into a food composition or a pharmaceutical composition. Unless otherwise specified, food and medicine include not only food and medicine for human use, but also food and medicine for animals other than humans. Unless otherwise specified, food includes general food, functional food, nutritional composition and other non-therapeutic food (food for non-therapeutic purposes), and also includes therapeutic food (food for therapeutic purposes. Food cooked based on a diet recipe prescribed by a doctor and a menu prepared by his nutritionist, etc.), dietetic food, formula food, nursing food, therapeutic auxiliary food. Unless otherwise specified, food includes not only solid matter, but also liquid food, such as beverages, health drinks, liquid food and soup. Functional food refers to food that can impart a specified functionality to an organism, such as specific health food (including conditional special protection [specific health food]), functional labeled food, health functional food including nutritional functional food, special purpose food, nutritional supplement food, health supplement food, supplement (such as tablets, coated tablets, sugar-coated tablets, capsules, liquid preparations and other various dosage forms of food), beauty food (such as weight loss food) and other all health foods. In addition, for the purposes of the present invention, "functional foods" include health foods that carry health claims based on the food standards of the Codex Alimentarius (Joint FAO / WHO Food Standards Commission). The composition may also be a purified product of a specific sugar. Purified products include fractionated products, partially purified products, and crudely purified products.

[0163] (Administration method, etc.)

[0164] The composition of the present embodiment can be administered orally, parenterally, for example, via a tube (gastrostomy, enterostomy), or nasally, but is preferably administered orally.

[0165] The composition can be administered to a subject repeatedly or continuously for an extended period of time. The duration of administration is not particularly limited, but to fully observe the effects, continuous administration over a relatively long period of time is sufficient, for example, 3 days or more, 1 week or more, 2 weeks or more, 1 month or more, 3 months or more, 6 months or more, or 1 year or more.

[0166] The composition can be administered daily, in advance, or as needed, such as during high-risk periods. The composition can be administered as a meal, before, after, or between meals, or when the disease or condition to be improved by the composition occurs.

[0167] (Dosage, content)

[0168] The dosage of the composition of this embodiment may be any amount that can produce the desired effect. The dosage may be appropriately set in consideration of various factors such as the age, weight, and symptoms of the subject.

[0169] Furthermore, each component in the composition of the present embodiment is used at an intake amount that can ensure safety or below the acceptable daily intake (ADI), taking into account food safety laws in each country.

[0170] The daily dosage of the composition can be calculated as 0.5g or more in terms of the amount of the active ingredient, can be 1g or more, preferably 2g or more, preferably 3g or more, more preferably 5g or more, and further preferably 10g or more. The upper limit of the daily active ingredient 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 even if the lower limit is arbitrarily determined. It should be noted that when a plurality of active ingredients are included in the composition, the amount of the active ingredient refers to the total amount of the active ingredient contained.

[0171] Administration may be once a day or divided into multiple doses per day, for example, 2 to 10 doses. The amount of the active ingredient administered each time may be, for example, 0.5 g or more, 1 g or more, preferably 2 g or more, more preferably 3 g or more, and even more preferably 5 g or more. Even if the lower limit is arbitrary, the upper limit of the active ingredient administered each time may be 70 g or less, 60 g or less, 50 g or less, 40 g or less, 30 g or less, 25 g or less, or 10 g or less.

[0172] The content of the active ingredient in the composition can be appropriately set according to the form of the composition. For example, when the composition is in the form of fermented milk or a beverage that is eaten or drunk directly, 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 further preferably 0.5% or more. The upper limit value 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, even if the lower limit value is arbitrary. Alternatively, the content of the active ingredient per unit solid content of the composition can be set to 0.1% or more, preferably 1% or more, more preferably 3% or more, and further preferably 5% or more. The upper limit value of the active ingredient per unit solid content can be set to 80% or less, 50% or less, 40% or less, or 30% or less, even if the lower limit value is arbitrary. It should be noted that, with respect to the present invention, unless otherwise specified, % refers to mass %.

[0173] (Other ingredients, additives)

[0174] In the present invention, the composition may contain other active ingredients and nutritional ingredients that are permitted as food or medicine. Examples of such ingredients are lipids (e.g., milk fat, vegetable oils and fats containing medium-chain fatty acids), proteins (e.g., milk protein, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin (α-La), β-lactoglobulin (β-Lg), heat-denatured whey protein, and enzyme-treated whey protein), amino acids (e.g., lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), trehalulose, isomaltulose, Sugars other than turanose and maltulose, and oligosaccharides containing any of these as constituent sugars (glucose, sucrose, fructose, maltose, trehalose, erythritol, maltitol, xylitol, dextrin, kojibiose, galactosylkojibiose), 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 niacins), minerals (e.g., copper, zinc, iron, cobalt, manganese), antibiotics, dietary fiber, etc.

[0175] In the present invention, the composition may contain prebiotics in addition to the active ingredient. Prebiotics are indigestible food ingredients that selectively alter the growth and activity of specific bacteria in the large intestine, thereby beneficially affecting the host and improving their health. The composition may contain one or more prebiotics in addition to the active ingredient.

[0176] Prebiotics other than the active ingredient are not particularly limited as long as they do not interfere with the effects of the active ingredients contained in the composition. Examples of prebiotics other than the active ingredient include galacto-oligosaccharides, fructo-oligosaccharides, xylo-oligosaccharides, isomalto-oligosaccharides, raffinose, lactulose, lactofructo-oligosaccharides, soybean oligosaccharides, coffee oligosaccharides, dietary fiber, and gluconic acid.

[0177] Furthermore, the composition can also be used as a synbiotic, containing probiotics in addition to the active ingredient. Synbiotics are a combination of probiotics and prebiotics. Probiotics are microorganisms that, when introduced into the host's intestines in a live state, have beneficial effects on the host.

[0178] There are no particular limitations on the probiotics as long as they do not interfere with the effects of the active ingredients contained in the composition. Specific lactic acid bacteria and the like are known as examples of probiotics.

[0179] In addition, the composition may also contain additives that are permitted as food or medicine. Examples of such additives include inactive carriers (solid or liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, colorants, preservatives, buffers, pH regulators, emulsifiers, stabilizers, sweeteners, antioxidants, flavorings, acidulants, and natural products. More specifically, water, other aqueous solvents, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, vaseline, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, sucralose, stevioside, aspartame, acesulfame potassium, citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, vegetable juice, etc.

[0180] (Dosage form / form)

[0181] The food composition of the present embodiment can be made into any form such as solid, liquid, mixture, suspension, powder, granule, paste, jelly, gel, capsule, etc. In addition, the food composition of the present embodiment can be made into any form such as dairy products, supplements, snacks, beverages, health drinks, flavorings, sweeteners, processed foods, side dishes, soups, etc. More specifically, the composition of the present embodiment can be made into liquid food (semi-liquid food, concentrated liquid diet, etc.), jelly, gel, powder, formula milk powder, formula liquid milk, milk powder / liquid milk for pregnant women / breastfeeding women, fermented milk, sticks, mousse, chocolate, biscuits, ice cream, fermented milk, lactic acid bacteria beverage, milk beverage, milk beverage, refreshing drink, fruit juice beverage, sheet, cheese, bread, biscuits, crackers, pizza crust, whiskey, bourbon whiskey, spirits, liqueur, wine, fruit wine, Japanese sake , Chinese sake, shochu, beer, non-alcoholic beer with an alcohol content of less than 1%, sparkling wine, other miscellaneous wines, shochu high sticks and other alcoholic beverages, mineral water; processed products using eggs, processed products of fish, shellfish or livestock meat (including liver and other offal) (including delicacies), miso, soy sauce, rice seasonings and other condiments, soups such as miso soup, food for patients, nutritional food, frozen food, processed food and other forms. In addition, it can also be made into granules, powders, pastes, concentrates and other forms for mixing in beverages and foods. Granules and powders can be made into cubes or sticks (small packages for single doses). It should be noted that mineral water includes either sparkling or non-sparkling mineral water. With respect to the present invention, formula milk powder, as defined in Japan's "Ministerial Ordinance on Composition Standards for Milk and Dairy Products (hereinafter referred to as the "Ministerial Ordinance on Milk, etc."), refers to a powdered product made by processing fresh milk, cow's milk, special milk, fresh buffalo milk, or foods made with these as raw materials or using them as the main raw materials, to which nutrients required by infants and young children are added. With respect to the present invention, formula liquid milk, as defined in the Ministry of Milk, etc., refers to a liquid product made by processing fresh milk, cow's milk, special milk, fresh buffalo milk, or foods made with these as raw materials or using them as the main raw materials, to which nutrients required by infants and young children are added.

[0182] The pharmaceutical composition of this embodiment can be prepared into any dosage form suitable for oral administration, such as solid preparations such as tablets, granules, powders, pills, and capsules; liquid preparations such as solutions, suspensions, and syrups; and gels and aerosols.

[0183] (other)

[0184] In the manufacture of the composition of the present embodiment, the stage of compounding the active ingredient can be appropriately selected. As long as the properties of the active ingredient are not significantly damaged, the compounding stage is not particularly limited. For example, the active ingredient can be mixed with the raw materials and compounded. Alternatively, the composition containing the active ingredient can be manufactured by adding the active ingredient in the final stage of manufacture.

[0185] The composition of this embodiment may be labeled with its intended use (application) and may also be labeled with a recommendation for administration to a specific subject.

[0186] The composition of this embodiment may be labeled with the following: the composition or active ingredient can (appropriately) increase the number of Parabacteroides bacteria in the intestine (intestines, gastrointestinal tract); increase the ratio of Parabacteroides bacteria in the intestinal flora; promote the proliferation of Parabacteroides bacteria in the intestine; treat diseases or conditions that can be improved by promoting the proliferation of Parabacteroides bacteria in the intestine; can (appropriately) increase the number of Bifidobacterium bacteria (Bifidobacteria) in the intestine (intestines, gastrointestinal tract); increase the ratio of Bifidobacterium bacteria (Bifidobacteria) in the intestinal flora; promote the bifidobacteria in the intestine. The invention relates to a product that can promote the proliferation of bifidobacteria (bifidobacteria); can promote the proliferation of bifidobacteria (bifidobacteria) in the intestine; can treat diseases or conditions that can be improved by promoting the proliferation of bifidobacteria (bifidobacteria); can be used as a prebiotic; can be used as a synbiotic; can treat inflammation, chronic obstructive pulmonary disease (COPD), obesity, glucose metabolism disorders, multiple sclerosis, fatty liver and cancer; maintain a good intestinal environment; regulate intestinal flora; regulate gastrointestinal conditions; improve laxative effects; or improve the intestinal environment. In addition, it can also indicate that the product is recommended for administration to a specific subject. It should be noted that a time period such as "temporary" or "long-term" can be appropriately indicated before each sentence. The indication can be direct or indirect. Examples of direct indication include records on physical objects such as the product itself, packaging, containers, labels, and signs. Examples of indirect indication include advertising / promotional activities conducted through websites, stores, brochures, exhibitions, media seminars, books, newspapers, magazines, television, radio, mailings, emails, audio, and other places or means.

[0187] In one embodiment, the indication of the content of the recommended composition for ingestion is personalized. This indication can be provided using a document (whether written or electronic) sent to the subject, a device such as a tablet, smartphone, or personal computer, or a social media account. Furthermore, this indication can be provided in conjunction with the display of the results of any test / analysis performed on the subject, such as intestinal flora testing, fecal substance testing, and fecal metabolome analysis.

[0188] [Other embodiments]

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

[0190] an information acquisition unit, for acquiring information about the intestinal flora of the subject;

[0191] a deriving unit that derives information on food recommended to the subject based on the information on the intestinal flora; and

[0192] The providing unit provides the derived food information to the subject.

[0193] It should be noted that the information acquisition unit may include a stool collection unit and a stool pretreatment unit (freezing treatment, anaerobic storage, nucleic acid extraction / purification unit), which may be installed in the toilet bowl of the bathroom.

[0194] In a preferred embodiment, the information acquisition unit of the device acquires information on the presence or number of Parabacteroides bacteria from information on the intestinal flora, and the derivation unit derives information on the food product based on the information on the presence or number of Parabacteroides bacteria, wherein the food product is a composition comprising any species selected from the group consisting of trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these species as constituent sugars. Alternatively, the information acquisition unit of the device acquires information on the presence or number of Bifidobacterium bacteria from information on the intestinal flora, and the derivation unit derives information on the food product based on the information on the presence or number of Bifidobacterium bacteria, wherein the food product is a composition comprising trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these species as constituent sugars.

[0195] In one embodiment, a food information providing device can display the provided food information on a target device. In another embodiment, the device further includes a display unit for displaying the provided food information. The display unit can be a target device, such as a tablet terminal, a smartphone, or a personal computer.

[0196] In one embodiment, the food information providing device may include an analyzing unit that analyzes a bacterial flora of a sample obtained from a subject, and may also include an order receiving unit that receives a food order from the subject based on the recommended food information.

[0197] This embodiment also provides a method for providing food information, comprising the following steps:

[0198] obtaining information about the subject's intestinal flora;

[0199] Based on the information of the intestinal flora, information on foods recommended to the subject is derived; then

[0200] The derived food information is provided to the subject.

[0201] In a preferred embodiment, in the information acquisition step, information on the presence or quantity of Parabacteroides bacteria is acquired from the intestinal flora information, and in the food information deriving step, information on the food is derived based on the information on the presence or quantity of Parabacteroides bacteria, wherein the food is a composition comprising any one selected from the group consisting of trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these as constituent sugars. Alternatively, in the information acquisition step, information on the presence or quantity of Bifidobacterium bacteria is acquired from the intestinal flora information, and in the food information deriving step, information on the food is derived based on the information on the presence or quantity of Bifidobacterium bacteria, wherein the food is a composition comprising trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these as constituent sugars.

[0202] The method may further include: displaying the provided food information on a terminal of the target. The terminal of the target may be, for example, a tablet terminal, a smart phone, or a personal computer.

[0203] Hereinafter, the present invention will be further described in detail using examples, but the technical scope of the present invention is not limited to these examples.

[0204] [Example]

[0205] [Test Example 1]

[0206] (Stool Culture)

[0207] Each evaluation substance was added to a stool dilution prepared by suspending stool from a healthy adult in a semi-fluidized medium for GAM sugar decomposition "Nissui" (Nissui Pharmaceutical Co., Ltd.) from which agar had been removed by filtration, at a concentration of 0.25% (n=4).

[0208] Four sets of feces were tested separately without mixing. The culture medium used in the test was allowed to stand in an anaerobic glove box for at least one night before use. The cultures were cultured in a 96-well deep-well plate at 37°C in an anaerobic environment for one day. The cultured bacterial flora was compared with a control condition in which distilled water was added instead of the following evaluation substances to evaluate the prebiotic function of the added evaluation substances.

[0209] As evaluation substances, the following were used.

[0210] Isomaltulose (Palatinose (registered trademark)): Fujifilm Wako Pure Chemical Industries, Ltd. "Palatinose Monohydrate" No.: 169-12991

[0211] Turabiose: Toronto Research Chemicals,

[0212] "3-OaD-Glucopyranosyl-D-fructose" No.: G423500

[0213] Maltulose: COSMO BIO, "Maltulose Monohydrate," No. SC-295372 Trehalulose: Carbosynth, "Trehalulose," No. OT09774

[0214] (Analysis of intestinal bacterial occupancy using next-generation sequencing)

[0215] 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 resulting .fastq file was then processed by

[0216] QIIME2 (https: / / qiime2.org / ) was used for analysis, and the occupancy rate of each intestinal bacteria was calculated.

[0217] The results are shown in Figure 1 and Figure 2 For each of the evaluated substances, an increase in the occupancy rate of Bifidobacterium and Parabacteroides was observed. Furthermore, in the systems where each of the evaluated substances was added, changes in the occupancy rate of various bacteria were observed in the overall bacterial flora, indicating an impact on the symbiotic relationship between bacteria.

[0218] [summary]

[0219] Parabacteroides bacteria are bacteria that live in the intestines. By promoting the proliferation of Parabacteroides bacteria, it is expected to have an effect on inflammation, obesity, glucose metabolism disorders, fatty liver and cancer (non-patent literature 1 to 3). In addition, it is reported that: Parabacteroides dieldii is reduced in patients with multiple sclerosis (MS) (non-patent literature 4), and a combination of Parabacteroides bacteria, Oscillospira bacteria, Rikenaceae bacteria, Parabacteroides bacteria, etc. can distinguish patients with non-alcoholic fatty liver disease (NAFLD) from healthy controls (CTRLs) (non-patent literature 5). Therefore, by Figure 1 Trehalulose, isomaltulose, turanose, maltulose, and oligosaccharides containing any of these as constituent sugars are considered to be useful for treating any of the group consisting of inflammation, obesity, glucose metabolism disorders, multiple sclerosis (MS), fatty liver, and cancer.

[0220] It was also reported that oral administration of Parabacteroides goldsteinii improved weight loss and the increase of inflammatory cytokines in lung tissue in mice with chronic obstructive pulmonary disease (COPD) induced by smoking. As a mechanism, it was suggested that pentaacyl lipopolysaccharide, a cell wall component of Parabacteroides goldsteinii, antagonized the activation of TLR4 receptors caused by inflammatory hexaacyl lipopolysaccharide from intestinal bacteria (Non-Patent Document 6). Figure 1 Trehalulose, isomaltulose, turanose, maltulose, and oligosaccharides containing any of these as constituent sugars are considered to be useful for treating chronic obstructive pulmonary disease (COPD).

[0221] Regarding Bifidobacterium bacteria, it was also observed that the occupancy rate increased in the case of all the evaluated substances, trehalulose, isomaltulose, turanose, and maltulose ( Figure 2 ).

[0222] It is known that bifidobacteria themselves or the short-chain fatty acids produced by bifidobacteria have an intestinal conditioning effect, and when short-chain fatty acids are produced, the pH in the large intestine decreases, resulting in an increase in the solubility of minerals, which makes it easier to pass through mucosal cells and promote their absorption by cells (Non-Patent Document 7). Figure 2 Trehalulose, isomaltulose, turanose, and maltulose, as well as oligosaccharides containing any of these as constituent sugars, are believed to be useful for conditioning the intestinal tract and promoting the absorption of minerals. Examples of minerals include calcium, magnesium, iron, potassium, zinc, copper, chromium, manganese, molybdenum, iodine, sodium, phosphorus, and selenium. The composition is expected to promote the absorption of calcium, magnesium, and iron, in particular.

[0223] [Production Example 1: Production of Composition Using Sucrose]

[0224] (Preparation of Enzyme Solution)

[0225] Lactobacillus ruberulosa JCM12392 activated and cultured in commercially available MRS liquid medium was transplanted at 1% into the medium shown below. The culture was maintained at a constant pH of 6.4 with sodium hydroxide in a small jar fermentor at 30°C for 27 hours, and then cooled to below 10°C to terminate the culture. The resulting culture solution was centrifuged, and the supernatant discarded. The resulting Lactobacillus ruberulosa concentrate, which had a 15-fold bacterial concentration, was used as an enzyme solution.

[0226]

Table 2

[0227]

[0228] (Enzyme reaction)

[0229] Sucrose 65 w / w% and enzyme solution 0.5 w / w% were mixed and reacted at 48°C for 24 hours under static conditions. The sugar composition after the reaction was analyzed by LCMS using an amide column (BEH Amide, Waters) as shown in the figure. Figure 3 The composition contains leucrose, isomaltulose, trehalulose, and the like. The table below shows the results of pretreatment using a GC solid phase column and quantitative evaluation using three types of HPLC systems (NH2 column, Na ligand exchange column, and aqueous connection column) (concentration w / w % in the reaction composition (liquid, solid content 65 w / w %)).

[0230]

Table 3

[0231]

[0232] (summary)

[0233] A composition containing leucrose was produced by allowing Lactobacillus rhodostripe JCM12392, which produces the bacterial-bound glucansucrase, to act on a composition containing sucrose. The produced composition contained leucrose, isomaltulose, trehalulose, kojibiose, and isomaltulose in addition to leucrose. Furthermore, turanose and maltulose may also be present.

[0234] Industrial applicability

[0235] The present invention supports the maintenance and improvement of human health through a composition for improving intestinal flora, comprising any of trehalulose, isomaltulose, turanose, and maltulose, as well as oligosaccharides containing any of these as constituent sugars. Furthermore, the present invention can provide a food composition and a method for producing a food that supports the maintenance and improvement of human health. Furthermore, the present invention can improve the nutritional needs of various individuals, ensuring healthy living and promoting well-being.

[0236] [Sequences listed in the sequence listing]

[0237] SEQ ID NO: 1-8: Amino acid sequence of glycoside hydrolase

[0238] SEQ ID NO: 9-21: Amino acid sequence of glycoside hydrolase (partial)

Claims

1. Use of any one selected from trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these as constituent sugars, in the production of a composition for suppressing the growth of bacteria belonging to the genus Parabacteroides.

2. The use according to claim 1, which is used to promote the proliferation of bacteria of the genus Bifidobacterium.

3. The use according to claim 1, used as a prebiotic or synbiotic.

4. Use of any one of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars, for the non-therapeutic treatment of any one of the group consisting of inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorder, multiple sclerosis, fatty liver and cancer.

5. The use according to claim 4, wherein The treatment works by promoting the proliferation of Parabacteroides bacteria in the intestine.

6. Use of any of the oligosaccharides selected from trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars, for non-therapeutic treatment of a disease or condition that is ameliorated by promoting the growth of Parabacteroides bacteria in the intestine.

7. The use according to claim 1, wherein The genus Parabacteroides includes Parabacteroides distasonis.

8. Use of a composition for controlling the growth of bacteria belonging to the genus Bifidobacterium comprising any one of trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these as constituent sugars.

9. Use of any of trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars, for promoting mineral absorption and regulating the intestinal tract.

10. The use according to claim 9, which is based on promoting the proliferation of Bifidobacterium bacteria in the intestine.

11. Use of any oligosaccharide selected from trehalulose, isomaltulose, turanose, and maltulose, and any of these oligosaccharides as constituent sugars, for non-therapeutic treatment of a disease or condition that is ameliorated by promoting the growth of Bifidobacterium bacteria in the intestine.

12. The use according to any one of claims 1 to 11, wherein The composition for suppressing the growth of bacteria of the genus Parabacteroides contains any one selected from trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these as constituent sugars, in the form of a composition containing any one of trehalulose and isomaltulose obtained by allowing dextran sucrase to act on a composition containing sucrose.

13. The use according to claim 11, wherein Glucan sucrase is produced from lactic acid bacteria or a processed product thereof.

14. A method for producing any one selected from trehalulose and isomaltulose, and oligosaccharides containing any one of these as constituent sugars, characterized in that: Glucansucrase is allowed to act on a composition comprising sucrose.

15. The manufacturing method according to claim 14, wherein: Glucan sucrase is produced from lactic acid bacteria or a processed product thereof.

16. The manufacturing method according to claim 15, wherein: Glucansucrase is used in the form of lactic acid bacteria expressing Glucansucrase, and is a bacteria-bound type.

17. The manufacturing method according to claim 15 or 16, wherein: The lactic acid bacteria is red-striped liquid lactobacillus (Liquorilactobacillus satsumensis).

18. A food information providing device comprising: an information acquisition unit, for acquiring information about the intestinal flora of the subject; an deriving unit for deriving information of food provided to the subject based on the information of the intestinal flora; as well as a providing unit, providing the derived food information to the object, The information acquisition unit acquires information on the presence or quantity of Parabacteroides bacteria or Bifidobacterium bacteria from information on the intestinal flora, and the derivation unit derives information on the food based on the information on the presence or quantity of Parabacteroides bacteria or Bifidobacterium bacteria, wherein the food is a composition containing any one selected from trehalulose, isomaltulose, turanose and maltulose, and oligosaccharides containing any of these as constituent sugars.

19. The device according to claim 18, wherein The provided food information can be displayed on the subject's terminal.

20. The apparatus according to claim 18 or 19, further comprising a display unit for displaying the provided food information.

21. A method for providing food information, comprising the following steps: obtaining information about the subject's intestinal flora; Based on the information about the intestinal flora, information about the food provided to the subject is derived; then providing the derived food information to the subject, In the information acquisition step, information on the presence or quantity of Parabacteroides bacteria or Bifidobacterium bacteria is acquired from the intestinal flora information, and in the food information deriving step, food information is derived based on the information on the presence or quantity of Parabacteroides bacteria or Bifidobacterium bacteria, wherein the food is a composition comprising any one selected from trehalulose, isomaltulose, turanose, and maltulose, and oligosaccharides containing any of these as constituent sugars.

22. The method according to claim 21, further comprising the step of displaying the provided food information on a terminal of the subject.

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