Composition for improving intestinal microbiota

Abstract

To provide a composition for improving intestinal microbiota and a method for producing the same.SOLUTION: A composition for improving intestinal microbiota comprises at least one selected from leucrose and an oligosaccharide comprising leucrose as a constituent sugar, wherein the improvement of intestinal microbiota includes promotion of growth of bacteria belonging to the genus Parabacteroides or the genus Bifidobacterium.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] The present invention relates to a composition for improving intestinal flora. [Background technology]

[0002] In recent years, intestinal barrier dysfunction, known as leaky gut, caused by lifestyle habits and stress, has become a problem. Inflammation caused by leaky gut allows harmful substances to spread throughout the body via the blood vessels, and it has been suggested that this is involved not only in intestinal inflammation but also in the onset and progression of lifestyle-related diseases such as obesity and diabetes. Improving the intestinal flora is being considered as one way to improve leaky gut.

[0003] Parabacteroides bacteria are a type of bacteria that inhabit the intestine. Regarding Parabacteroides bacteria, for example, Non-Patent Document 1 investigates the possibility that an isolated fraction containing Hirsutella sinensis mycelium (HSM) and polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the intestinal microbiota. This document reports that a specific fraction selectively promotes the growth of Parabacteroides goldsteinii, a resident bacterium whose levels were reduced in mice fed a high-fat diet (HFD). Furthermore, oral administration of live P. goldsteinii to HFD-fed mice reduced obesity and was associated with increased adipose tissue thermogenesis, improved intestinal health, and reduced levels of inflammation and insulin resistance. Furthermore, Non-Patent Document 2 investigates the metabolic effects of Parabacteroides distasonis (PD) on reducing weight gain, hyperglycemia, and hepatic steatosis in HFD-fed mice. This paper reports that administration of P. distasonis to HFD-fed mice resulted in increased lithocholic acid and ursodeoxycholic acid, dramatic changes in bile acid profiles, and elevated intestinal succinic acid levels. Furthermore, Non-Patent Document 3 reports that P. distasonis membrane fraction (PdMb) strongly suppressed the production of inflammatory cytokines and reduced the expression of MyD88 and pAkt (ser473) induced by E. coli lipopolysaccharide in colon cancer cell lines. Furthermore, PdMb induced apoptosis in colon cancer cell lines and inhibited TLR4 activation in reporter cells. This paper states that these results suggest that P. distasonis has anti-inflammatory and anti-cancer effects, likely mediated by the suppression of TLR4 and Akt signaling and the promotion of apoptosis.

[0004] Furthermore, Non-Patent Document 4 mentions that P. distasonis is reduced in multiple sclerosis (MS) patients, and Non-Patent Document 5 reports that multivariate analysis shows that a combination of Oscillospira, Rickenellaceae, and Parabacteroides bacteria can distinguish non-alcoholic fatty liver disease (NAFLD) patients from healthy controls (CTRLs). Non-Patent Document 6 reports that oral administration of Parabacteroides goldsteinii improved weight loss and elevated inflammatory cytokines in lung tissue in a mouse model of smoking-induced chronic obstructive pulmonary disease (COPD). This document also suggests that the mechanism is that pentaacyl lipopolysaccharide, a cell wall component of Parabacteroides goldsteinii, antagonizes the activation of the TLR4 receptor by inflammatory hexaacyl lipopolysaccharide derived from intestinal bacteria.

[0005] On the other hand, leucrose is known to have several functions. For example, Patent Document 1 describes a mixture containing L-carnitine and at least one low-glycemic sucrose isomer, where the low-glycemic sucrose isomer is isomaltulose or leucrose, and the mixture contains 80 to 99.9 wt. % of the low-glycemic sucrose isomer (based on the total dry matter of the mixture). Patent Document 2 also describes the use of a low-glycemic food composition for the production of a functional food for the treatment and / or prevention of malignant tumor diseases in humans or animals, and describes that the food composition contains isomaltulose, leucrose, trehalulose, and / or turanose as a low-glycemic carbohydrate source, alone or in combination with a sugar alcohol, inulin, polydextrose, and / or resistant starch.

[0006] On the other hand, fructooligosaccharides are used as ingredients in foods for specified health uses, and their ingestion is known to increase bifidobacteria present in the large intestine, and the proliferation of bifidobacteria itself, or the action of short-chain fatty acids produced by bifidobacteria, is known to exert an intestinal regulating effect. It is also known that the production of short-chain fatty acids decreases the pH in the large intestine, thereby increasing the solubility of minerals, making them easier to pass through mucosal cells and facilitating their absorption into the cells (Non-Patent Document 7). [Prior art documents] [Patent documents]

[0007] [Patent Document 1] WO2007 / 009742 (Patent No. 4554708) [Patent Document 2] WO2007 / 107295 (Special Publication No. 2009-530326) [Non-patent literature]

[0008] [Non-Patent Document 1] Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis. Gut. 2019 Feb;68(2):248-262 [Non-patent document 2] Parabacteolides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bile acids. Cell Rep. 2019 Jan 2;26(1):222-235 [Non-patent document 3] Parabacteroides distasonis attenuates toll-like receptor 4 signaling and Akt activation and blocks coon tumor formation in high-fat diet-fed azoxymethane-treated mice. Koh et al., Int. J. Cancer. 2018;143(7):1797-1805 [Non-patent document 4] Gut bacteria from multiple sclerosis patients modulate human T cells and worsening symptoms in mouse models. Cekanaviciute et al., Proc. Natl. Acad. Sci. USA. 2017;114(70):10713-10718 [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 [Non-patent document 6] Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide. Gut microbiota 2022;71, [Non-Patent Document 7] The mineral absorption-promoting effect of indigestible carbohydrates (fructooligosaccharides). Journal of the Japanese Society of Nutrition and Food Science, Vol. 52, No. 6, 387-395 Summary of the Invention [Problem to be solved by the invention]

[0009] Parabacteroides bacteria are considered to be one of the beneficial intestinal bacteria. However, Parabacteroides bacteria are not a common species of probiotic, and there is little experience of their use in food. Therefore, the safety and gastrointestinal transit of oral intake of compositions containing Parabacteroides bacteria are unknown. Furthermore, bifidobacteria do not easily reach the intestine even when orally ingested. Increasing the occupancy rate of these bacteria in the intestinal flora using specific prebiotics is considered to be a practically useful method. [Means for solving the problem]

[0010] The present invention provides: [1] A composition for improving the intestinal flora, comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar. [2] The composition described in 1, wherein the improvement of the intestinal flora includes promoting the growth of Parabacteroides bacteria. [3] The composition described in 1 or 2, wherein the improvement of the intestinal flora includes promoting the growth of bacteria of the genus Bifidobacterium. [4] A composition described in any one of 1 to 3 for use as a prebiotic or synbiotic. [5] A composition for treating any of inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorders, multiple sclerosis, hepatic steatosis, and cancer, comprising any of leucrose and oligosaccharides having leucrose as a constituent sugar. [6] The composition described in 5, wherein the treatment is by promoting the growth of Parabacteroides bacteria in the intestine. [7] A composition for treating a disease or condition that is improved by promoting the growth of Parabacteroides bacteria in the intestine, comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar. [8] A composition for promoting mineral absorption and regulating the intestines, comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar. [9] The composition described in 8, which promotes the growth of Bifidobacterium bacteria in the intestines.

[10] A composition for treating a disease or condition that is improved by promoting the growth of Bifidobacterium bacteria in the intestines, comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar.

[11] A composition described in any one of 1 to 10, which contains one selected from leucrose and oligosaccharides having leucrose as a constituent sugar, as a composition containing leucrose and oligosaccharides having leucrose as a constituent sugar, obtained by acting glucansucrase on a composition containing sucrose.

[12] The composition described in any one of 1 to 11, wherein the composition comprises any one selected from isomaltulose, kojibiose, trehalulose, and isomaltose.

[13] The composition described in 11 or 12, wherein the glucansucrase is a lactic acid bacterium or a processed product thereof.

[14] A method for producing a composition containing leucrose, characterized by allowing a cell-bound glucansucrase to act on a composition containing sucrose.

[15] The method according to 14, wherein the glucansucrase is derived from lactic acid bacteria.

[16] The method according to 14 or 15, wherein glucansucrase is used as a lactic acid bacterium expressing glucansucrase.

[17] The method according to any one of items 13 to 16, wherein the lactic acid bacterium is Liquorilactobacillus satsumensis.

[18] An information acquisition section that acquires information on the subject's intestinal microbiota; A derivation unit that derives information about food to be provided to the subject based on information about the intestinal microbiota; and A provision section that provides the derived food information to the target Equipped with A food information providing device in which an information acquisition unit acquires information on the presence or amount of Parabacteroides bacteria or Bifidobacterium bacteria from information on the intestinal flora, and a derivation unit derives information on foods that are compositions containing either leucrose or oligosaccharides having leucrose as a constituent sugar based on the information on the presence or amount of Parabacteroides bacteria.

[19] The device described in 18, wherein the food information provided can be displayed on the target terminal.

[20] The device described in 18 or 19, further comprising a display unit that displays information about the food to be provided.

[21] to obtain information on the subject's gut microbiota; Deriving information about the foods to be provided to the subject based on the information about the intestinal microbiota; and Provide the derived food information to the target The process includes the steps of: A food information providing method in which, in the information acquisition step, information on the presence or amount of Parabacteroides bacteria or Bifidobacterium bacteria is acquired from information on the intestinal flora, and, in the food information deriving step, information on a food that is a composition containing any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar is derived based on the information on the presence or amount of Parabacteroides bacteria.

[22] The method according to 21, further comprising the step of displaying the provided food information on the target terminal.

[0011]

[31] A composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar, for use in a method for improving intestinal flora. Use of any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar in the manufacture of a composition for improving intestinal flora. A method or non-therapeutic method for improving intestinal flora, comprising the step of administering to a subject a composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar. Use or non-therapeutic use of a composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar for improving intestinal flora.

[32] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to 31, wherein the improvement of the intestinal flora includes promoting the growth of Parabacteroides bacteria.

[33] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to 31 or 32, wherein the improvement of the intestinal flora includes promoting the growth of Bifidobacterium bacteria.

[34] The composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use of any one of claims 31 to 33, wherein the composition is for use as a prebiotic or synbiotic.

[35] A composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent saccharide, for use in a method for treating any one selected from inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorders, multiple sclerosis, hepatic steatosis, and cancer. Use of any one selected from leucrose and oligosaccharides having leucrose as a constituent saccharide in the manufacture of a composition for treating any one selected from inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorders, multiple sclerosis, hepatic steatosis, and cancer. A method or non-therapeutic method for treating any one selected from inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorders, multiple sclerosis, hepatic steatosis, and cancer, comprising the step of administering to a subject a composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent saccharide. Use or non-therapeutic use of a composition containing any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar for the treatment of any one selected from inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorders, multiple sclerosis, hepatic steatosis, and cancer.

[36] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to 35, wherein the treatment is by promoting the growth of Parabacteroides bacteria in the intestine.

[37] A composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent saccharide, for use in a method for treating a disease or condition that is ameliorated by promoting the growth of Parabacteroides bacteria in the intestine. Use of any one selected from leucrose and oligosaccharides having leucrose as a constituent saccharide in the manufacture of a composition for treating a disease or condition that is ameliorated by promoting the growth of Parabacteroides bacteria in the intestine. A method or non-therapeutic method for treating a disease or condition that is ameliorated by promoting the growth of Parabacteroides bacteria in the intestine, comprising the step of administering to a subject a composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent saccharide. Use or non-therapeutic use of a composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent saccharide for treating a disease or condition that is ameliorated by promoting the growth of Parabacteroides bacteria in the intestine.

[38] A composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar, for use in a method for either promoting mineral absorption or regulating intestinal function. Use of any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar in the manufacture of a composition for either promoting mineral absorption or regulating intestinal function. A method or non-therapeutic method for either promoting mineral absorption or regulating intestinal function, comprising the step of administering to a subject a composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar. Use or non-therapeutic use of a composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar for either promoting mineral absorption or regulating intestinal function.

[39] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to 38, by promoting the growth of Bifidobacterium bacteria in the intestine.

[40] A composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar, for use in a method for treating a disease or condition that is ameliorated by promoting the growth of bacteria of the genus Bifidobacterium in the intestine. Use of any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar in the manufacture of a composition for treating a disease or condition that is ameliorated by promoting the growth of bacteria of the genus Bifidobacterium in the intestine. A method or non-therapeutic method for treating a disease or condition that is ameliorated by promoting the growth of bacteria of the genus Bifidobacterium in the intestine, comprising the step of administering to a subject a composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar. Use of a composition comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar in the treatment of a disease or condition that is ameliorated by promoting the growth of bacteria of the genus Bifidobacterium in the intestine.

[41] A composition, use in production, method or non-therapeutic method, or use or non-therapeutic use described in any one of items 31 to 40, comprising a composition containing leucrose and an oligosaccharide having leucrose as a constituent sugar, which is obtained by acting glucansucrase on a composition containing sucrose.

[42] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use of any one of items 31 to 41, wherein the composition comprises any one selected from isomaltulose, kojibiose, trehalulose, and isomaltose.

[43] The composition, use in production, method or non-therapeutic method, or use or non-therapeutic use according to 41 or 42, wherein the glucansucrase is a lactic acid bacterium or a processed product thereof. [Effects of the Invention]

[0012] The present invention can improve the intestinal bacterial flora, and in particular, can promote the increase of bacteria of the genus Parabacteroides and bacteria of the genus Bifidobacterium in the intestinal bacterial flora. By promoting the proliferation of Parabacteroides bacteria in the intestinal flora, it is possible to treat any of inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorders, multiple sclerosis, hepatic steatosis, and cancer, and it is expected that promoting the proliferation of Parabacteroides bacteria and Bifidobacterium bacteria in the intestinal flora will enable the treatment of various diseases or conditions. By adding the active ingredient of the present invention, functional foods in various forms can be provided. [Brief explanation of the drawings]

[0013] [Figure 1] Changes in the occupancy rate of Parabacteroides bacteria in Ruminococcus-type human fecal culture systems with various carbohydrates. [Figure 2] Changes in the occupancy rate of Parabacteroides bacteria in a Bacteroides-type human fecal culture system using various carbohydrates. [Figure 3] Changes in the occupancy rate of Parabacteroides bacteria in Prevotella-type human fecal culture systems with various carbohydrates. [Figure 4] Changes in the occupancy rate of Bifidobacterium and Parabacteroides bacteria by leucrose in a mixed culture system of human feces from four individuals. [Figure 5] 65 w / w% sucrose and 0.5 w / w% enzyme solution (Lactobacillus satsumensis JCM12392) were mixed and reacted at 48°C for 24 hours under static conditions, and then the sugar composition was analyzed by LCMS. [Figure 6]

[0023] Figure 1 shows the amino acid sequence of a glucansucrase used in one embodiment. The underlined parts indicate the important sites for the desired enzymatic activity. [Figure 7] Amino acid sequence of glucansucrase used in one embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0014] This embodiment relates to a composition for improving the intestinal bacterial flora, which contains leucrose and an oligosaccharide containing leucrose as a constituent sugar as an active ingredient.

[0015] [Active ingredient] The composition of this embodiment contains, as an active ingredient, either leucrose or an oligosaccharide containing leucrose as a constituent sugar. In the context of the present invention, reference to an oligosaccharide containing leucrose as a constituent sugar does not include leucrose itself. In the context of the present invention, the term "either" is used to mean "at least one" unless otherwise specified. For example, "either leucrose or an oligosaccharide containing leucrose as a constituent sugar" includes cases where there is only leucrose, only one type of oligosaccharide containing leucrose as a constituent sugar, leucrose and one type of oligosaccharide containing leucrose as a constituent sugar, and two types of oligosaccharides containing leucrose as a constituent sugar.

[0016] The leucrose and oligosaccharides containing leucrose as a constituent sugar used in the composition are not particularly limited as long as they have the desired effect. Furthermore, the leucrose and oligosaccharides containing leucrose as a constituent sugar used in the composition may be one type or a combination of two or more types.

[0017] Examples of oligosaccharides containing leucrose as a constituent sugar include those in which 1 to 7, preferably 2 to 6, more preferably 3 to 4, and even more preferably 1 to 2 monosaccharides are bound to leucrose. A specific example is α-D-Glcp-(1→6)-α-D-Glcp-(1→5)-D-Fru, in which one glucose molecule is bound to the glucose at the non-reducing end of leucrose.

[0018] In a preferred embodiment, the composition comprises leucrose.

[0019] Oligosaccharides containing leucrose as a constituent sugar can produce leucrose in the digestive tract of a subject after administration to the subject, and therefore, oligosaccharides containing leucrose as a constituent sugar can have the same effect on the intestinal flora as leucrose.

[0020] The origin and production method of the leucrose and oligosaccharides containing leucrose as a constituent sugar used in this embodiment are not particularly limited, and they may be produced by any method, such as fermentation, enzymatic methods, or organic synthesis. An example of a production method includes a step of treating a composition containing sucrose with glucansucrase, or lactic acid bacteria expressing glucansucrase, or a processed product thereof, to obtain a composition containing galactosyl kojibiose. In the present invention, glucansucrase refers to an enzyme belonging to glycoside hydrolase (also known as glycosyl hydrolases) family 70 (GH70), unless otherwise specified (see (CAZy) databases and Cantarel et al., Nucleic Acids Res. 37:D233-238, 2009).

[0021] An example of the glucansucrase used in this embodiment is a glucansucrase consisting of the following proteins (A), (B), or (C): The glucansucrase consisting of the following proteins (A), (B), or (C) may be in the form of a lactic acid bacterium that expresses glucansucrase or a processed product thereof, and in such cases, it can be said that the glucansucrase is used in the production method of this embodiment.

[0022] (A) A protein consisting of an amino acid sequence set forth 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 set forth 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 have been substituted, deleted, inserted, and / or added in the amino acid sequence set forth in any one of SEQ ID NOs: 1 to 8 and having glucansucrase activity.

[0023] In one aspect, the glucansucrase consists of a protein of (B') or (C') below: (B') a protein having glucansucrase activity, which has an amino acid sequence highly identical to the amino acid sequences set forth in SEQ ID NOs: 1 to 8, with the exception that the portions corresponding to positions 450-467, 488-499, and 559-573 of SEQ ID NO: 1 are identical; (C') a protein having glucansucrase activity, which has an amino acid sequence set forth in SEQ ID NOs: 1 to 8, with the exception that the portions corresponding to positions 450-467, 488-499, and 559-573 of SEQ ID NO: 1 are identical.

[0024] The amino acid sequence of GTF21, a cell-associated, constitutively expressed glucansucrase derived from Liquorilactobacillus satsumensis, is shown in SEQ ID NO: 1. In this sequence, positions 450-467, 488-499, and 559-573 are known to be important for glucansucrase activity (J. Agric. Food Chem. 2011, 59, 4148-4155).

[0025] SEQ ID NOs: 2-4 show the amino acid sequences of glucansucrase (GTF68, GTF29, and GFT39, respectively) found in L. satsumensis that has a sequence other than that of SEQ ID NO: 1. SEQ ID NO: 5 shows the amino acid sequence of glucansucrase found in Leuconostoc meseteroides (accession number AAB40875). SEQ ID NO: 6 shows the amino acid sequence of glucansucrase found in Leuconostoc citreum (accession number ACY92456). SEQ ID NO: 7 shows the amino acid sequence of glucansucrase found in Streptococcus mutans (accession number AAN58705). SEQ ID NO: 8 shows the amino acid sequence of glucansucrase found in Limosilactobacillus reuteri (accession number AAU08001).

[0026] The sequence identity between each sequence and the amino acid sequence of SEQ ID NO: 1 is shown below and in Figure 7. These values ​​were calculated by comparative analysis of protein amino acid sequences (BLASTP) using the BLAST algorithm provided by NCBI (National Center for Biotechnology Information) (http: / / www.ncbi.nlm.nih.gov / BLAST / ). SEQ ID NO: 2: 49%, SEQ ID NO: 3: 62%, SEQ ID NO: 4: 48%, SEQ ID NO: 5: 46%, SEQ ID NO: 6: 45%, SEQ ID NO: 7: 47%, SEQ ID NO: 8: 56%.

[0027] The portion of positions 559-573 in SEQ ID NO: 1 corresponds to conserved sequence 4 in Non-Patent Document 7. In one aspect, the glucansucrase used consists of the protein (B) or (C). In this case, regardless of the sequence of other portions, the glucansucrase has one or more, preferably two or more, more preferably three or more, and even more preferably all, selected from the amino acid (H) corresponding to position 565 in SEQ ID NO: 1, the amino acid (D) corresponding to position 566 in SEQ ID NO: 1, the amino acid (S) corresponding to position 567 in SEQ ID NO: 1, the amino acid (D) corresponding to position 571 in SEQ ID NO: 1, and the amino acid (Q) corresponding to position 572 in SEQ ID NO: 1, identical to SEQ ID NO: 1. Positions 566-567 and 571-572 in SEQ ID NO: 1 are important as recognition sites for the acceptor (lactose in this embodiment) (Non-Patent Document 7). Positions 565-566 in SEQ ID NO: 1 are highly conserved among glucansucrases.

[0028] The portion of positions 488-499 in SEQ ID NO: 1 corresponds to conserved sequence 3 in Non-Patent Document 7. In one aspect, the glucansucrase used consists of protein (B) or (C), and in this case, regardless of the sequence of other portions, the glucansucrase has one or more, preferably two or more, more preferably three or more, and even more preferably all, selected from positions 488 to 493 (HLSILE) of SEQ ID NO: 1 that are identical to SEQ ID NO: 1. In a particularly preferred aspect, regardless of the sequence of other portions, the amino acid (H) corresponding to position 488 of SEQ ID NO: 1 and the amino acid (E) corresponding to the position in SEQ ID NO: 1 are identical.

[0029] The portion of SEQ ID NO: 1 at positions 450-467 corresponds to conserved sequence 2 in Non-Patent Document 7. In one aspect, the glucansucrase used consists of protein (B) or (C), in which the glucansucrase has one or more, preferably two or more, more preferably three or more, and even more preferably all, selected from the amino acid (R) corresponding to position 453 of SEQ ID NO: 1, the amino acid (D) corresponding to position 455 of SEQ ID NO: 1, the amino acid (A) corresponding to position 456 of SEQ ID NO: 1, and the amino acid (D) corresponding to position 458 of SEQ ID NO: 1, regardless of the sequences of other portions.

[0030] [Table 1]

[0031] The glucansucrase used is preferably an enzyme having the activity of catalyzing the reaction of breaking down sucrose into glucose and fructose and the reaction of adding glucose to a glucan chain, and is preferably an enzyme having any activity selected from the group consisting of dextransucrase (EC 2.4.1.5) activity, alternansucrase (EC 2.4.1.140) activity, reuteransucrase (EC 2.4.1.-) activity, α-4,6-glucanotransferase (EC 2.4.1.-) activity, α-1,2-branched dextransucrase (EC 2.4.1.-) activity, α-4,3-glucanotransferase (EC 2.4.1.-) activity, and mutansucrase (EC 2.4.1.372) activity, and more preferably one having at least dextransucrase (EC 2.4.1.5) activity.

[0032] In the present invention, whether a protein has glucansucrase activity can be determined by determining whether the protein has dextransucrase (EC 2.4.1.5) activity, alternansucrase (EC 2.4.1.140) activity, reuteransucrase (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. It is more preferable to determine whether a protein has glucansucrase activity by determining whether the protein has dextransucrase (EC 2.4.1.5) activity.

[0048] With respect to the amino acid sequence of glucansucrase, high sequence identity means that the identity value is 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, even more preferably 90% or more, even more preferably 95% or more, and even more preferably 98% or more.

[0033] In the present invention, the term "identity" in reference to amino acid sequences refers to the percentage of identical amino acids shared between two sequences when the two sequences are aligned in an optimal manner, unless otherwise specified. Searches and analyses of amino acid sequence identity can be performed using algorithms or programs well known to those skilled in the art, such as GENETIX (registered trademark) ver. 14 (Genetics Corporation), BLASTN, BLASTP, BLASTX, and ClustalW. When using a program, parameters can be appropriately set by those skilled in the art, or the default parameters of each program may be used. Specific techniques for these analysis methods are also well known to those skilled in the art.

[0034] In the present invention, when referring to an amino acid sequence in which one or more amino acids have been substituted, deleted, inserted, and / or added, the number of substituted amino acids is not particularly limited, unless otherwise specified, as long as the protein comprising that amino acid sequence has the desired activity. However, in the case of a glucansucrase comprising the sequence of SEQ ID NO: 1, which consists of a full-length 1075 amino acid sequence, the number of substituted amino acids is, for example, less than 50% (specifically, 537 or fewer), preferably 37% or fewer (specifically, 409 or fewer), more preferably 200 or fewer, even more preferably 100 or fewer, even more preferably 50 or fewer, even more preferably 20 or fewer, and even more preferably 1 to 9. Substitutions with amino acids having similar properties may also be possible. Means for preparing polynucleotides or proteins comprising such amino acid sequences are well known to those skilled in the art.

[0035] In the present invention, in a certain amino acid sequence S, the amino acid corresponding to position x (xth position from the N-terminus) of a reference sequence (e.g., SEQ ID NO: 1) refers to the amino acid that corresponds to the amino acid at position x in the reference sequence in sequence S when sequence S and the reference sequence are aligned. If sequence S is a reference sequence in which one or more amino acids have been deleted, the position of this corresponding amino acid in sequence S may be shifted from the reference sequence and may not be at position x in sequence S. Those skilled in the art can appropriately determine which amino acid in sequence S corresponds to the amino acid at position x in the reference sequence.

[0036] When lactic acid bacteria are used, they are preferably lactic acid bacteria that express glucansucrase. Preferred examples of lactic acid bacteria include lactic acid bacteria belonging to the family Leuconostoc, more preferably those belonging to the genus Leuconostoc, and even more preferably Leuconostoc mesenteroides. When lactic acid bacteria are used, they are preferably lactic acid bacteria that stably express glucansucrase. Preferred examples of lactic acid bacteria include those belonging to the Lactobacillaceae family, more preferably those belonging to the genus Liquorilactobacillus or Limosilactobacillus, and even more preferably Limosilactobacillus reuteri or Liquorilactobacillus satsumensis.

[0037] When lactic acid bacteria are used, they are preferably lactic acid bacteria that constantly express glucansucrase, and more preferably the glucansucrase is cell-associated. Preferred examples of lactic acid bacteria include lactic acid bacteria belonging to the family Lactobacillaceae, more preferably lactic acid bacteria belonging to the genus Liquorilactobacillus, and even more preferably Liquorilactobacillus satsumensis. A particularly preferred example of a Liquorilactobacillus satsumensis strain is JCM12392. JCM12392 is referred to as Lactobacillus satsumensis in the RIKEN BioResource Center, GENERAL CATALOG No. 9, 2012, JAPAN COLLECTION OF MICROORGANISMS, M51.

[0038] In addition, when describing lactic acid bacteria in relation to the present invention, unless otherwise specified, the classification follows the reclassification by Zheng J, Wittouck S, Salvetti E, Franz CMAP, Harris HMB, Mattarelli P, O'Toole PW, Pot B, Vandamme P, Walter J, Watanabe K, Wuyts S, Felis GE, Ganzle MG, Lebeer S.: A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol. 2020 Apr; 70(4): 2782-2858. According to the classification before the reorganization, Liquorilactobacillus satsumensis is classified as Lactobacillus satsumensis.

[0039] The lactic acid bacteria that express glucansucrase or a processed product thereof is preferably any one selected from the group consisting of live cells, dead cells, a culture containing cells, crushed cells, a concentrated culture, a dried culture, a granulated culture, a crushed cell solution, a dried crushed cell solution, a granulated crushed cell solution, and a purified product of glucansucrase.

[0040] Glucansucrase, or a lactic acid bacterium expressing glucansucrase, or a processed product thereof, used for producing leucrose and oligosaccharides containing leucrose as a constituent sugar, They can be produced using transformation, chemical synthesis, or genome editing techniques.

[0041] The leucrose-containing composition obtained by such a production method can be used as is as a solution containing leucrose and oligosaccharides whose constituent sugars are leucrose, or can be used after purification using an ion exchange resin, etc. That is, the composition of this embodiment may be a leucrose-containing composition obtained by treating a composition containing sucrose with glucansucrase, or lactic acid bacteria expressing glucansucrase, or a processed product thereof.

[0042] [Application] (Function / Action) The composition of this embodiment can be used to improve the intestinal flora.

[0043] Improvement of the intestinal flora includes promoting the growth of bacteria of the genus Parabacteroides, and also includes promoting the growth of bacteria of the genus Bifidobacterium, and also includes promoting the growth of both.

[0044] In the present invention, the term "Parabacteroides bacteria" refers to bacteria identified as belonging to the genus Parabacteroides by molecular phylogenetic analysis based on the 16S rRNA gene. The same applies to bacteria of the genus Bifidobacterium. Criteria for determining genera based on molecular phylogenetic analysis based on the 16S rRNA gene are well known to those skilled in the art (Stackebrandt E, Ebers J. Taxonomic parameters revisited: tarnished gold standards. Microbiol Today 2006;33:152-155).

[0045] With regard to improving the intestinal flora, promoting the growth of specific bacteria means increasing the proportion (occupancy) of specific bacteria in the intestinal flora.

[0046] Whether a certain component promotes the growth of specific bacteria in the intestinal microbiota can be evaluated as follows: Feces provided by a healthy subject is added to an appropriate medium and, if necessary, cultured for a certain period of time. After that, the component to be evaluated is added and cultured under appropriate conditions (e.g., 37°C, anaerobic conditions, simulating intestinal conditions, for 48 hours), and the occupancy rate of the specific bacteria in the microbiota in the culture is measured. The measurement results are then compared with those of a culture cultured under identical conditions except for the addition of a control (e.g., sterilized water) instead of the component to be evaluated. If the occupancy rate is higher than that of the control, it can be determined that growth has been promoted, and if it is lower, it can be determined that growth has been inhibited.

[0047] The occupancy rate of a specific bacterium in a bacterial flora can be determined by known methods. One preferred method is to perform 16S metagenomic analysis (sequencing analysis of 16S rRNA gene amplicons) on DNA extracted from the culture. When performing 16S metagenomic analysis, DNA can be extracted using a commercially available kit. The genomic region to be analyzed is not particularly limited as long as it allows identification of the bacterium, but the V3-V4 region of the 16S rRNA gene can be used. Primers, amplification conditions, amplicon purification, and other methods for bacterial analysis are also well known to those skilled in the art. It is preferable to use a next-generation sequencer with higher performance for sequencing. QIIME 2 is used to analyze the obtained data. TM For 16S metagenomic analysis, those skilled in the art can refer to information such as Sanschagrin S, Yergeau E. Next-generation sequencing of 16S ribosomal RNA gene amplicons. J Vis Exp. 2014;(90):51709. Published 2014 Aug 29. doi:10.3791 / 51709.

[0048] Parabacteroides bacteria are bacteria that inhabit the intestines. Promoting the growth of Parabacteroides bacteria is expected to be effective against inflammation, obesity, glucose metabolism disorders, hepatic steatosis, and cancer (Non-Patent Documents 1 to 3). It has also been reported that P. distasonis is reduced in patients with multiple sclerosis (MS) (Non-Patent Document 4), and that a combination of Parabacteroides bacteria with bacteria of the genera Oscillospira, Rickenellaceae, and Parabacteroides can distinguish between patients with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRLs) (Non-Patent Document 5). Therefore, the composition can be used for the treatment of any condition selected from the group consisting of inflammation, obesity, glucose metabolism disorders, multiple sclerosis (MS), hepatic steatosis, and cancer.

[0049] It has also been reported that oral administration of Parabacteroides goldsteinii improved weight loss and elevated inflammatory cytokines in lung tissue in a mouse model of smoking-induced chronic obstructive pulmonary disease (COPD), and the mechanism behind this improvement has been suggested to be that pentaacyl lipopolysaccharide, a cell wall component of Parabacteroides goldsteinii, antagonizes activation of the TLR4 receptor by inflammatory hexaacyl lipopolysaccharide derived from intestinal bacteria (Non-Patent Document 6). Therefore, the composition can be used for the treatment of chronic obstructive pulmonary disease (COPD).

[0050] Inflammation includes inflammatory bowel disease. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. Obesity refers to the excessive accumulation of fat in the body (BMI of 25 or higher). Obesity is defined as a condition in which obesity leads to health-threatening diseases or visceral obesity. Glucose metabolism disorders refer to conditions in which glucose metabolism is abnormal, including insulin resistance and diabetes. Insulin resistance refers to a condition in which target organs are less sensitive to insulin and its action is impaired, despite insulin secretion from the pancreas into the bloodstream. Insulin resistance reduces the glucose uptake capacity of muscle and adipose tissue, leading to uncontrolled gluconeogenesis in the liver, making it difficult to lower blood glucose levels and requiring more insulin to restore blood glucose levels to normal. If this condition persists, the pancreas' insulin secretory function declines, resulting in elevated blood glucose levels and leading to type 2 diabetes. Insulin resistance can be caused by genetic factors, obesity, lack of exercise, a high-fat diet, or stress. Diabetes is a disease in which hyperglycemia persists chronically due to insufficient insulin action, and includes both type 1 and type 2 diabetes. Multiple sclerosis (MS) is a demyelinating disease that occurs spatially and temporally in the central nervous system (brain, spinal cord, and optic nerves), and includes remitting-relapsing, primary progressive, and secondary progressive forms. Hepatic steatosis includes fatty liver (fatty liver disease), alcoholic fatty liver, and non-alcoholic fatty liver disease (NAFLD) (simple fatty liver).Cancer includes lung cancer, breast cancer, stomach cancer, colorectal 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 also called emphysema or chronic bronchitis.The main cause of COPD is smoking, and it is said that developing COPD affects not only the lungs but also organs throughout the body, making people more susceptible to diabetes, arteriosclerosis, osteoporosis, peptic ulcers, and other conditions.

[0051] The composition can also be used to treat diseases or conditions that are improved by promoting the growth of Parabacteroides bacteria in the intestine, such as inflammation, chronic obstructive pulmonary disease (COPD), obesity, glucose metabolism disorders, multiple sclerosis (MS), hepatic steatosis, and cancer, among others.

[0052] Bifidobacterium bacteria are inhabitants of the intestine and produce short-chain fatty acids (mainly lactic acid and acetic acid) from glucose. It is known that the action of Bifidobacterium bacteria or the short-chain fatty acids they produce regulates intestinal function. The production of short-chain fatty acids lowers the pH in the large intestine, thereby increasing the solubility of minerals, allowing them to pass through mucosal cells and promote their absorption (Mineral Absorption-Promoting Effect of Indigestible Carbohydrates (Fructooligosaccharides),” Journal of the Japanese Society of Nutrition and Food Science, Vol. 52, No. 6, pp. 387-395). Therefore, the composition can be used to regulate intestinal function and promote mineral absorption. 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, among these minerals.

[0053] The composition can also be used to treat diseases or conditions that can be improved by promoting the growth of Bifidobacterium bacteria in the intestines. Treatments for such diseases or conditions can include various treatments, such as intestinal regulation and promotion of mineral absorption.

[0054] The conditions referred to as diseases or conditions that can be improved by promoting the growth of Parabacteroides bacteria in the intestine or by promoting the growth of Bifidobacterium bacteria in the intestine include those in which the growth of Parabacteroides bacteria or Bifidobacterium bacteria in the intestine further increases in intestinal bacteria whose growth is desirable, and decreases in intestinal bacteria whose reduction is desirable.

[0055] In the present invention, the term "treatment" (non-therapeutic treatment) for a disease or condition includes reducing the risk of onset, delaying onset, prevention, assisting in treatment, halting progression, and maintaining or delaying the condition. Assisting in treatment is a non-therapeutic action, and includes assisting in radical treatment (treatment to eliminate the cause) and assisting in symptomatic treatment (treatment to improve symptoms). Details of assisting in treatment will be described later. Actions for improvement or treatment include non-therapeutic actions performed by physicians or persons other than physicians, such as pharmacists, nutritionists (including registered dietitians and sports nutritionists), public health nurses, midwives, nurses, clinical laboratory technicians, sports instructors, pharmaceutical manufacturers, pharmaceutical distributors, food manufacturers, and food distributors. Furthermore, prevention or reducing the risk of onset includes recommending the intake of specific foods and nutritional guidance (including nutritional guidance necessary for the recuperation of injured or sick persons, and nutritional guidance for maintaining and improving health).

[0056] (Intestinal flora and its improvement) In general, the intestinal flora may include, but is not limited to, the following bacteria: Bacteria of the genus Parabacteroides, bacteria of the genus Bifidobacterium, 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 ATCC 8482, 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 sp. 2_2_4, Eubacterium rectale M104 1, Bacteriodes xylanisolvens XB1A, Coprococcus comes SL7 1, Bacteroides sp. D1, Bacteroides sp.D4, 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, Clostridium sp L2-50, Clostridium nexile, Bacteroides pectinophilus, Anaerotruncus colihominis, Ruminococcus gnavus, Bacteroides intestinalis, Bacteroides fragilis 3_1_12, Clostridium asparagiforme, Enterococcus faecalis TX0104, Clostridium scindens, Blautia hansenii (Nature 464, 59-65 (2010) doi:10.1038 / nature08821).

[0057] In general, bacteria in the gut microbiota interact with each other and coexist symbiotically. Therefore, when specific bacteria increase in the gut microbiota (increase in occupancy), it is thought that the bacteria are interacting with each other and causing the proliferation of the target bacteria. Interactions can occur through quorum sensing, exchange of substances and nutrients between bacteria, or exchange of substances via membrane vesicles. Such interactions are sometimes referred to as communication, or chemical communication, since they involve chemical communication. Organic acids (pH control) and bile acids (surfactant-based antibacterial effects, sensitivity of which varies among bacteria) can affect the gut microbiota. However, specific bacteria may alter the pH to favor their own environment, thereby promoting their growth (Front Microbiol. 2021 Jan 28:12:611413. doi: 10.3389 / fmicb.2021.611413., Nature (2021), volume 599, pages 458–464).

[0058] In this embodiment, the improvement of the intestinal bacterial flora includes promoting the growth of bacteria of the genus Parabacteroides, and also includes promoting the growth of bacteria of the genus Bifidobacterium. However, the improvement of the intestinal bacterial flora is achieved by including various pathways upstream and downstream of the promotion of the growth of bacteria of the genus Parabacteroides or Bifidobacterium.

[0059] In one aspect, improvement of the intestinal bacterial flora can be achieved by, but is not limited to, any of the following (note that, in the following, leucrose and oligosaccharides having leucrose as their constituent sugar will be explained using leucrose as an example, but the explanation also applies to any oligosaccharides having leucrose as their constituent sugar other than leucrose. Furthermore, in the following, Parabacteroides bacteria will be explained as an example, but the explanation also applies to Bifidobacterium bacteria, among bacteria of the genus Parabacteroides): (a) Growth of Parabacteroides bacteria by leucrose (b) The proliferation of Parabacteroides bacteria by at least one metabolic product of leucrose produced by at least one intestinal bacterium other than Parabacteroides bacteria (hereinafter, "intestinal bacterium other than Parabacteroides bacteria" will be simply referred to as "other intestinal bacterium"). (c) The proliferation of Parabacteroides spp. due to the proliferation of at least one other intestinal bacterium by leucine, thereby reducing the number of other intestinal bacteria that compete with at least one Parabacteroides spp. (d) Proliferation of Parabacteroides bacteria through leucrose-mediated gut bacterial communication (e) The proliferation of Parabacteroides due to the reduction of other intestinal bacteria that compete with Parabacteroides by at least one metabolic product of leucrose produced by Parabacteroides.

[0060] (subject) The composition of this embodiment is suitable for administration to healthy subjects for whom it is desirable or necessary to promote the growth of Parabacteroides bacteria in the intestines; healthy subjects for whom it is desirable or necessary to promote the growth of Bifidobacterium bacteria in the intestines; healthy subjects who smoke; subjects prone to constipation, diarrhea, or mineral deficiency, and subjects for whom it is desirable or necessary to supplement minerals; healthy subjects with a disease or condition that can be improved by promoting the growth of Parabacteroides bacteria in the intestines; and healthy subjects with a condition that can be improved by promoting the growth of Bifidobacterium bacteria in the intestines. Subjects for whom it is desirable or necessary to promote the growth of Parabacteroides bacteria in the intestines include those with a low number of Parabacteroides bacteria in the intestines. Subjects for whom it is desirable or necessary to promote the growth of Bifidobacterium bacteria in the intestines include those with a low number of Bifidobacterium bacteria in the intestines. In the present invention, the term "administer" is used not only to mean administering a pharmaceutical to a subject, but also to mean having a subject ingest food or the like other than a pharmaceutical. A healthy subject refers to a human or a companion animal (described below) that has not been diagnosed with any disease (pre-disease). In other words, when the composition of the present embodiment is used on such healthy subjects, the composition of the present embodiment is not provided for therapeutic purposes.

[0061] 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 or the like (for example, as a food composition). In the above-mentioned aspect, the composition is not a medicine, but is provided in the form of, for example, a supplementary food, health food, or supplement. Non-therapeutic use refers to use to maintain the condition of a subject, temporarily improve (reduce symptoms), support, or take care of a certain condition.

[0062] The composition of this embodiment is suitable for administration to subjects with a disease for whom it is desirable or necessary to promote the growth of Parabacteroides bacteria in the intestine; subjects with a disease for whom it is desirable or necessary to promote the growth of Bifidobacterium bacteria in the intestine; subjects with a disease who are smokers; subjects prone to constipation, diarrhea, or mineral deficiency, and subjects for whom it is desirable or necessary to supplement minerals; subjects with a disease or condition that can be improved by promoting the growth of Parabacteroides bacteria in the intestine; and subjects with a disease for whom it is desirable or necessary to promote the growth of Bifidobacterium bacteria in the intestine. Subjects for whom it is desirable or necessary to promote the growth of Parabacteroides bacteria in the intestine include those with a low number of Parabacteroides bacteria in the intestine. Subjects for whom it is desirable or necessary to promote the growth of Bifidobacterium bacteria in the intestine include those with a low number of Bifidobacterium bacteria in the intestine. In the present invention, "administer" is used to mean having a subject ingest food or the like other than a pharmaceutical product. A subject having a disease refers to a human who has been diagnosed with any disease or a companion animal as described below. When the composition of the present embodiment is used for subjects having such a disease, the composition is not provided for therapeutic purposes, but for non-therapeutic purposes such as to assist in treatment.

[0063] The composition of this embodiment can be used for non-therapeutic purposes in subjects with a disease. In one embodiment, the composition of this embodiment can be used as a composition to support treatment in the form of a food or the like (e.g., as a food composition). Here, "supporting treatment" refers to non-therapeutic uses for treating a disease or illness. Examples of supporting treatment include use in subjects undergoing treatment for a disease or illness to enhance the therapeutic effect or provide nutritional support during treatment, use in subjects who have been treated for a disease or illness to improve the prognosis or provide nutritional support after treatment, and use in subjects scheduled to be treated for a disease or illness to enhance the therapeutic effect after treatment or provide nutritional support before treatment. In these embodiments, the composition is provided not as a pharmaceutical but in the form of, for example, a supplementary food, health food, or supplement.

[0064] When the composition of the present embodiment is used for non-therapeutic purposes, judgments as to whether it is desirable or necessary include judgments as non-therapeutic actions such as advice other than diagnosis by medical professionals such as doctors, nurses, pharmacists, midwives, and clinical laboratory technicians, judgments by those involved in non-therapeutic actions such as nutritionists (including registered dietitians and sports nutritionists), public health nurses, sports instructors, pharmaceutical manufacturers, pharmaceutical distributors, food manufacturers, and food distributors, judgments by the subject themselves or their family, etc. Furthermore, the above judgments include judgments based on the output results of questionnaires on lifestyle habits, eating habits, and subjective symptoms, and judgments based on subjective symptoms (concerns about obesity or lifestyle-related diseases, etc.).

[0065] The subject may be a human or a non-human animal. Non-human animals include mammals, birds, reptiles, amphibians, fish, etc. Non-human animals may be commercial animals, research animals, or companion animals. The phrase "companion animal" refers to a domestic or domestic animal whose physical, emotional, behavioral, and social needs can be readily met as a domestic companion or through close daily association with one or more humans. In one embodiment, species included within the definition of companion animal include dogs, canines, cats, felines, cows, horses, goats, sheep, pigs, primates (such as monkeys), rabbits, ferrets, rodents (such as guinea pigs, hamsters, mice, and rats), and other small mammals. In another embodiment, species included within the definition of companion animals are dogs, cats, horses, rabbits, ferrets, guinea pigs, and other small mammals, birds, small reptiles, fish, and livestock animals.

[0066] The age of the subject is not particularly limited, and when the subject is a human, it may be, for example, a newborn (within 28 days of birth); an infant (less than 1 year of age); a toddler (1 to 6 years of age); a child (7 years of age or older, but less than 15 years of age); an adult (15 years of age or older); a person 60 years of age or older; or a person 65 years of age or older. Furthermore, as people enter old age, the amount of Bifidobacterium in the intestines decreases, and in some subjects, it is not detected at all (Journal of Intestinal Microbiology 25: 113-124, 2011). Therefore, in one embodiment, the composition is preferably administered to people aged 65 or older. Furthermore, Parabacteroides may decrease with age (Park et al. BMC Microbiology (2021) 21:151). Therefore, in another embodiment, the composition is preferably administered to adults (15 years of age or older), and more preferably to people aged 65 or older.

[0067] [Composition] (Food composition, etc.) The composition of this embodiment may be a food composition or a pharmaceutical composition. Foods and pharmaceuticals, unless otherwise specified, include not only those for humans but also those for non-human animals. Unless otherwise specified, foods include general foods, functional foods, and nutritional compositions, as well as therapeutic foods (those intended for therapeutic purposes, prepared based on a menu prepared by a nutritionist or other professional prescribed by a doctor), dietary therapy foods, ingredient-adjusted foods, nursing care foods, and therapeutic support foods. Unless otherwise specified, foods include not only solids but also liquids, such as beverages, energy drinks, liquid diets, and soups. Functional foods refer to foods that can impart specific functionality to the body, and include a wide range of health foods, including foods with specified health uses (including conditional FOSHUs [specified health foods]), foods with functional claims, foods with nutrient function claims, foods for special dietary uses, foods with special dietary uses, dietary supplements, health supplements, supplements (e.g., tablets, coated tablets, sugar-coated tablets, capsules, liquids, etc.), and beauty foods (e.g., diet foods). Furthermore, in the context of the present invention, the term "functional food" encompasses health foods to which a health claim based on the Codex Alimentarius (the Joint FAO / WHO Food Standards Commission) is applied. The composition may also be a purified product of a specific sugar. Purified products include fractions, partially purified products, and crudely purified products.

[0068] (Route of administration, etc.) The composition of the present embodiment may be administered orally, parenterally, for example, via a tube (gastrostomy, enterostomy), or nasally, but is preferably administered orally.

[0069] The composition can be administered to a subject repeatedly or continuously for a long period of time. The period is not particularly limited, but to ensure sufficient efficacy, it is recommended to administer the composition continuously for a relatively long period of time, for example, 3 days or more, 1 week or more, 2 weeks or more, 1 month or more, 3 months or more, 6 months or more, or 1 year or more.

[0070] The compositions may be administered routinely, proactively, such as when at high risk, or when the need arises. The compositions may be administered with a meal, before a meal, after a meal, between meals, or at the onset of the disease or condition that the composition is intended to ameliorate.

[0071] (dose, content) The dosage of the composition of the present embodiment may be any amount that achieves the desired effect, and may be appropriately determined taking into consideration various factors such as the age, weight, and symptoms of the subject. Furthermore, in this embodiment, each component in the composition is used at an intake level that guarantees safety or below the acceptable daily intake (ADI), with priority given to the food safety laws of each country.

[0072] The daily dose of the composition can be 0.5 g or more, 1 g or more, preferably 2 g or more, preferably 3 g or more, more preferably 5 g or more, and even more preferably 10 g or more, in terms of the amount of active ingredient. Regardless of the lower limit, the upper limit of the amount of active ingredient per day can be 80 g or less, 70 g or less, 60 g or less, 50 g or less, 40 g or less, 30 g or less, 20 g or less, or 15 g or less. When multiple active ingredients are contained in a composition, the amount of active ingredient refers to the total amount of the active ingredients contained.

[0073] Administration may be once a day or multiple times a day, for example, 2 to 10 times. The amount of active ingredient administered per dose can 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. The upper limit of the amount of active ingredient per dose, regardless of the lower limit, can 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.

[0074] The content of the active ingredient in the composition can be adjusted appropriately depending on the form of the composition. For example, when the composition is in a form to be eaten or consumed as is, such as fermented milk or a beverage, the content of the active ingredient per 100 g of the composition can be 0.01% or more, preferably 0.1% or more, more preferably 0.3% or more, and even more preferably 0.5% or more. The upper limit of the active ingredient per 100 g of the composition, regardless of the lower limit, can be 8% or less, 5% or less, 4% or less, or even 3% or less. Alternatively, the content of the active ingredient per solid content of the composition can be 0.1% or more, preferably 1% or more, more preferably 3% or more, and even more preferably 5% or more. The upper limit of the active ingredient per solid content, regardless of the lower limit, can be 80% or less, 50% or less, 40% or less, or even 30% or less. In the present invention, "%" means "mass %" unless otherwise specified.

[0075] (Other ingredients, additives) In accordance with the present invention, the composition may contain other active or nutrient ingredients that are acceptable as foods or pharmaceuticals. Examples of such ingredients include lipids (e.g., milk fat, vegetable oil, medium-chain fatty acid-containing oil), proteins (e.g., milk protein, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin (α-La), β-lactoglobulin (β-Lg), heat-denatured whey protein, and enzyme-treated whey protein), amino acids (e.g., lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), leucrose, and leucrose-containing compounds. These include carbohydrates other than oligosaccharides (glucose, sucrose, fructose, maltose, trehalose, erythritol, maltitol, isomaltulose, xylitol, dextrin, kojibiose, galactosyl kojibiose), vitamins (e.g., vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, biotin, folic acid, pantothenic acid, and nicotinic acid), minerals (e.g., copper, zinc, iron, cobalt, manganese), antibiotics, and dietary fiber.

[0076] In the present invention, the composition may contain a prebiotic other than the active ingredient. Prebiotics can be defined as indigestible food ingredients that have a beneficial effect on the host and improve the host's health by selectively altering the growth and activity of specific bacteria in the large intestine. The composition may contain one or more prebiotics other than the active ingredient.

[0077] The prebiotics other than the active ingredient are not particularly limited as long as they do not interfere with the effects of the active ingredient contained in the composition. Examples of prebiotics other than the active ingredient include galactooligosaccharides, fructooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, raffinose, lactulose, lactosucrose, soybean oligosaccharides, coffee oligosaccharides, dietary fiber, and gluconic acid.

[0078] The composition can also be used as a synbiotic, and may contain probiotics in addition to the active ingredient. Synbiotics are a combination of probiotics and prebiotics. Probiotics can be defined as microorganisms that have beneficial effects on the host when introduced into the intestines of the host in a live state.

[0079] The probiotics are not particularly limited as long as they do not interfere with the effects of the active ingredients contained in the composition. Known examples of probiotics include certain lactic acid bacteria.

[0080] The composition may further contain additives acceptable for use as food or pharmaceuticals, such as inert carriers (solid or liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, colorants, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavors, acidulants, and natural products. More specifically, examples of the additives include water, other aqueous solvents, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymers, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petrolatum, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, sucralose, stevia, aspartame, acesulfame potassium, citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, and vegetable juice.

[0081] (Dosage form / shape) The food composition of this embodiment may be prepared in any form, such as a solid, liquid, mixture, suspension, powder, granules, paste, jelly, gel, or capsule. The food composition of this embodiment may also be prepared in any form, such as a dairy product, supplement, confectionery, beverage, health drink, seasoning, sweetener, processed food, prepared dish, or soup. More specifically, the composition of this embodiment may be liquid food (semi-liquid food, concentrated liquid food, etc.), jelly, gel, powder, infant formula, infant formula, liquid milk, powdered or liquid milk for pregnant or nursing women, fermented milk, bar, mousse, chocolate, biscuits, ice cream, fermented milk, lactic acid bacteria drink, dairy drink, dairy beverage, soft drink, fruit juice drink, tablet, cheese, bread, biscuit, cracker, pizza crust, whiskey, bourbon, spirits, liqueur, wine, fruit wine, Japanese sake, Chinese sake, shochu, or beer. These products can be in the form of alcoholic beverages such as non-alcoholic beer with an alcohol content of 1% or less, low-malt beer, other miscellaneous alcoholic beverages, and chuhai (Japanese shochu highballs); mineral water; processed egg products; processed seafood and meat products (including liver and other offal) (including delicacies); miso, soy sauce, furikake (rice seasoning), and other seasonings; soups such as miso soup; foods for the sick; nutritional foods; frozen foods; and processed foods. They can also be in the form of granules, powders, pastes, thickened liquids, etc., to be mixed with beverages or foods for administration. Granules and powders can be in cube or stick form (single-serving packets). Mineral water includes both sparkling and non-sparkling mineral water. In the present invention, modified milk powder refers to a powdered product prepared by processing raw milk, cow's milk, special cow's milk, or raw buffalo milk, or foods made from these ingredients, or using these as the main ingredient, and adding nutrients necessary for infants. In the present invention, modified liquid milk refers to raw milk, cow's milk, special cow's milk, raw buffalo milk, or foods made from these as raw materials, which are processed or used as the main raw material, and to which nutrients necessary for infants are added and made into a liquid, as defined in the Ministerial Ordinance on Milk, etc.

[0082] The pharmaceutical composition of the present embodiment can be in any dosage form suitable for oral administration, such as a solid preparation such as a tablet, granule, powder, pill, or capsule; a liquid preparation such as a solution, suspension, or syrup; a gel; or an aerosol.

[0083] (others) In the production of the composition of this embodiment, the stage of blending the active ingredient can be selected as appropriate. The stage of blending is not particularly limited as long as it does not significantly impair the properties of the active ingredient. For example, the active ingredient can be blended by mixing it with raw materials. Alternatively, the active ingredient can be added at the final stage of production to produce a composition containing the active ingredient.

[0084] The composition of this embodiment can be labeled with the intended use (application), and can also be labeled with a recommendation for administration to a specific subject.

[0085] The composition of the present embodiment has the following properties: the composition or active ingredient can (appropriately) increase the number of Parabacteroides bacteria in the intestines (in the intestinal tract, in the stomach), increase the rate of Parabacteroides bacteria in the intestinal flora, promote the growth of Parabacteroides bacteria in the intestines, treat diseases or conditions that are improved by promoting the growth of Parabacteroides bacteria in the intestines, (appropriately) increase the number of Bifidobacterium bacteria (bifidobacteria) in the intestines (in the intestinal tract, in the stomach), increase the rate of Bifidobacterium bacteria (bifidobacteria) in the intestinal flora, and promote the growth of Bifidobacterium bacteria in the intestines. It can be displayed that the product can promote the growth of Bifidobacterium bacteria (bifidobacteria), can promote the growth of Bifidobacterium bacteria (bifidobacteria) in the intestines, can treat diseases or conditions that are improved by promoting the growth of Bifidobacterium bacteria (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, hepatic steatosis, and cancer, can maintain a good intestinal environment, regulate intestinal flora, regulate stomach condition, improve bowel movements, or improve the intestinal environment, and can also be displayed to recommend administration to specific subjects. Note that the respective terms may be prefixed with a period such as "temporary" or "long-term," as appropriate. Display can be direct or indirect. Examples of direct display are descriptions on tangible objects such as the product itself, packaging, containers, labels, tags, etc., while examples of indirect display include advertising and promotional activities by place or means such as websites, in-store, pamphlets, exhibitions, media seminars, books, newspapers, magazines, television, video streaming sites, social media, influencer marketing, radio, mail, email, and audio.

[0086] In one embodiment, the recommendation to take the composition is displayed personally. Such a display can be made using a document (whether written or electronic) addressed to the subject, a device of the subject, such as a tablet, smartphone, or personal computer, or the subject's social networking site, etc. Furthermore, such a display can be made together with the results of any test or analysis of the subject, such as a gut flora test, a test for substances in feces, or a fecal metabolome analysis.

[0087] [Other embodiments] In this embodiment, a food information providing device is provided, comprising: an information acquisition unit that acquires information on the subject's intestinal microbiota; A derivation unit that derives information about food to be provided to the subject based on information about the intestinal flora; and A provision unit that provides the derived food information to the target. The information acquisition unit may include a feces collection unit and a feces pre-treatment unit (freezing treatment, anaerobic storage, nucleic acid extraction and purification unit), which may be installed inside the toilet bowl.

[0088] In a preferred embodiment, the information acquisition unit of the device acquires information on the presence or absence or amount of Parabacteroides bacteria from information on the intestinal flora, and the derivation unit derives information on a food composition containing any one selected from the group consisting of leucrose and oligosaccharides having leucrose as a constituent sugar based on the information on the presence or absence or amount of Parabacteroides bacteria. Alternatively, the information acquisition unit of the device acquires information on the presence or absence or amount of Bifidobacterium bacteria from information on the intestinal flora, and the derivation unit derives information on a food composition containing leucrose based on the information on the presence or absence or amount of Bifidobacterium bacteria.

[0089] In one aspect, the food information providing device can display the provided food information on a target terminal. In another aspect, the device further includes a display unit that displays the provided food information. The display unit can be a target terminal, such as a tablet terminal, a smartphone, or a personal computer.

[0090] In one aspect, the food information providing device may include an analysis unit that analyzes the bacterial flora of a sample obtained from the subject, and may also include an order receiving unit that receives an order for food from the subject based on the provided food information.

[0091] This embodiment also provides a food information providing method, which includes the following steps: Obtain information on the subject's gut microbiota; Deriving information about the foods to be provided to the subject based on the information about the intestinal microbiota; and The derived food information is provided to the subject.

[0092] In a preferred embodiment, the step of acquiring information involves acquiring information on the presence or absence or amount of Parabacteroides bacteria from information on the intestinal flora, and the step of deriving food information involves deriving information on a food that is a composition containing any one selected from the group consisting of leucrose and oligosaccharides having leucrose as a constituent sugar based on the information on the presence or absence or amount of Parabacteroides bacteria. Alternatively, the step of acquiring information involves acquiring information on the presence or absence or amount of Bifidobacterium bacteria from information on the intestinal flora, and the step of deriving food information involves deriving information on a food that is a composition containing any one selected from the group consisting of leucrose and oligosaccharides having leucrose as a constituent sugar based on the information on the presence or absence or amount of Bifidobacterium bacteria.

[0093] Such a method may further include displaying the food information to be provided on a target device, which may be, for example, a tablet device, a smartphone, a personal computer, or smart glasses.

[0094] The present invention will be described in more detail below using examples, although the technical scope of the present invention is not limited to these examples. [Example]

[0095] [Test Example 1] (fecal culture) Feces from healthy adults were suspended in a semi-solid medium for GAM glycolysis "Nissui" (Nissui Pharmaceutical Co., Ltd.) from which the agar had been removed by filtration, and each evaluation substance was added to a concentration of 1% to the diluted fecal solution.

[0096] The feces from three individuals were selected from three types of gut microbiota patterns (Ruminococcus, Bacteroides, and Prevotella) classified by the method of Arumugam M et al. (Nature 473: 174-180). Each type was tested without mixing. The culture medium used for the test was left to stand overnight in an anaerobic glove box before use. Cultures were performed in a BioLector Pro microbioreactor (m2p-Labs) and on a microchannel plate at 37°C and 600 rpm in an anaerobic environment for two days, maintaining a constant pH of 6.5 with 1.5 N hydrochloric acid and sodium hydroxide. The prebiotic potential of the test substance was evaluated by comparing the cultured bacterial flora with a control condition in which distilled water was added instead of the test substance.

[0097] The following substances were used for evaluation. Leucorse: Combi-Blocks "D-Leucorse" Code: QB-9615 Fructooligosaccharides (comparison example): Meiji Co., Ltd. (GF2 (kestose) 85% or more, other than GF3, etc.) Isomaltose (comparison example): Hayashibara Co., Ltd. "Isomaltose" Code: IM121

[0098] (Intestinal bacterial occupancy analysis using next-generation sequencing) After incubation, DNA was extracted and purified from the diluted fecal samples using the Maxwell RSC PureFood GMO & Authentication Kit (Promega), and amplicon sequencing of the V3-V4 region was performed using MiSeq (Illumina). The resulting .fastq files were analyzed using QIIME2 (https: / / qiime2.org / ) to calculate the occupancy rate of each enterobacteria.

[0099] The results for the Ruminococcus type, Bacteroides type, and Prevotella type are shown in Figures 1 to 3, respectively. An increase in the proportion of Parabacteroides bacteria was observed in the intestinal flora of all three subjects to whom leucrose was added. On the other hand, fructooligosaccharides and isomaltose, major prebiotic materials, did not show a significant increase in the proportion of Parabacteroides bacteria, and leucrose was overwhelmingly superior. Furthermore, in the system to which leucrose was added, changes in the proportion of various bacteria were observed throughout the flora, affecting the symbiotic relationship of the bacteria.

[0100] [Test Example 2] (fecal culture) Feces from healthy adults were suspended in a semi-solid medium for GAM saccharification "Nissui" (Nissui Pharmaceutical Co., Ltd.) from which the agar had been filtered, and leucrose (Combi-Blocks "D-Leucorse" code: QB-9615) was added to a 0.25% concentration (n=4). Each of the four feces samples was tested without mixing. The medium used for the test was left to stand overnight in an anaerobic glove box before use. A 96-well deepwell plate was used for the culture, and the culture was performed in an anaerobic environment at 37°C for one day. The prebiotic potential of the added test substance was evaluated by comparing the bacterial flora after culture with that of a control condition in which distilled water was added instead of leucrose.

[0101] (Intestinal bacterial occupancy analysis using next-generation sequencing) After incubation, DNA was extracted and purified from the diluted fecal samples using the Maxwell RSC PureFood GMO & Authentication Kit (Promega), and amplicon sequencing of the V3-V4 region was performed using MiSeq (Illumina). The resulting .fastq files were analyzed using QIIME2 (https: / / qiime2.org / ) to calculate the occupancy rate of each enterobacteria.

[0102] The results are shown in Figure 4. When leucrose was added, an increase in the occupancy of Parabacteroides and Bifidobacterium bacteria was observed. Furthermore, in the system where leucrose was added, changes in the occupancy of various bacteria were observed throughout the entire flora, affecting the symbiotic relationship of the bacteria.

[0103] [Summary of Test Examples 1 and 2] Parabacteroides bacteria are bacteria that inhabit the intestine. Promoting the growth of Parabacteroides bacteria is expected to be effective against inflammation, obesity, glucose metabolism disorders, hepatic steatosis, and cancer (Non-Patent Documents 1-3). It has also been reported that P. distasonis is reduced in patients with multiple sclerosis (MS) (Non-Patent Document 4), and that a combination of Parabacteroides bacteria with Oscillospira, Rickenellaceae, or Parabacteroides bacteria can distinguish between patients with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRLs) (Non-Patent Document 5). Therefore, based on Figures 1-4, it is believed that leucrose and oligosaccharides containing leucrose as a constituent sugar can be used to treat any of inflammation, obesity, glucose metabolism disorders, multiple sclerosis (MS), hepatic steatosis, and cancer.

[0104] Furthermore, it has been reported that oral administration of Parabacteroides goldsteinii improved weight loss and elevated inflammatory cytokines in lung tissue in a mouse model of smoking-induced chronic obstructive pulmonary disease (COPD), and the mechanism behind this improvement has been suggested to be that pentaacyl lipopolysaccharide, a cell wall component of Parabacteroides goldsteinii, antagonizes the activation of the TLR4 receptor by inflammatory hexaacyl lipopolysaccharides derived from intestinal bacteria (Non-Patent Document 6). Therefore, based on Figures 1 to 4, it is believed that leucrose and oligosaccharides containing leucrose as a constituent sugar can be used to treat chronic obstructive pulmonary disease (COPD).

[0105] It is known that bifidobacteria themselves or the short-chain fatty acids they produce act to regulate intestinal function, and that the production of short-chain fatty acids lowers the pH in the large intestine, thereby increasing the solubility of minerals, allowing them to pass through mucosal cells more easily and promoting their absorption into the cells (Non-Patent Document 7). Therefore, as shown in Figure 4, leucrose and oligosaccharides containing leucrose as a constituent sugar can be used to regulate intestinal function and promote mineral absorption. 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, among these minerals.

[0106] [Production Example 1: Production of a leucrose-containing composition using sucrose] (Preparation of enzyme solution) Lactobacillus satsumensis JCM12392, which had been activated and cultured in a commercially available MRS liquid medium, was subcultured at 1% into the medium shown below and cultured in a jar fermenter at 30°C for 27 hours while maintaining a constant pH of 6.4 with sodium hydroxide, and then cooled to below 10°C to terminate the culture. The resulting culture was centrifuged and the supernatant discarded, resulting in a Liquorilactobacillus satsumensis concentrate with a 15-fold bacterial cell concentration, which was used as the enzyme solution.

[0107] [Table 2]

[0108] (enzyme reaction) 65 w / w% sucrose and 0.5 w / w% enzyme solution 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). The results are shown in Figure 5. The composition contained leucrose, isomaltulose, trehalulose, and other sugars. The results of pretreatment using a GC solid-phase column and quantitative evaluation using three types of HPLC systems (NH column, Na ligand exchange column, and aqueous linked column) are shown in the table below (concentration w / w%) in the post-reaction composition (liquid, solids content 65 w / w%).

[0109] [Table 3]

[0110] Of the 6.6% of FG disaccharides, most was leucrose.

[0111] (summary) A composition containing leucrose was produced by treating a composition containing sucrose with Lactobacillus satsumensis JCM12392, which produces cell-bound glucansucrase. The produced composition contained leucrose as well as isomaltulose, trehalose, kojibiose, and isomaltose. [Industrial Applicability]

[0112] The present invention supports the maintenance and improvement of people's health by providing a composition for improving the intestinal microbiota, which contains either leucrose or an oligosaccharide having leucrose as its constituent sugar. The present invention also provides a food composition and a method for producing food that support the maintenance and improvement of people's health. Furthermore, the present invention can improve the nutrition of various people, ensure healthy lifestyles, and promote welfare.

[0113] [Sequence listed in the sequence listing] SEQ ID NOs:1-8 Amino acid sequence of glycoside hydrolase SEQ ID NOs:9-21 Amino acid sequence of glycoside hydrolase (partial)

Claims

1. A composition for improving the intestinal flora, comprising any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar.

2. The composition according to claim 1, wherein the improvement of the intestinal flora includes promoting the growth of bacteria of the genus Parabacteroides.

3. The composition according to claim 1, wherein the improvement of the intestinal flora includes promoting the growth of bacteria of the genus Bifidobacterium.

4. 10. The composition of claim 1 for use as a prebiotic or synbiotic.

5. A composition for treating any of inflammation, chronic obstructive pulmonary disease, obesity, glucose metabolism disorders, multiple sclerosis, hepatic steatosis, and cancer, comprising any of leucrose and oligosaccharides having leucrose as a constituent sugar.

6. The composition according to claim 5, wherein the treatment is by promoting the growth of Parabacteroides bacteria in the intestine.

7. A composition for treating a disease or condition that is ameliorated by promoting the growth of Parabacteroides bacteria in the intestine, comprising either leucrose or an oligosaccharide having leucrose as its constituent sugar.

8. A composition for promoting mineral absorption and regulating intestinal function, comprising either leucrose or an oligosaccharide having leucrose as its constituent sugar.

9. The composition according to claim 8, which promotes the growth of Bifidobacterium bacteria in the intestines.

10. A composition for treating a disease or condition that is ameliorated by promoting the growth of Bifidobacterium bacteria in the intestine, comprising either leucrose or an oligosaccharide having leucrose as its constituent sugar.

11. A composition described in any one of claims 1 to 10, comprising a composition selected from leucrose and oligosaccharides having leucrose as a constituent sugar, obtained by acting glucansucrase on a composition containing sucrose.

12. The composition according to claim 1 , wherein the composition comprises any one selected from isomaltulose, kojibiose, trehalulose, and isomaltose.

13. The composition according to claim 11, wherein the glucansucrase is a lactic acid bacterium or a processed product thereof.

14. A method for producing a composition containing leucrose, which comprises allowing a cell-bound glucansucrase to act on a composition containing sucrose.

15. The method according to claim 14, wherein the glucansucrase is derived from lactic acid bacteria.

16. The method according to claim 14, wherein glucansucrase is used as a lactic acid bacterium expressing glucansucrase.

17. The method according to claim 15 or 16, wherein the lactic acid bacterium is Liquorilactobacillus satsumensis.

18. an information acquisition unit that acquires information on the intestinal microbiota of the subject; A derivation unit that derives information about food to be provided to the subject based on information about the intestinal microbiota; and A provision section that provides the derived food information to the target Equipped with A food information providing device in which an information acquisition unit acquires information on the presence or amount of Parabacteroides bacteria or Bifidobacterium bacteria from information on the intestinal flora, and a derivation unit derives information on foods that are compositions containing either leucrose or oligosaccharides having leucrose as a constituent sugar based on the information on the presence or amount of Parabacteroides bacteria.

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

20. 20. The device according to claim 18 or 19, further comprising a display unit that displays information about the food to be served.

21. Obtaining information about the subject's gut microbiota; Deriving information about the food to be provided to the subject based on the information about the intestinal microbiota; and Provide the derived food information to the target The process includes the steps of: A food information providing method in which, in the information acquisition step, information on the presence or amount of Parabacteroides bacteria or Bifidobacterium bacteria is acquired from information on the intestinal flora, and, in the food information deriving step, information on a food that is a composition containing any one selected from leucrose and oligosaccharides having leucrose as a constituent sugar is derived based on the information on the presence or amount of Parabacteroides bacteria.

22. 22. The method of claim 21, further comprising displaying the food information to be provided on the target terminal.

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