Oral composition

Abstract

To provide an oral composition capable of promoting the demethylation of methoxy polyphenols.SOLUTION: The present invention provides: an oral composition wherein methoxy polyphenols and enteric bacteria are administered in combination; an oral composition comprising methoxy polyphenols and enteric bacteria; an oral composition comprising enteric bacteria to be administered in combination with methoxy polyphenols; and / or an oral composition comprising methoxy polyphenols to be administered in combination with enteric bacteria.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present disclosure relates to oral compositions. [Background technology]

[0002] Demethylated polyphenols, which are polyphenols that have had the methyl group removed from the methoxy group (methoxypolyphenols), include many compounds that exert useful effects in the body and compounds that can serve as raw materials for such compounds. For example, isoxanthohumol contained in hop extracts is converted to 8-prenylnaringenin by demethylation, which is known to have estrogen-like activity, disuse muscle atrophy inhibitory activity (Patent Document 1), and obesity inhibitory effect (Patent Document 2). It has been reported that conversion of isoxanthohumol to 8-prenylnaringenin is achieved by intestinal bacteria present in the intestines of mammals such as humans (Non-Patent Document 1). However, since there are individual differences in the presence of these intestinal bacteria and the conversion ability within the body, it has been reported that after ingesting isoxanthohumol, there are individual differences in the production amount and conversion rate of 8-prenylnaringenin produced from isoxanthohumol in the body (Non-Patent Document 2). Therefore, attempts have been made to isolate enterobacteria capable of converting isoxanthohumol to 8-prenylnaringenin, and specifically, it has been reported that Eubacterium limosum ATCC 8486 strain and Blautia producta ATCC 27340 strain demethylate the methoxy group of isoxanthohumol to produce 8-prenylnaringenin (Patent Document 3, Patent Document 4), but the reports are limited to a few types of bacteria. The intestinal flora is complex, and many of the bacteria that may be involved in demethylation in the intestine have not been identified. In order to improve the production volume of 8-prenylnaringenin from isoxanthohumol on an industrial scale, a method for promoting demethylation in a demethylation reaction using a polyphenol having a methoxy group as a starting material has been reported. Specifically, it has been reported that the production volume can be improved by culturing a microorganism that promotes the demethylation reaction together with a microorganism that performs the demethylation reaction in an in vitro culture solution under optimized conditions (Patent Document 5). Even in a document (Patent Document 6) that mentions improving intestinal metabolic levels by combining functional food ingredient materials with prebiotic or probiotic materials, no verification was conducted in the mammalian body, nor was there any mention of the production of 8-prenylnaringenin by demethylation of isoxanthohumol. The culture conditions have not been optimized, and the mechanism by which methoxypolyphenols are converted into useful compounds in the diverse bacterial flora of the intestinal microbiota of living organisms, or methods for promoting this conversion, are unknown. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2013-35811 A [Patent Document 2] International Publication No. 2021 / 125342 Brochure [Patent Document 3] Special Publication No. 2008-532558 [Patent Document 4] JP 2020-115858 A [Patent Document 5] International Publication No. 2022 / 202961 Brochure [Patent Document 6] Special Publication No. 2022-549839 [Non-patent literature]

[0004] [Non-Patent Document 1] J. Nutr. Vol. 136, Issue 7, pp. 1862-1867, July 2006 [Non-Patent Document 2] British J. Nut. Vol. 98, Issue 5, pp. 950-959, November 2007 Summary of the Invention [Problem to be solved by the invention]

[0005] An objective of the present disclosure is to provide an oral composition capable of promoting the demethylation of methoxypolyphenols. [Means for solving the problem]

[0006] The present disclosure includes the following aspects. [1] An oral composition in which methoxypolyphenols and enterobacteria are administered in combination. [2] An oral composition comprising methoxypolyphenols and enterobacteria. [3] An oral composition comprising enterobacteria administered in combination with methoxypolyphenols. [4] An oral composition comprising methoxypolyphenols administered in combination with enterobacteria. Effect of the Invention

[0007] According to the present disclosure, an oral composition can be provided in which a methoxypolyphenol and a microorganism capable of promoting demethylation of the methoxypolyphenol are administered in combination. [Brief description of the drawings]

[0008] [Figure 1] 1 is a graph showing the results of analyzing the amounts of 8-prenylnaringenin in urine samples from a control group, a low-dose lactic acid bacteria administration group, and a high-dose lactic acid bacteria administration group in Example 1. [Diagram 2]1 is a graph showing the results of analyzing the amounts of 8-prenylnaringenin in plasma samples from a control group, a low-dose lactic acid bacteria administration group, and a high-dose lactic acid bacteria administration group in Example 1. [Diagram 3] 1 is a graph showing the results of a comparative analysis of 8-prenylnaringenin levels in plasma samples after administration of isoxanthohumol, and after administration of isoxanthohumol and lactic acid bacteria in Example 2. [Figure 4] 1 is a graph showing the results of a comparative analysis of 8-prenylnaringenin levels in plasma samples after administration of isoxanthohumol, and after administration of isoxanthohumol and lactic acid bacteria in the low-productivity group (0.06 μM to 0.22 μM) in Example 2. [Diagram 5] 1 is a graph showing the results of a comparative analysis of 8-prenylnaringenin amounts in urine samples after administration of isoxanthohumol, and after administration of isoxanthohumol and lactic acid bacteria in the low-productivity group (0.06 μM to 0.22 μM) in Example 2. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] An embodiment of the present disclosure will be described in detail below. The present disclosure is not limited to the following embodiment, and can be implemented by making appropriate modifications within a range that does not impair the effects of the present disclosure. Each configuration and combination thereof in each embodiment is merely an example, and addition, omission, substitution, and other modifications of the configuration are possible as appropriate within the scope of the present disclosure. The present disclosure is not limited to the embodiments, but is limited only by the claims. Each feature disclosed herein may be combined with any other feature disclosed herein. In cases where a specific description given for one embodiment applies to other embodiments, the description may be omitted in the other embodiments. In this disclosure, the expression "X to Y" for a numerical range means "X or more and Y or less." In cases where a specific description given for one embodiment applies to other embodiments, the description may be omitted in the other embodiments. Unless otherwise specified, all numbers expressing features, items, amounts, parameters, characteristics, periods, etc. used in the specification and claims are understood to be modified in all cases by the term "about". As used herein, the term "about" means that the so specified feature, item, amount, parameter, characteristic, or period encompasses a range above and below the stated feature, item, amount, parameter, characteristic, or period value plus or minus 10 percent. At least, without limiting the application of the doctrine of equivalents to the scope of the claims, each numerical indicator should be interpreted in light of the number of reported significant digits and by applying ordinary rounding techniques. Any numerical range or value inherently includes a range of error necessarily resulting from the standard deviation found in their respective testing measurements. Unless otherwise specified, in this disclosure, each individual value of a numerical range is incorporated herein as if it were individually recited herein.

[0010] First embodiment (oral composition) The composition according to this embodiment is an oral composition in which the methoxy polyphenol and the microorganism are administered in combination. In one embodiment, the oral composition may be an oral composition comprising a methoxy polyphenol and a microorganism. In one embodiment, the composition may be an oral composition comprising a microorganism administered in combination with a methoxy polyphenol. In one embodiment, the composition may be an oral composition comprising a methoxy polyphenol administered in combination with a microorganism.

[0011] In one embodiment, the methoxy polyphenols and the microorganisms can be used for the preparation of an oral composition. In one embodiment, the microorganisms can be used for the preparation of oral compositions to be administered in combination with methoxy polyphenols. In one embodiment, methoxy polyphenols can be used to prepare oral compositions to be administered in combination with a microorganism.

[0012] In one embodiment, the methoxy polyphenols and the lactic acid bacteria are administered simultaneously, separately or sequentially.

[0013] Oral compositions may contain any active ingredient and / or one or more additives, non-limiting examples of which include buffers, pH adjusters, surfactants, excipients, preservatives, and antiseptics.

[0014] In the present disclosure, the term "individual" refers to a subject to which the oral composition or a food or medicine containing the same is administered, and is not limited to a range in which the oral composition can achieve the effect of promoting demethylation of methylated polyphenols, but is preferably a mammalian individual. Mammals include humans and non-human mammals. Non-human mammals include rats, mice, dogs, cats, monkeys, pigs, and cows.

[0015] (Methoxypolyphenols) Methoxypolyphenols are polyphenol compounds having a methoxy group on the side chain. The polyphenol compound having a methoxy group in the side chain may be one having one methoxy group or one having multiple methoxy groups.

[0016] In any case, the origin or raw material of the methoxy polyphenol is not limited as long as it contains methoxy polyphenol, but from the viewpoint of the richness of the content and ease of isolation, it is preferable that it is derived from a plant. The plant species may be either a seed plant or a non-seed plant, but is preferably a seed plant, and the seed plant may be either an angiosperm or a gymnosperm. The methoxy polyphenols may be derived from any organ of the plant, such as, for example, the roots, stems, leaves, flowers, fruits, and / or seeds. For example, when the methoxypolyphenol is a flavanone such as isoxanthohumol or xanthohumol, from the viewpoint of its rich content and ease of isolation, among angiosperms, it is preferable to use a plant of the Cannabaceae or Cucurbitaceae family, and as a Cannabaceae plant, a plant of the genus Humulus is preferable, and hops (humulone lupulone) is more preferable. As a Cucurbitaceae plant, a plant of the genus Citrullus is preferable, and watermelon (Citrullus lanatus) is more preferable. When the plant is hops or watermelon, the flavanones such as isoxanthohumol and xanthohumol are preferably derived from watermelon fruit or hop fruit, since the fruits of watermelon and hop are rich in methoxy polyphenols and flavanones such as isoxanthohumol and xanthohumol and are therefore suitable as materials.

[0017] In one embodiment, the oral composition is an oral composition in which plant-derived methoxy polyphenols and lactic acid bacteria are administered in combination. In one embodiment, the oral composition is an oral composition in which methoxy polyphenols derived from hops or watermelon and lactic acid bacteria are administered in combination. In one embodiment, the oral composition is one in which isoxanthohumol or xanthohumol derived from hops or watermelon is administered in combination with lactic acid bacteria.

[0018] Methoxy polyphenols can be isolated and obtained from plants by a method well known to those skilled in the art, such as solvent extraction and supercritical extraction. The methoxy polyphenols isolated from plants may be concentrated or diluted by a method well known to those skilled in the art to adjust their concentration. Methoxy polyphenols may be commercially available products sold by Fujifilm Wako Pure Chemical Industries, Kanto Chemical, etc.

[0019] Examples of polyphenol compounds having a methoxy group in the side chain include phenolic acids having a methoxy group in the side chain, lignans having a methoxy group in the side chain, chromans having a methoxy group in the side chain, coumarins having a methoxy group in the side chain, flavonoids having a methoxy group in the side chain, xanthones having a methoxy group in the side chain, and simple phenols having a methoxy group in the side chain.

[0020] Examples of phenolic acids having a methoxy group in the side chain include ferulic acid (having one methoxy group in the side chain), anisic acid (having one methoxy group in the side chain), vanillic acid (having one methoxy group in the side chain), and syringic acid (having two methoxy groups in the side chain).

[0021] Examples of lignans having a methoxy group in the side chain include pinoresinol (having two methoxy groups in the side chain) and secoisolariciresinol (having two methoxy groups in the side chain).

[0022] Examples of chromans having a methoxy group in the side chain include 6-methoxychroman (having one methoxy group in the side chain), 2-methoxychroman (having one methoxy group in the side chain), and 5-methoxychroman (having one methoxy group in the side chain).

[0023] Examples of coumarins having a methoxy group in the side chain include scoparone (having two methoxy groups in the side chain), scopoletin (having one methoxy group in the side chain), and isoscopoletin (having one methoxy group in the side chain).

[0024] Examples of flavonoids having a methoxy group in the side chain include anthocyanidins having a methoxy group in the side chain, flavans having a methoxy group in the side chain, flavanols having a methoxy group in the side chain (sometimes referred to as "catechins having a methoxy group in the side chain"), flavones having a methoxy group in the side chain, flavonols having a methoxy group in the side chain, flavanones having a methoxy group in the side chain, isoflavones having a methoxy group in the side chain, and chalcones having a methoxy group in the side chain. Examples of anthocyanidins having a methoxy group in the side chain include malvidin (having two methoxy groups in the side chain) and peonidin (having one methoxy group in the side chain). Examples of flavans having a methoxy group in the side chain include 4'-methoxyflavan (having one methoxy group in the side chain), 3'-methoxyflavan (having one methoxy group in the side chain), and 7-methoxyflavan (having one methoxy group in the side chain). Examples of flavanols having a methoxy group in the side chain include 3'-O-methylcatechin (having one methoxy group in the side chain), 4'-O-methylepicatechin (having one methoxy group in the side chain), and 4'-O-methylepigallocatechin (having one methoxy group in the side chain). Examples of flavones having a methoxy group in the side chain include nobiletin (having six methoxy groups in the side chain), sinensetin (having five methoxy groups in the side chain), tangeretin (having five methoxy groups in the side chain), and wogonin (having one methoxy group in the side chain). Examples of flavonols having a methoxy group in the side chain include patuletin (having one methoxy group in the side chain), tamarixetin (having one methoxy group in the side chain), syringetin (having two methoxy groups in the side chain), and isalpinine (having one methoxy group in the side chain). Examples of flavanones having a methoxy group in the side chain include isoxanthohumol (having one methoxy group in the side chain) and hesperetin (having one methoxy group in the side chain). Examples of isoflavones having a methoxy group in the side chain include glycitein (having one methoxy group in the side chain), biochanin (having one methoxy group in the side chain), formononetin (having one methoxy group in the side chain), and tectorigenin (having one methoxy group in the side chain). An example of a chalcone having a methoxy group in the side chain is xanthohumol (having one methoxy group in the side chain).

[0025] Examples of xanthones having a methoxy group in the side chain include α-mangostin (having one methoxy group in the side chain) and β-mangostin (having two methoxy groups in the side chain).

[0026] Examples of simple phenols having a methoxy group on the side chain include paeonol (having one methoxy group on the side chain) and anisole (having one methoxy group on the side chain).

[0027] In one embodiment, the methoxy polyphenol is preferably at least one selected from the group consisting of phenolic acids having a methoxy group in the side chain, lignans having a methoxy group in the side chain, chromans having a methoxy group in the side chain, coumarins having a methoxy group in the side chain, flavonoids having a methoxy group in the side chain, xanthones having a methoxy group in the side chain, and simple phenols having a methoxy group in the side chain. In one embodiment, the methoxy polyphenol is more preferably a flavonoid having a methoxy group in the side chain. The flavonoid having a methoxy group in the side chain is preferably at least one selected from the group consisting of a flavanone having a methoxy group in the side chain and a chalcone having a methoxy group in the side chain. In one embodiment, the flavonoid having a methoxy group in the side chain is more preferably at least one selected from the group consisting of isoxanthohumol and xanthohumol.

[0028] (microorganisms) The microorganism is not limited as long as it is a microorganism capable of promoting the demethylation of methoxypolyphenols in an individual, i.e., capable of promoting the removal of at least one methyl group from the methoxy group of methoxypolyphenols. Here, promoting the elimination of a methyl group from a methoxy group may mean promoting the elimination of a methyl group by the microorganism itself having the activity of eliminating a methyl group from a methoxy group, or promoting the elimination of a methyl group by a substance other than the microorganism having the activity of eliminating a methyl group and the microorganism having the action of promoting that elimination, or promoting the elimination of a methyl group by the microorganism having the activity of eliminating a methyl group and having the action of promoting the elimination of a methyl group. The microorganism is preferably a microorganism that promotes the elimination of methyl groups from the methoxy group of methoxy polyphenols by other substances having methyl group elimination activity.The microorganism is preferably a bacterium, more preferably an enterobacterium.The microorganism may be one type of microorganism or multiple types of microorganisms.

[0029] In one embodiment, the microorganism is an enterobacteria.

[0030] In the case where the elimination of the methyl group from the methoxy group of the methoxy polyphenol by another substance occurs in the intestine of an individual, the microorganism being an intestinal bacterium makes it easier for the microorganism to promote the elimination of the methyl group from the methoxy group by the other substance in the intestine when the methoxy polyphenol and the microorganism are administered in combination to an individual. In this case, the other substance is a substance that is present at least temporarily in the intestine, and may be a microorganism, and is preferably an intestinal bacterium. In one embodiment, when the microorganism has a methyl group-eliminating activity and an action of promoting the elimination of the methyl group, the microorganism and the other substance may be the same kind of microorganism. The microorganism may be one kind of microorganism or multiple kinds of microorganisms. In one embodiment, the microorganism in this embodiment and the other substance are the same kind or different kinds of intestinal bacteria.

[0031] In the present embodiment, examples of intestinal bacteria that can promote demethylation of methoxypolyphenols include microorganisms belonging to lactic acid bacteria, microorganisms belonging to the genus Akkermansia, microorganisms belonging to the genus Anaerofustis, microorganisms belonging to the genus Anaerotruncus, microorganisms belonging to the genus Arcobacter, microorganisms belonging to the genus Bacteroides, microorganisms belonging to the genus Clostridium, microorganisms belonging to the genus Coprobacillus, microorganisms belonging to the genus Dielma, microorganisms belonging to the genus Escherichia, microorganisms belonging to the genus Eubacterium, microorganisms belonging to the genus Faecalicoccus, microorganisms belonging to the genus Finegoldia, microorganisms belonging to the genus Hungatella, microorganisms belonging to the genus Intestinimonas, microorganisms belonging to the genus Parascalar. Microorganisms belonging to the genus Parascardovia, microorganisms belonging to the genus Prevotella, microorganisms belonging to the genus Solobacterium, microorganisms belonging to the genus Sutterella, microorganisms belonging to the genus Bifidobacterium, microorganisms belonging to the genus Anaerostipes, microorganisms belonging to the genus Chitinophaga, microorganisms belonging to the genus Citrobacter, Clostridium Microorganisms belonging to the genus Clostridioides, microorganisms belonging to the genus Cryptobacterium, microorganisms belonging to the genus Edwardsiella, microorganisms belonging to the genus Klebsiella, microorganisms belonging to the genus Lacrimispora, microorganisms belonging to the genus Megasphaera, microorganisms belonging to the genus Parabacteroides, microorganisms belonging to the genus Providencia,Examples of such microorganisms include those belonging to the genus Ruminococcus, those belonging to the genus Yersinia, and those belonging to the genus Entrocloster.

[0032] Examples of microorganisms belonging to lactic acid bacteria include microorganisms belonging to the genus Carnobacterium, Enterococcus, Fructobacillus, Lactobacillus, Lactococcus, Leuconostoc, Oenococcus, Pediococcus, Sporolactobacillus, Streptococcus, Tetragenococcus, and Weissella.

[0033] Examples of microorganisms belonging to the genus Carnobacterium include microorganisms belonging to Carnobacterium divergens (eg, NBRC 15683 strain, etc.).

[0034] Examples of microorganisms belonging to the genus Enterococcus include microorganisms belonging to Enterococcus avium (e.g., NBRC100477 strain, etc.), microorganisms belonging to Enterococcus caccae (e.g., DSM 19114 strain, etc.), microorganisms belonging to Enterococcus faecalis subsp. liquefaciens (e.g., NRIC 1746 strain, etc.), and microorganisms belonging to Enterococcus hirae (e.g., JCM 8717 strain, JCM 8719 strain, NRIC 102 strain, NRIC 108 strain, etc.).

[0035] Examples of microorganisms belonging to the genus Fructobacillus include microorganisms belonging to Fructobacillus fructosus (eg, NBRC 3516 strain, etc.).

[0036] In the present disclosure, the microorganisms belonging to the genus Lactobacillus as microorganisms in the oral composition in which methoxy polyphenols and microorganisms are administered in combination include microorganisms corresponding to the genus Lactobacillus before reclassification, which were reclassified by Zheng et al. (Int. J. Syst. Evol. Microbiol. Vol. 70, pp. 2782-2858, 2020). The correspondence between the old name of the genus Lactobacillus before the reclassification and the new name after classification is shown in Table 1. [Table 1] TIFF2025073471000002.tif222170TIFF2025073471000003.tif118170

[0037] Microorganisms belonging to the genus Lactobacillus are, for example, microorganisms belonging to Lactobacillus acetotolerans (e.g., JCM 3825 strain, etc.), Lactobacillus acidifarinae (e.g., NBRC 107156 strain, etc.), Lactobacillus acidophilus (e.g., IFO 13951 strain, etc.), Lactobacillus agilis (e.g., JCM 1187 strain, etc.), Lactobacillus algidus (e.g., JCM 10491 strain, etc.), Lactobacillus alimentarius (e.g., NBRC 107156 strain, etc.), etc., according to the scientific names before the reclassification by Zheng et al. 106464 strain, etc.), microorganisms belonging to Lactobacillus amylolyticus (e.g., JCM 12529 strain, etc.), microorganisms belonging to Lactobacillus amylophilus (e.g., IFO 15881 strain, etc.), microorganisms belonging to Lactobacillus amylotrophicus (e.g., JCM 1124 strain, etc.), microorganisms belonging to Lactobacillus antri (e.g., JCM 15950 strain, etc.), microorganisms belonging to Lactobacillus apodemi (e.g., JCM 16172 strain, etc.), microorganisms belonging to Lactobacillus aquaticus (e.g., JCM 16869 strain, etc.), Lactobacillus aviarius subsp.Microorganisms belonging to Lactobacillus aviarius (e.g., NBRC 102162 strain, etc.), microorganisms belonging to Lactobacillus bifermentans (e.g., JCM 1094 strain, etc.), microorganisms belonging to Lactobacillus brantae (e.g., DSM 23927 strain, etc.), microorganisms belonging to Lactobacillus brevis (e.g., NRIC 1037 strain, etc.), microorganisms belonging to Lactobacillus buchneri (e.g., NRIC 1040 strain, NRIC 1079 strain, NRIC 1082 strain, etc.), microorganisms belonging to Lactobacillus camelliae (e.g., JCM 13995 strain, etc.), Lactobacillus Microorganisms belonging to Lactobacillus capillatus (e.g., JCM 15044 strain, etc.), microorganisms belonging to Lactobacillus casei (e.g., AHU 1055 strain, etc.), microorganisms belonging to Lactobacillus ceti (e.g., JCM 15609 strain, etc.), microorganisms belonging to Lactobacillus coleohominis (e.g., JCM 11550 strain, etc.), microorganisms belonging to Lactobacillus collinoides (e.g., NRIC 1049 strain, etc.), microorganisms belonging to Lactobacillus composti (e.g., JCM 14202 strain, etc.), microorganisms belonging to Lactobacillus curvatus (e.g., NBRC 15884 strain, etc.), microorganisms belonging to Lactobacillus delbrueckii (e.g., AHU 1056 strain, NBRC 102622 strain, etc.), Lactobacillus delbrueckii subsp.Microorganisms belonging to Lactobacillus delbrueckii subsp. indicus (e.g., JCM 15610 strain, etc.), microorganisms belonging to Lactobacillus delbrueckii subsp. lactis (e.g., IFO 3073 strain, JCM 1557 strain, NRIC 1061 strain, etc.), microorganisms belonging to Lactobacillus diolivorans (e.g., NBRC 107869 strain, etc.), microorganisms belonging to Lactobacillus equi (e.g., JCM 10991 strain, etc.), microorganisms belonging to Lactobacillus equicursoris (e.g., JCM 14600 strain, etc.), microorganisms belonging to Lactobacillus equigenerosi (e.g., JCM 14505 strain, etc.), microorganisms belonging to Lactobacillus fabifermentans (e.g., DSM 21115 strain, etc.), microorganisms belonging to Lactobacillus farraginis (e.g., JCM 14108 strain, etc.), and microorganisms belonging to Lactobacillus floricola (e.g., JCM 16512 strain, etc.). In addition, there are microorganisms belonging to Lactobacillus florum (e.g., JCM 16035 strain, etc.), Lactobacillus fructivorans (e.g., NBRC 13954, NRIC 224 strains, etc.), Lactobacillus frumenti (e.g., JCM 11122 strain, etc.), Lactobacillus fuchuensis (e.g., JCM 11249 strain, etc.), Lactobacillus gasseri (e.g., JCM 1131 strain, etc.), and Lactobacillus gastricus (e.g., JCM 11231 strain, etc.), all of which are classified under the scientific names before the reclassification by Zheng et al. 15952 strain, etc.), microorganisms belonging to Lactobacillus ghanensis (e.g., JCM 15611 strain, etc.), microorganisms belonging to Lactobacillus graminis (e.g., JCM 9503 strain, etc.), microorganisms belonging to Lactobacillus hammesii (e.g., JCM 16170 strain, etc.), microorganisms belonging to Lactobacillus hamsteri (e.g., JCM 6256 strain, etc.), microorganisms belonging to Lactobacillus harbinensis (e.g., NBRC 100982 strain, etc.), microorganisms belonging to Lactobacillus hayakitensis (e.g., JCM 14209 strain, etc.), microorganisms belonging to Lactobacillus hilgardii (e.g., DSM 20051 strain, NBRC 15886 strain, NRIC 1060 strain, etc.), microorganisms belonging to Lactobacillus hokkaidonensis (e.g., JCM 18461 strain, etc.), LactobacillusMicroorganisms belonging to Lactobacillus hominis (e.g., DSM 23910 strain, etc.), microorganisms belonging to Lactobacillus hordei (e.g., JCM 16179 strain, etc.), microorganisms belonging to Lactobacillus iners (e.g., JCM 12513 strain, etc.), microorganisms belonging to Lactobacillus ingluviei (e.g., JCM 12531 strain, etc.), microorganisms belonging to Lactobacillus intestinalis (e.g., JCM 7548 strain, etc.), microorganisms belonging to Lactobacillus iwatensis (e.g., JCM 18838 strain, etc.), microorganisms belonging to Lactobacillus jensenii (e.g., JCM 15953 strain, etc.), microorganisms belonging to Lactobacillus johnsonii (e.g., JCM 2012 strain, etc.), microorganisms belonging to Lactobacillus kalixensis (e.g., JCM 15954 strain, etc.), microorganisms belonging to Lactobacillus kefiranofaciens subsp. kefirgranum (e.g., JCM 8572 strain, etc.), microorganisms belonging to Lactobacillus kefiranofaciens subsp. kefirgranum (e.g., JCM 8572 strain, etc.), microorganisms belonging to Lactobacillus kefiri (e.g., NRIC 1693 strain, etc.), microorganisms belonging to Lactobacillus kimchiensis (e.g., JCM 17702 strain, etc.), Lactobacillus Microorganisms belonging to Lactobacillus kisonensis (e.g., JCM 15041 strain, etc.), microorganisms belonging to Lactobacillus kitasatonis (e.g., JCM 1039 strain, etc.), microorganisms belonging to Lactobacillus koreensis (e.g., JCM 16448 strain, etc.), Lactobacilluslactis (e.g., AHU 1059 strain, etc.), Lactobacillus leichmannii (e.g., AHU 1681 strain, etc.), Lactobacillus malefermentans (e.g., DSM 5705 strain, NRIC 1081 strain, etc.), Lactobacillus mali (e.g., NRIC 1076 strain, etc.), Lactobacillus manihotivorans (e.g., JCM 12514 strain, etc.), Lactobacillus mindensis (e.g., NBRC 107162 strain, etc.), Lactobacillus mixtipabuli (e.g., JCM 19805 strain, etc.), microorganisms belonging to the genus Lactobacillus murinus (for example, IFO 14221 strain, etc.), and microorganisms belonging to the genus Lactobacillus nagelii (for example, JCM 12492 strain, etc.). In addition, there are microorganisms belonging to Lactobacillus namurensis (e.g., NBRC 107158 strain, etc.), Lactobacillus nantensis (e.g., NBRC 107153 strain, etc.), Lactobacillus nasuensis (e.g., JCM 17158 strain, etc.), Lactobacillus nenjiangensis (e.g., JCM 30919 strain, etc.), Lactobacillus oeni (e.g., JCM 18036 strain, etc.), Lactobacillus oligofermentans (e.g., JCM 18036 ... 16175 strain, etc.), microorganisms belonging to Lactobacillus oris (e.g., JCM 11028 strain, etc.), microorganisms belonging to Lactobacillus oryzae (e.g., JCM 18671 strain, etc.), microorganisms belonging to Lactobacillus otakiensis (e.g., JCM 15040 strain, etc.), microorganisms belonging to Lactobacillus ozensis (e.g., JCM 17196 strain, etc.), microorganisms belonging to Lactobacillus panis (e.g., JCM 11053 strain, etc.), microorganisms belonging to Lactobacillus pantheris (e.g., NBRC 106106 strain, etc.), Lactobacillus parabrevis (e.g., Lactobacillus Microorganisms belonging to Lactobacillus parabrevis (e.g., NBRC 107154 strain, etc.), microorganisms belonging to Lactobacillus parabuchneri (e.g., NBRC 107865 strain, etc.), microorganisms belonging to Lactobacillus paracollinoides (e.g., JCM11969 strain, etc.), microorganisms belonging to Lactobacillus parafarraginis (e.g., JCM 14109 strain, etc.), microorganisms belonging to Lactobacillus parakefiri (e.g., NBRC 15890 strain, etc.), microorganisms belonging to Lactobacillus paralimentarius (e.g., NBRC 106466 strain, NBRC 107149 strain, NBRC 107152 strain, etc.), microorganisms belonging to Lactobacillus paraplantarum (e.g., NBRC 107151 strain, etc.), microorganisms belonging to Lactobacillus paucivorans (e.g., JCM 18045 strain, etc.), microorganisms belonging to Lactobacillus pentosiphilus (e.g., JCM 31145 strain, etc.), microorganisms belonging to Lactobacillus pentosus (e.g., IFO 12011 strain, NBRC 106467 strain, etc.), microorganisms belonging to Lactobacillus perolens (e.g., JCM 12534 strain, etc.), microorganisms belonging to Lactobacillus plantarum (e.g., DSM 13273 strain, IFO 3070 strain, NCIMB 8826 strain, NRIC 1068 strain, etc.), microorganisms belonging to Lactobacillus plantarum subsp. argentoratensis (e.g., NBRC 106468 strain, etc.), microorganisms belonging to Lactobacillus plantarum subsp. plantarum (e.g., NBRC 15891 strain, etc.), microorganisms belonging to Lactobacillus pobuzihii (e.g., NBRC 103219 strain, JCM18084 strain, etc.), microorganisms belonging to Lactobacillus pontis (e.g., JCM 11051 strain, etc.), microorganisms belonging to Lactobacillus porci (e.g., DSM 105804 strain, etc.), microorganisms belonging to Lactobacillus porcinae (e.g., JCM 19617 strain, etc.), microorganisms belonging to Lactobacillus rapi (e.g., NBRC 109618 strain, etc.), microorganisms belonging to Lactobacillus rhamnosus (e.g., DSM 20021 strain, IFO 3425 strain, etc.), microorganisms belonging to Lactobacillus rossiae (e.g., JCM 16176 strain, etc.), microorganisms belonging to Lactobacillus ruminis (e.g., NBRC 102161 strain, etc.), microorganisms belonging to Lactobacillus saerimneri (e.g., NBRC 107826 strain, etc.), and microorganisms belonging to Lactobacillus sakei subsp. carnosus (e.g., NBRC 107868 strain, etc.). In addition, there are microorganisms belonging to Lactobacillus salivarius subsp. salicinius (e.g., NRIC 1072 strain, etc.), Lactobacillus sanfranciscensis (e.g., JCM 5668 strain, etc.), Lactobacillus saniviri (e.g., JCM 17471 strain, etc.), Lactobacillus satsumensis (e.g., JCM 12392 strain, etc.), Lactobacillus secaliphilus (e.g., JCM 15613 strain, etc.), Lactobacillus senmaizukei (e.g., Lactobacillus satsumensis) (e.g., JCM 12392 strain, etc.), Lactobacillus secaliphilus (e.g., JCM 15613 strain, etc.), Lactobacillus Microorganisms belonging to Lactobacillus senmaizukei (e.g., NBRC 103853 strain, etc.), microorganisms belonging to Lactobacillus sharpeae (e.g., JCM 1186 strain, etc.), microorganisms belonging to Lactobacillus siliginis (e.g., NBRC 101315 strain, etc.), microorganisms belonging to Lactobacillus songhuajiangensis (e.g., JCM 30918 strain, etc.), Lactobacillus sp.) NRIC 1029 strain, microorganisms belonging to Lactobacillus spicheri (e.g., NBRC 107155 strain, etc.), microorganisms belonging to Lactobacillus sucicola (e.g., JCM 15457 strain, etc.), microorganisms belonging to Lactobacillus suebicus (e.g., JCM 9504 strain, etc.), microorganisms belonging to Lactobacillus sunkii (e.g., JCM 15039 strain, etc.), microorganisms belonging to Lactobacillus thailandensis (e.g., JCM 13996 strain, etc.), microorganisms belonging to Lactobacillus tucceti (e.g., JCM 18037 strain, etc.), microorganisms belonging to Lactobacillus ultunensis (e.g., JCM 16177 strain, etc.), microorganisms belonging to Lactobacillus uvarum (e.g., JCM 16870 strain, etc.), microorganisms belonging to Lactobacillus vaccinostercus (e.g., NRIC 1075 strain, etc.), microorganisms belonging to Lactobacillus versmoldensis (e.g., NBRC 106069 strain, etc.), microorganisms belonging to Lactobacillus vini (e.g., JCM 14280 strain, etc.), microorganisms belonging to Lactobacillus wasatchensis (e.g., DSM 29958 strain, etc.), microorganisms belonging to Lactobacillus xiangfangensis (e.g., NBRC 108914 strain, etc.), microorganisms belonging to Lactobacillus zeae (e.g., DSM 20178 strain, etc.), and microorganisms belonging to Lactobacillus zymae (e.g., NBRC 107157 strain, etc.). In addition, there are microorganisms belonging to Lactobacillus chiayiensis (e.g., NBRC 112906 strain, etc.), Lactobacillus apinorum (e.g., DSM 26257 strain, etc.), Lactobacillus ixorae (e.g., NBRC 111239 strain, etc.), Lactobacillus kullabergensis (e.g., DSM 26262 strain, etc.), Lactobacillus mellifer (e.g., DSM 26254 strain, etc.), and Lactobacillus modestisalitolerans (e.g., NBRC 111239 strain, etc.), which are based on the scientific names before the reclassification by Zheng et al. 107235 strain, etc.), microorganisms belonging to Lactobacillus plajomi (for example, NBRC 107333 strain, etc.), and microorganisms belonging to Lactobacillus suantsaiihabitans (for example, NBRC 113532 strain, etc.).

[0038] Examples of microorganisms belonging to the genus Lactococcus include microorganisms belonging to Lactococcus fujiensis (e.g., JCM 16395 strain, etc.), Lactococcus garvieae (e.g., NBRC 100934 strain, etc.), Lactococcus lactis subsp. lactis (e.g., NRIC 1074 strain, NRIC 1149 strain, etc.), Lactococcus lactis subsp. tructae (e.g., DSM 21502 strain, etc.), and Lactococcus taiwanensis (e.g., NBRC 109049 strain, etc.).

[0039] Examples of microorganisms belonging to the genus Leuconostoc include microorganisms belonging to Leuconostoc citreum (e.g., JCM 9698 strain, etc.), microorganisms belonging to Leuconostoc dextranicum (e.g., AHU 1078 strain, IFO 3347 strain, etc.), microorganisms belonging to Leuconostoc lactis (e.g., IFO 12455 strain, etc.), and microorganisms belonging to Leuconostoc mesenteroides subsp. cremoris (e.g., IAM 1087 strain, NRIC 1538 strain, etc.). Examples of microorganisms belonging to the genus Oenococcus include microorganisms belonging to Oenococcus oeni (eg, ATCC 27311 strain, DSM 20252 strain, etc.).

[0040] Examples of microorganisms belonging to the genus Pediococcus include microorganisms belonging to Pediococcus acidilactici (e.g., NRIC 1102 strain, etc.), microorganisms belonging to Pediococcus argentinicus (e.g., JCM 30771 strain, etc.), microorganisms belonging to Pediococcus cellicola (e.g., JCM 14152 strain, etc.), microorganisms belonging to Pediococcus claussenii (e.g., JCM 18046 strain, etc.), microorganisms belonging to Pediococcus damnosus (e.g., JCM 5886 strain, etc.), and microorganisms belonging to Pediococcus inopinatus (e.g., JCM 5886 strain, etc.). inopinatus (e.g., JCM 12518 strain, etc.), Pediococcus parvulus (e.g., JCM 5889 strain, etc.), and Pediococcus pentosaceus (e.g., IFO 3891 strain, NRIC 1106 strain, etc.).

[0041] Examples of microorganisms belonging to the genus Sporolactobacillus include microorganisms belonging to Sporolactobacillus inulinus (eg, NRIC 1133 strain, etc.).

[0042] Examples of microorganisms belonging to the genus Streptococcus include microorganisms belonging to Streptococcus alactolyticus (e.g., DSM 100950 strain, etc.), microorganisms belonging to Streptococcus equinus (e.g., NRIC 1139 strain, etc.), and microorganisms belonging to Streptococcus uberis (e.g., NRIC 1153 strain, etc.).

[0043] Examples of microorganisms belonging to the genus Tetragenococcus include microorganisms belonging to Tetragenococcus halophilus subsp. halophilus (eg, NBRC 100498 strain, etc.).

[0044] Examples of microorganisms belonging to the genus Weissella include microorganisms belonging to Weissella confusa (e.g., DSM 20196 strain, NBRC 106469 strain, etc.) and microorganisms belonging to Weissella halotolerans (e.g., NRIC 1627 strain, etc.).

[0045] In this embodiment, one or more kinds of the microorganisms may be used, and one or more strains may be used.

[0046] In one embodiment, the intestinal bacteria capable of promoting the demethylation of methoxypolyphenols are preferably microorganisms belonging to the genus Lactobacillus or Bifidobacterium (microorganisms belonging to the genus Bifidobacterium).

[0047] In one embodiment, the intestinal bacteria capable of promoting the demethylation of methoxypolyphenols are more preferably microorganisms belonging to the lactic acid bacteria group. As described above, the lactic acid bacteria are preferably microorganisms belonging to at least one genus selected from the group consisting of microorganisms belonging to the genus Carnobacterium, microorganisms belonging to the genus Enterococcus, microorganisms belonging to the genus Fructobacillus, microorganisms belonging to the genus Lactobacillus, microorganisms belonging to the genus Lactococcus, microorganisms belonging to the genus Leuconostoc, microorganisms belonging to the genus Oenococcus, microorganisms belonging to the genus Pediococcus, microorganisms belonging to the genus Sporolactobacillus, microorganisms belonging to the genus Streptococcus, microorganisms belonging to the genus Tetragenococcus, and microorganisms belonging to the genus Weissella.

[0048] In this embodiment, the microorganism is preferably a microorganism belonging to the genus Lactobacillus. Here, as described above, the microorganism belonging to the genus Lactobacillus includes microorganisms corresponding to the genus Lactobacillus before reclassification, which were reclassified by Zheng et al. (Int. J. Syst. Evol. Microbiol. Vol. 70, pp. 2782-2858, 2020). It is more preferable that the microorganism belonging to the genus Lactobacillus is Lactobacillus brevis. In this embodiment, the preferred microorganism is a microorganism belonging to the genus Levilactobacillus, more preferably Levilactobacillus brevis, according to the scientific name after reclassification by Zheng et al.

[0049] The effective dose of the oral composition can be appropriately determined by a person skilled in the art based on the animal species, age, weight, disease, etc. of the subject individual, the administration route, administration schedule, formulation form, etc., and is not limited as long as the desired effect of promoting demethylation of methoxy polyphenols is obtained in the individual. In one embodiment, 1×10 7 Microorganisms may be administered in amounts of 1×10 cfu or more per mg of methoxypolyphenol. 8 Microorganisms may be administered in amounts of cfu or more. In one embodiment, an individual may be administered 0.1 mg / day or more, 0.1-1000 mg / day, 0.1-500 mg / day, or 0.1-100 mg / day of methoxy polyphenols. In one embodiment, the individual is inoculated with at least 1×10 6 cfu / day or more, 1×10 7 cfu / day or more, 1×10 8 cfu / day or more, 1×10 8 ~1×10 13 cfu / day, or 1 × 10 8 ~1×10 12 cfu / day may be administered. In one embodiment, the individual is administered 0.1 to 100 mg / day of methoxy polyphenol and 1×10 8 ~1×10 12 cfu / day may be administered. In one embodiment, the individual is administered 0.1 to 100 mg / day of isoxanthohumol or xanthohumol and 1×10 8 ~1×10 12 cfu / day may be administered. In one embodiment, a human individual is administered 0.1 to 100 mg / day of isoxanthohumol or xanthohumol and 1×10 8 ~1×10 12 cfu / day may be administered.

[0050] The frequency of administration of the oral composition may be once a day, or the daily dose may be divided into several doses. Alternatively, the composition may be administered at any time when it is desired to promote demethylation of methoxy polyphenols, or may be administered once every few days or weeks, etc.

[0051] As described below in the "Uses" section, when a substance other than the microorganism causes the elimination of a methyl group from the methoxy group of a methoxy polyphenol in an individual, the elimination of the methyl group by the substance other than the microorganism can be promoted by administering a combination of a methoxy polyphenol and a microorganism to the individual. Therefore, the individual to which the oral composition is administered is preferably an individual in which methyl groups are removed from the methoxy group of methoxy polyphenols in the body. An example of an individual in which methyl groups are removed from the methoxy group of methoxy polyphenols is an individual having intestinal bacteria in the intestine of a mammal that has the activity of removing methyl groups from the methoxy group of methoxy polyphenols. By administering the oral composition of this embodiment to such an individual, it becomes easier to obtain the desired effect of promoting demethylation of methoxy polyphenols, it becomes easier to promote the production of demethylated polyphenols in the individual, and / or it becomes easier to increase the urinary concentration and / or blood concentration of demethylated polyphenols in the individual.

[0052] Such individuals can be identified by known methods. For example, the presence of demethylated polyphenols can be examined in samples such as feces, urine, and blood (whole blood, plasma, serum, etc.) collected from individuals after ingesting methoxy polyphenols. Demethylated polyphenols can be detected by spectrophotometric methods such as the Folin-Ciocalteu method and the Folin-Denis method.

[0053] (Demethylated polyphenols) As described below in the "Uses" section, the oral compositions of the present embodiments can be used to promote the production of demethylated polyphenols in an individual and / or to increase the urinary and / or blood levels of demethylated polyphenols in an individual.

[0054] In this embodiment, the demethylated polyphenol is a demethylated polyphenol compound in which a methyl group has been removed from the methoxy group of the above-mentioned "methylated polyphenol."

[0055] When a demethylated polyphenol compound is produced from a compound having one methoxy group in the side chain, the compound is produced by eliminating a methyl group from that one methoxy group. When a demethylated polyphenol compound is produced from a compound having multiple methoxy groups in the side chain, the compound may be produced by eliminating a methyl group from one of the multiple methoxy groups, or by eliminating methyl groups from multiple methoxy groups (not one methoxy group, not all methoxy groups) among the multiple methoxy groups, or by eliminating methyl groups from all methoxy groups among the multiple methoxy groups. In addition, when the methyl groups of multiple methoxy groups (not one methoxy group, not all methoxy groups) are eliminated from a compound having multiple methoxy groups, the methoxy groups remain in the resulting demethylated polyphenol compound, so the resulting demethylated compound can be used as a "methoxy polyphenol (polyphenol having a methoxy group in the side chain)". For example, when the methyl group of one methoxy group is eliminated from a compound having three methoxy groups, the resulting demethylated compound has two methoxy groups remaining, so the resulting demethylated compound can be used as a "methoxy polyphenol". In addition, the compound produced by removing the methyl group from the methoxy group of the above-mentioned "polyphenol compound having a methoxy group in the side chain" is sometimes referred to as a "demethylated polyphenol compound," and the same is also true for specific examples of "polyphenol compounds having a methoxy group in the side chain." For example, a product produced by removing the methyl group from a "phenolic acid having a methoxy group in the side chain" is sometimes called a "demethylated phenolic acid." Similarly, a product produced by removing the methyl group from a "lignan having a methoxy group in the side chain" is sometimes called a "demethylated lignan". Similarly, a product produced by removing the methyl group from a "chroman having a methoxy group in the side chain" is sometimes called a "demethylated chroman." Similarly, a product produced by removing the methyl group from a "coumarin having a methoxy group in the side chain" is sometimes called a "demethylated coumarin". Similarly, a product produced by removing the methyl group from a "flavonoid having a methoxy group in the side chain" is sometimes called a "demethylated flavonoid." Similarly, a product produced by removing the methyl group from an "anthocyanidin having a methoxy group in the side chain" is sometimes called a "demethylated anthocyanidin." Similarly, a product produced by removing the methyl group from a "flavan having a methoxy group in the side chain" is sometimes called a "demethylated flavan." Similarly, a product produced by removing the methyl group from a "flavanol having a methoxy group in the side chain" is sometimes called a "demethylated flavanol." Similarly, a product produced by removing the methyl group from a "flavone having a methoxy group in the side chain" is sometimes called a "demethylated flavone." Similarly, a product produced by removing the methyl group from a "flavonol having a methoxy group in the side chain" is sometimes called a "demethylated flavonol." Similarly, a product produced by removing the methyl group from a "flavanone having a methoxy group in the side chain" is sometimes called a "demethylated flavanone." Similarly, a product produced by removing the methyl group from an "isoflavone having a methoxy group in the side chain" is sometimes called a "demethylated isoflavone." Similarly, a product produced by removing the methyl group from a "chalcone having a methoxy group in the side chain" is sometimes called a "demethylated chalcone." Similarly, a product produced by removing the methyl group from a "xanthone having a methoxy group in the side chain" is sometimes called a "demethylated xanthone." Similarly, a product produced by removing the methyl group from a "simple phenol having a methoxy group in the side chain" is sometimes called a "demethylated simple phenol".

[0056] Examples of the demethylated phenolic acid include Caffeic acid is produced by removing the methyl group from one methoxy group of ferulic acid (which has one methoxy group in the side chain). Salicylic acid is produced by removing the methyl group from one methoxy group of anisic acid (which has one methoxy group in the side chain). Protocatechuic acid is produced by removing the methyl group from one methoxy group of vanillic acid (which has one methoxy group in the side chain). Examples include 3-O-methylgallic acid, which is produced by removing the methyl group from one methoxy group of syringic acid (which has two methoxy groups in its side chain), and gallic acid, which is produced by removing the methyl groups from both methoxy groups. Examples of the demethylated lignans include 1,2-Benzenediol is produced by removing the methyl group from one methoxy group of pinoresinol (which has two methoxy groups in the side chain), and 3,3'-bisdemethylpinoresinol is produced by removing the methyl groups from both methoxy groups. Examples include O-demethylsecoisolariciresinol, which is produced by removing the methyl group from one methoxy group of secoisolariciresinol (which has two methoxy groups on the side chain), and dihydroxyenterodiol, which is produced by removing the methyl groups from both methoxy groups. Examples of the demethylated chroman include 6-hydroxychroman produced by removing the methyl group from one methoxy group of 6-methoxychroman (having one methoxy group in the side chain), 2-Hydroxychroman is produced by removing the methyl group from one methoxy group of 2-methoxychroman (having one methoxy group in the side chain). Examples include 5-hydroxychroman, which is produced by removing the methyl group from one methoxy group of 5-methoxychroman (having one methoxy group on the side chain). Examples of the demethylated coumarin include Scopoletin and isoscopoletin are produced by removing the methyl group from one methoxy group of scoparone (which has two methoxy groups in the side chain), and esculetin is produced by removing the methyl groups from both methoxy groups. Esculetin is produced by removing the methyl group from one methoxy group of scopoletin (which has one methoxy group in the side chain). Examples include esculetin, which is produced by removing a methyl group from one methoxy group of isoscopoletin (which has one methoxy group in the side chain). Examples of the demethylated anthocyanidins include Examples include petunidin, which is produced by removing the methyl group from one methoxy group of malvidin (which has two methoxy groups on the side chain), delphinidin, which is produced by removing the methyl group from two methoxy groups, and delphinidin, which is produced by removing the methyl group from one methoxy group of peonidin (which has one methoxy group on the side chain). Examples of the demethylated flavan include 4'-hydroxyflavan is produced by removing the methyl group from one methoxy group of 4'-methoxyflavan (having one methoxy group in the side chain). 3'-hydroxyflavan is produced by removing the methyl group from one methoxy group of 3'-methoxyflavan (having one methoxy group in the side chain). Examples include 7-hydroxyflavan, which is produced by removing the methyl group from one methoxy group of 7-methoxyflavan (having one methoxy group on the side chain). Examples of the demethylated flavanol include Catechin produced by removing the methyl group from one methoxy group of 3'-O-methylcatechin (having one methoxy group in the side chain), Epicatechin is produced by removing the methyl group from one methoxy group of 4'-O-methylepicatechin (having one methoxy group in the side chain). Examples include epigallocatechin, which is produced by removing the methyl group from one methoxy group of 4'-O-methyl epigallocatechin (which has one methoxy group in the side chain). Examples of the demethylated flavones include Among nobiletin (having six methoxy groups in the side chain), 4'-demethylnobiletin is generated by removing the methyl group of one methoxy group, 3',4'-dimethylnobiletin is generated by removing the methyl groups of two methoxy groups, sideritoflavone is generated by removing the methyl groups of three methoxy groups, leucantogenin is generated by removing the methyl groups of four methoxy groups, 2-(3,4-dihydroxyphenyl)-5,6,8-trihydroxy-7-methoxy-4H-1-benzopyran-4-one is generated by removing the methyl groups of five methoxy groups, and vitalgenin is generated by removing the methyl groups of six methoxy groups. Among sinensetin (which has five methoxy groups in the side chain), 4'-desmethylsinensetin is generated by removing the methyl group from one methoxy group, 3',4'-dihydroxy-5,6,7-trimethoxyflavone is generated by removing the methyl groups from two methoxy groups, 3',4',7'-trihydroxy-5,6-dimethylxyflavone is generated by removing the methyl groups from three methoxy groups, carajuflavone is generated by removing the methyl groups from four methoxy groups, and 6-hydroxyluteolin is generated by removing the methyl groups from five methoxy groups. Among tangeretin (which has five methoxy groups in the side chain), 4'-hydroxy-5,6,7,8-tetramethoxyflavone is formed by removing the methyl group from one methoxy group, xanthomicrol is formed by removing the methyl groups from two methoxy groups, isothyrumcin is formed by removing the methyl groups from three methoxy groups, 5,7,8-trihydroxy-2-(4-hydroxyphenyl)-6-methoxy-4H-1-benzopyran-4-one is formed by removing the methyl groups from four methoxy groups, and nortangeretin is formed by removing the methyl groups from five methoxy groups. Examples include norwogonin, which is produced by removing the methyl group from one methoxy group of wogonin (which has one methoxy group in the side chain). Examples of the demethylated flavonol include Quercetagetin is formed by removing the methyl group from one methoxy group of patuletin (which has one methoxy group in the side chain). Quercetin is produced by removing the methyl group from one methoxy group of tamarixetine (which has one methoxy group in the side chain). Laricitrin is produced by removing the methyl group from one methoxy group of syringetin (which has two methoxy groups in its side chain), and myricetin is produced by removing the methyl groups from both methoxy groups. Galangin is produced by removing a methyl group from one methoxy group of isalpinine (which has one methoxy group in the side chain). Examples of the demethylated flavanone include 8-Prenylnaringenin is produced by removing the methyl group from one methoxy group of isoxanthohumol (which has one methoxy group in the side chain). Examples include eriodictyol, which is produced by removing the methyl group from one methoxy group in hesperetin (which has one methoxy group in its side chain). Examples of the demethylated isoflavone include 6-hydroxydaidzein is produced by removing the methyl group from one methoxy group of glycitein (which has one methoxy group in the side chain). Genistein is produced by removing the methyl group from one methoxy group of biochanin (which has one methoxy group in its side chain). Daidzein is produced by removing the methyl group from one methoxy group of formononetin (which has one methoxy group in its side chain). Examples include 6-hydroxygenistein, which is produced by removing the methyl group from one methoxy group of tectorigenin (which has one methoxy group in the side chain). Examples of the demethylated chalcone include Examples include demethylxanthohumol, which is produced by removing the methyl group from one methoxy group of xanthohumol (which has one methoxy group on the side chain). Examples of the demethylated xanthone include γ-mangostin is produced by removing the methyl group from one methoxy group of α-mangostin (which has one methoxy group in the side chain). Examples include α-mangostin, which is produced by removing the methyl group from one methoxy group of β-mangostin (which has two methoxy groups in its side chain), and γ-mangostin, which is produced by removing the methyl groups from both methoxy groups. Examples of the demethylated simple phenols include 4-acetylresorcinol is produced by removing the methyl group from one methoxy group of paeonol (which has one methoxy group in the side chain). An example is phenol produced by removing the methyl group from one methoxy group of anisole (which has one methoxy group on the side chain).

[0057] In one embodiment, the oral composition according to this embodiment is a composition in which methoxy polyphenols and microorganisms are administered in combination. The combination of methoxy polyphenols and microorganisms may be any combination of the above-mentioned "methoxy polyphenols" and "microorganisms". Multiple types of "methoxy polyphenols" and "microorganisms" may be used.

[0058] For example, in one embodiment, the oral composition contains, as a methoxy polyphenol, at least one selected from the group consisting of phenolic acids having a methoxy group in a side chain, lignans having a methoxy group in a side chain, chromans having a methoxy group in a side chain, coumarins having a methoxy group in a side chain, flavonoids having a methoxy group in a side chain, xanthones having a methoxy group in a side chain, and simple phenols having a methoxy group in a side chain, and as a lactic acid bacterium, a strain of the genus Carnobacterium, Enterococcus, Fructobacillus The oral composition is a combination of microorganisms belonging to at least one genus selected from the group consisting of the genera Lactobacillus, Lactococcus, Leuconostoc, Oenococcus, Pediococcus, Sporolactobacillus, Streptococcus, Tetragenococcus, and Weissella. In one embodiment, the oral composition is an oral composition in which at least one methoxypolyphenol selected from the group consisting of isoxanthohumol and xanthohumol is administered in combination with a microorganism belonging to the genus Lactobacillus. In one embodiment, the oral composition is an oral composition in which the methoxy polyphenol is isoxanthohumol and the lactic acid bacterium is Lactobacillus brevis are administered in combination.

[0059] In one embodiment, the oral composition is an oral composition in which isoxanthohumol and enterobacteria are administered in combination. In one embodiment, the oral composition is an oral composition comprising isoxanthohumol and enterobacteria. In one embodiment, the oral composition is an oral composition comprising enterobacteria administered in combination with isoxanthohumol. In one embodiment, the oral composition is an oral composition comprising isoxanthohumol administered in combination with enterobacteria.

[0060] In one embodiment, the oral composition is an oral composition in which methoxy polyphenols and Lactobacillus brevis are administered in combination. In one embodiment, the oral composition is an oral composition comprising methoxy polyphenols and Lactobacillus brevis. In one embodiment, the oral composition is an oral composition comprising Lactobacillus brevis administered in combination with methoxy polyphenols. In one embodiment, the oral composition is an oral composition comprising methoxy polyphenols administered in combination with Lactobacillus brevis.

[0061] In one embodiment, the oral composition is an oral composition in which isoxanthohumol and Lactobacillus brevis are administered in combination. In one embodiment, the oral composition is an oral composition comprising isoxanthohumol and Lactobacillus brevis. In one embodiment, the oral composition is an oral composition comprising Lactobacillus brevis administered in combination with isoxanthohumol. In one embodiment, the oral composition is an oral composition comprising isoxanthohumol administered in combination with Lactobacillus brevis.

[0062] In one embodiment, the oral composition is an oral composition comprising isoxanthohumol and Lactobacillus brevis administered in combination to promote the production of , which is 8-prenylnaringenin, and / or to increase the urinary and / or blood levels of 8-prenylnaringenin in an individual. In one embodiment, the oral composition is an oral composition comprising isoxanthohumol and Lactobacillus brevis to promote the production of , which is 8-prenylnaringenin, and / or to increase the urinary and / or blood levels of 8-prenylnaringenin in an individual. In one embodiment, the oral composition is an oral composition comprising Lactobacillus brevis administered in combination with isoxanthohumol to promote the production of , which is 8-prenylnaringenin, and / or to increase the urinary and / or blood levels of 8-prenylnaringenin in an individual. In one embodiment, the oral composition is an oral composition comprising isoxanthohumol administered in combination with Lactobacillus brevis to promote production of 8-prenylnaringenin and / or to increase urinary and / or blood levels of 8-prenylnaringenin in an individual.

[0063] (Application) As described above in the "microorganism" section, the microorganism in this embodiment is a microorganism that can promote demethylation of methoxy polyphenol in an individual. Therefore, when a substance other than the microorganism causes the elimination of a methyl group from a methoxy group of a methoxy polyphenol in an individual, the elimination of the methyl group by the substance other than the microorganism can be promoted by administering a combination of methoxy polyphenol and a microorganism to the individual. In one embodiment, the oral composition is an oral composition for promoting demethylation of methoxypolyphenols in an individual.

[0064] In one embodiment, the oral composition is for administration in combination with a methoxy polyphenol to promote demethylation of a methoxy polyphenol in an individual, to promote production of demethylated polyphenol in an individual, and / or to increase urinary and / or blood levels of demethylated polyphenol in an individual. In one embodiment, the oral composition is for administration in combination with a microorganism to promote demethylation of methoxy polyphenols in an individual, to promote production of demethylated polyphenols in an individual, and / or to increase urinary and / or blood levels of demethylated polyphenols in an individual.

[0065] The individual is preferably a human or a non-human mammalian individual as described above, and the promotion of demethylation of methoxy polyphenols "in an individual (or within an individual)" is preferably the promotion of demethylation of methoxy polyphenols in the intestine of a mammalian individual. This is because it has been reported that methoxy polyphenols are demethylated by intestinal bacteria present in the intestine of mammals such as humans. Here, the intestine may be either the small intestine (including the jejunum and ileum) or the large intestine (including the colon and rectum), or both, and may be a tissue in which a substance (preferably an intestinal bacterium) having an activity of removing a methyl group from the methoxy group of methoxy polyphenols is present and demethylation of the methyl group occurs. It is presumed that when a combination of methoxy polyphenols and a microorganism is administered and the tissue reaches a tissue in which a substance having the activity of removing the methyl group is present, removal of the methyl group from the methoxy group of the administered methoxy polyphenol occurs, and the removal of the methyl group is promoted by the administered microorganism. It is known that the genus Blautia, which is a major demethylating bacterium in the intestine, is commonly distributed in the intestines of humans and other animals.

[0066] As described above, the oral composition according to this embodiment can be used to promote the demethylation of methoxy polyphenols in an individual, and therefore can be used to promote the production of demethylated polyphenols in an individual to which the oral composition is administered. It is also presumed that the demethylated polyphenols thus produced are absorbed into the body from the intestine, enter the bloodstream, and then excreted in urine. Therefore, the oral composition according to this embodiment can be used to increase the blood concentration of demethylated polyphenols in an individual to which the oral composition is administered, and / or increase the urinary concentration. In one embodiment, the oral composition according to the present invention is an oral composition for enhancing the production of demethylated polyphenols in an individual and / or for increasing the urinary and / or blood levels of demethylated polyphenols in an individual.

[0067] As described above, the oral composition according to the present embodiment, in which a methoxy polyphenol and a microorganism are administered in combination, can be used to promote demethylation of methoxy polyphenols in an individual, and / or can be used to increase the blood and / or urinary concentration of demethylated polyphenols in an individual to whom the oral composition is administered.

[0068] Thus, in one embodiment, the combination of methoxy polyphenols and microorganisms can be used to promote demethylation of methoxy polyphenols in an individual, promote production of demethylated polyphenols in an individual, and / or increase urinary and / or blood levels of demethylated polyphenols in an individual. In one embodiment, the microorganisms can be used in combination with methoxy polyphenols to promote demethylation of methoxy polyphenols in an individual, promote production of demethylated polyphenols in an individual, and / or increase urinary and / or blood levels of demethylated polyphenols in an individual. In one embodiment, methoxy polyphenols can be used in combination with a microorganism to promote demethylation of methoxy polyphenols in an individual, promote production of demethylated polyphenols in an individual, and / or increase urinary and / or blood levels of demethylated polyphenols in an individual.

[0069] In one embodiment, a method for promoting demethylation of methoxy polyphenols in an individual, promoting production of demethylated polyphenols in an individual, and / or increasing urinary and / or blood levels of demethylated polyphenols in an individual comprises administering a methoxy polyphenol and a microorganism to the individual.

[0070] As described above, when a substance other than a microorganism causes the elimination of a methyl group from a methoxy group of a methoxy polyphenol in an individual, the elimination of the methyl group by the substance other than a microorganism can be promoted by administering a combination of a methoxy polyphenol and a microorganism to an individual. The effect of promoting the demethylation of a methoxy polyphenol can be obtained by simultaneously presenting a methoxy polyphenol and a microorganism in an individual for any time.

[0071] Therefore, the methoxy polyphenol and the microorganism may be administered simultaneously, separately, or sequentially, and either the methoxy polyphenol or the microorganism may be administered first. However, it is preferable that the methoxy polyphenol and the microorganism are administered to an individual at a timing that allows them to be present simultaneously in the intestine of the individual for any period of time. The timing of administration of methoxy polyphenols and microorganisms can be appropriately determined by a person skilled in the art based on the animal species, age, weight, disease, etc. of the subject individual, the administration route, the formulation form, etc., and is not limited as long as the desired effect of promoting demethylation of methoxy polyphenols in the individual is obtained. For example, either methoxy polyphenols or microorganisms may be administered within 24 hours after the other is administered, or within 12 hours after the other is administered, or within 6 hours after the other is administered, or within 3 hours after the other is administered, or within 1 hour after the other is administered, or within 30 minutes after the other is administered, or they may be administered simultaneously.

[0072] The oral composition according to this embodiment is administered to an individual in need thereof, preferably orally in the form of a food or pharmaceutical. In one embodiment, the oral composition is a food composition or a pharmaceutical composition. The food composition may contain the active ingredient isoxanthohumol and the microorganism, or a processed product thereof, either as is or in combination with other edible ingredients. Edible ingredients include, in addition to general foods and beverages, for example, compositions or ingredients contained in nutritional foods and beverages, luxury foods and beverages, nutritional supplements and nutritional supplement drinks (supplements), and food additives. Pharmaceutical compositions include, for example, compositions used in medical drugs, over-the-counter drugs, or quasi-drugs. The food compositions and pharmaceutical compositions may be intended for human or non-human animals. Oral administration includes oral ingestion of food.

[0073] ==Second embodiment (food, medicine)== The food and medicine according to this embodiment are a food containing the food composition according to the first embodiment, and a medicine containing the pharmaceutical composition according to the first embodiment, respectively.

[0074] The dosage, frequency of administration, and examples and preferred examples of subjects of administration of the food and medicine are the same as those described in the first embodiment, and can be appropriately determined taking into consideration the content of the oral composition contained in the food or medicine, and the content of the methylated polyphenol and / or microorganism contained in the oral composition. Oral administration includes oral ingestion of food.

[0075] According to the oral composition of the first embodiment, demethylation of methoxy polyphenols in an individual is promoted, and production of demethylated polyphenols can be promoted. For example, demethylated polyphenols obtained by demethylating methoxy polyphenols include compounds having estrogen-like activity. For example, 8-prenylnaringenin having estrogen-like activity is produced by demethylating isoxanthohumol. Therefore, the oral composition according to the first embodiment can be used for the prevention, improvement, and / or treatment of symptoms or diseases caused by estrogen deficiency in an individual. The food according to the present embodiment can be used for the prevention and / or improvement of symptoms or diseases caused by estrogen deficiency, and the medicine according to the present embodiment can be used for the prevention and / or treatment of symptoms or diseases caused by estrogen deficiency. Here, "improvement" and "treatment" include reduction, alleviation, and relief of symptoms of a disease, and "prevention" includes protection against the onset of a disease or symptom in the future and inhibition of its progression.

[0076] Examples of symptoms or diseases caused by estrogen deficiency include vague symptoms associated with the menstrual cycle, urogenital disorders such as atrophic vaginitis, osteoporosis, arteriosclerosis, memory disorders, Alzheimer's disease, thrombotic diseases, rough skin, obesity, and muscle atrophy (e.g., disuse muscle atrophy).

[0077] (food) In one embodiment, the food is a functional food. As described in the first embodiment, the food composition according to the first embodiment is a food composition having a function of promoting demethylation of methoxy polyphenols in an individual who ingests the food containing the food composition. In Japan, examples of functional foods include general foods, which include nutritional supplements, health supplements, and nutritionally adjusted foods, as well as health functional foods (which include nutritional functional foods, foods for specified health uses (Tokuho), and foods with functional claims), which are labeled according to the safety and effectiveness standards set by the government.

[0078] The food composition according to the first embodiment may be prepared so that the methoxy polyphenols and microorganisms contained therein are contained in a single food product, and the methoxy polyphenols and microorganisms are administered simultaneously to an individual by ingesting the food product; alternatively, the methoxy polyphenols and the microorganisms may be contained in separate foods, and the methoxy polyphenols and microorganisms may be administered to an individual by ingesting two or more foods simultaneously, separately, or successively.

[0079] The form of the food is not limited, but since the oral composition is administered to an individual and used to promote the demethylation reaction of methoxy polyphenols in the intestine, it is preferable that the food be in the form of a food that can be transferred to the intestine. From the viewpoint of being able to transfer to the intestine, it may be directly administered to the intestine from the nasal cavity or the like using a tube, but from the viewpoint of ease of administration, it is preferable that the food be in the form suitable for oral administration.

[0080] When formulated as two or more foods, the individual foods can be administered simultaneously, separately at a fixed time interval, or consecutively. The two or more foods can also be administered at different times each day. When formulated as two or more foods, the individual foods can also be administered by different routes. The food composition may be prepared as a food so that the dosage described in the first embodiment can be administered to an individual, and the dosage per administration may be one food or two or more foods.

[0081] The food composition can be prepared in the form of a desired food or drink (collectively referred to as "food") by combining methoxy polyphenols and microorganisms, or processed products thereof, either as is or with other food or drink ingredients, additives, one or more food compositions, etc. Examples of such food or drink include general food and drink, as well as foods with health claims (including foods for specified health uses, foods with nutritional functions, supplements, etc.), foods for the sick, etc. The form of these foods and beverages is not particularly limited, but specific examples include supplements such as capsules (soft capsules, hard capsules), tablets, granules, powders, and jellies, beverages such as tea drinks, nutritional drinks, fruit juice drinks, carbonated drinks, and lactic acid drinks, and luxury items such as gummies, candies, and jellies. The foods and beverages may be general foods such as soups, processed meat products, processed vegetable products, processed fruit products, seasonings, and concentrated foods. Here, processed products refer to natural ingredients that have been processed and / or cooked, and include frozen foods, retort foods, canned foods, bottled foods, and the like.

[0082] The food may contain a food composition containing a functional ingredient in addition to the food composition according to the first embodiment. The functional ingredient is not limited to any ingredient that is desired to be ingested in addition to a normal diet, but is preferably a substance that can exert some nutritional or physiological activity or effect that is the use or purpose of the food containing the food composition in a subject who ingests it.

[0083] (Medicine) The pharmaceutical composition according to the first embodiment may be prepared such that the methoxy polyphenol and the microorganism contained therein are formulated into a single drug, and the methoxy polyphenol and the microorganism are administered simultaneously to an individual by administering the drug, or the methoxy polyphenol and the microorganism may be formulated into separate drugs, and the two or more drugs may be administered simultaneously, separately, or successively to an individual, thereby administering the methoxy polyphenol and the microorganism. The pharmaceutical composition may be formulated as a medicine so that it can be administered to an individual in the dosage amount described in the first embodiment, and the dosage amount per administration may be one drug or two or more drugs.

[0084] The form of the medicine is not limited, but since the oral composition is administered to an individual and used to promote the demethylation reaction of methoxy polyphenols in the intestine, it is preferable that the medicine is in a form that can be transferred into the intestine. The medicine can be, for example, a tablet, granule, powder, capsule, emulsion, suspension, syrup, or an injection such as a sterile solution or suspension. From the viewpoint of being able to transfer into the intestine, it may be directly administered from the nasal cavity or the like using a tube or the like, but from the viewpoint of ease of administration, it is preferable that the medicine is in a form suitable for oral administration.

[0085] When a drug is prepared as two or more formulations, the individual formulations can be administered simultaneously, separately at a certain time interval, or consecutively. The two or more formulations can also be administered at different times each day. When a drug is prepared as two or more formulations, the individual formulations can also be administered by different routes.

[0086] A non-limiting list of exemplary embodiments and combinations of exemplary embodiments of the present disclosure are disclosed below. [1] An oral composition in which methoxypolyphenols and enterobacteria are administered in combination. [2] An oral composition comprising methoxypolyphenols and enterobacteria. [3] An oral composition comprising enterobacteria administered in combination with methoxypolyphenols. [4] An oral composition comprising methoxypolyphenols administered in combination with enterobacteria. [5] The oral composition according to any one of [1] to [4], wherein the methoxypolyphenol and the enterobacteria are administered simultaneously, separately or sequentially. [6] An oral composition described in any one of [1] to [5] for promoting demethylation of methoxypolyphenols in an individual. [7] The oral composition according to any one of [1] to [6] for promoting production of demethylated polyphenols in an individual and / or for increasing urinary and / or blood concentrations of demethylated polyphenols in an individual. [8] The oral composition according to any one of [1] to [7], wherein the methoxypolyphenol is at least one selected from the group consisting of phenolic acids having a methoxy group in their side chains, lignans having a methoxy group in their side chains, chromans having a methoxy group in their side chains, coumarins having a methoxy group in their side chains, flavonoids having a methoxy group in their side chains, xanthones having a methoxy group in their side chains, and simple phenols having a methoxy group in their side chains. [9] The oral composition described in [8], wherein the methoxy polyphenol is a flavonoid having a methoxy group in the side chain.

[10] The oral composition described in [9], wherein the flavonoid having a methoxy group in a side chain is at least one selected from the group consisting of a flavanone having a methoxy group in a side chain and a chalcone having a methoxy group in a side chain.

[11] The oral composition described in [9], wherein the flavonoid having a methoxy group in its side chain is at least one selected from the group consisting of isoxanthohumol and xanthohumol.

[12] The oral composition described in any one of claims [1] to

[11] , wherein the methoxypolyphenol is derived from a plant.

[13] The oral composition described in

[12] , wherein the plant is hops or watermelon.

[14] The oral composition according to any one of [1] to

[13] , wherein the intestinal bacteria is lactic acid bacteria or bifidobacteria.

[15] The oral composition described in

[14] , wherein the lactic acid bacteria are microorganisms belonging to at least one genus selected from the group consisting of the genera Carnobacterium, Enterococcus, Fructobacillus, Lactobacillus, Lactococcus, Leuconostoc, Oenococcus, Pediococcus, Sporolactobacillus, Streptococcus, Tetragenococcus, and Weissella.

[16] The oral composition described in

[15] , wherein the lactic acid bacterium is Lactobacillus brevis.

[17] Methoxypolyphenols at 0.1–100 mg / day and intestinal bacteria at 1×10 8 From 10×10 12 The oral composition according to any one of [1] to

[16] , wherein the composition is administered at a dose of 100 cfu / day.

[18] An oral composition described in any one of [1] to

[17] , which is a food or pharmaceutical composition.

[19] A functional food comprising the food composition described in

[18] .

[20] A functional food described in

[19] for preventing and / or improving symptoms caused by estrogen deficiency.

[21] A pharmaceutical comprising the pharmaceutical composition described in

[18] .

[22] The pharmaceutical agent described in

[21] for preventing and / or treating symptoms caused by estrogen deficiency.

[0087] [2-1] Use of methoxypolyphenols and enterobacteria for producing an oral composition. [2-2] Use of enterobacteria for the manufacture of an oral composition to be administered in combination with methoxypolyphenols. [2-3] Use of methoxypolyphenols for the manufacture of an oral composition to be administered in combination with enterobacteria. [2-4] The use according to any one of [2-1] to [2-3], wherein the methoxypolyphenol and the enterobacteria are administered simultaneously, separately or sequentially. [2-5] The use described in any one of [2-1] to [2-4], wherein the oral composition is an oral composition described in any one of [6] to

[17] . [2-6] The use according to any one of [2-1] to [2-5], wherein the oral composition is a food or pharmaceutical composition. [2-7] The use described in any one of [2-1] to [2-6], wherein the oral composition is a composition used for producing a functional food for preventing and / or improving symptoms caused by estrogen deficiency. [2-8] The use described in any one of [2-1] to [2-6], wherein the oral composition is a composition used for producing a medicine for preventing and / or treating symptoms caused by estrogen deficiency.

[0088] [3-1] A combination of methoxypolyphenols and intestinal bacteria for use in promoting the demethylation of methoxypolyphenols in an individual. [3-2] A combination of methoxy polyphenols and intestinal bacteria for use in promoting the production of demethylated polyphenols in an individual and / or for use in increasing urinary and / or blood concentrations of demethylated polyphenols in an individual. [3-3] An enterobacteria used in combination with methoxypolyphenols for use in promoting the demethylation of methoxypolyphenols in an individual. [3-4] Methoxypolyphenols, used in combination with gut bacteria, for use in promoting the demethylation of methoxypolyphenols in individuals. [3-5] An enterobacteria in combination with methoxypolyphenols for use in promoting the production of demethylated polyphenols in an individual and / or for use in increasing urinary and / or blood levels of demethylated polyphenols in an individual. [3-6] A methoxypolyphenol in combination with gut bacteria for use in promoting the production of demethylated polyphenols in an individual and / or for use in increasing urinary and / or blood levels of demethylated polyphenols in an individual. [3-7] A combination, enterobacteria, or methoxypolyphenol described in any one of [3-1] to [3-6], wherein the methoxypolyphenol and the enterobacteria are administered simultaneously, separately, or sequentially. [3-8] The combination, enterobacteria, or methoxypolyphenol described in any one of [3-1] to [3-7], wherein the methoxypolyphenol is at least one selected from the group consisting of phenolic acids having a methoxy group in their side chains, lignans having a methoxy group in their side chains, chromans having a methoxy group in their side chains, coumarins having a methoxy group in their side chains, flavonoids having a methoxy group in their side chains, xanthones having a methoxy group in their side chains, and simple phenols having a methoxy group in their side chains. [3-9] The combination, enterobacteria, or methoxypolyphenol described in [3-8], wherein the methoxypolyphenol is a flavonoid having a methoxy group in the side chain. [3-10] The combination, enterobacteria, or methoxypolyphenol described in [3-9], wherein the flavonoid having a methoxy group in its side chain is at least one selected from the group consisting of a flavanone having a methoxy group in its side chain and a chalcone having a methoxy group in its side chain. [3-11] The combination, enterobacteria, or methoxypolyphenol described in [3-9], wherein the flavonoid having a methoxy group in its side chain is at least one selected from the group consisting of isoxanthohumol and xanthohumol. [3-12] A combination, enterobacteria, or methoxypolyphenol described in any one of [3-1] to [3-11], wherein the methoxypolyphenol is derived from a plant. [3-13] The combination, enterobacteria, or methoxypolyphenols described in [3-12], wherein the plant is hops or watermelon. [3-14] A combination, enterobacteria, or methoxypolyphenol described in any one of [3-1] to [3-13], wherein the enterobacteria are lactic acid bacteria or bifidobacteria. [3-15] The combination, enterobacteria, or methoxypolyphenol described in [3-14], wherein the lactic acid bacteria is a microorganism belonging to at least one genus selected from the group consisting of the genera Carnobacterium, Enterococcus, Fructobacillus, Lactobacillus, Lactococcus, Leuconostoc, Oenococcus, Pediococcus, Sporolactobacillus, Streptococcus, Tetragenococcus, and Weissella. [3-16] The combination described in [3-15], wherein the lactic acid bacteria is Lactobacillus brevis, enterobacteria, or methoxypolyphenols. [3-17] Methoxypolyphenols at 0.1-100 mg / day and intestinal bacteria at 1×10 8 From 10×10 12 The combination, enterobacteria, or methoxypolyphenol described in any one of [3-1] to [3-16] is administered at a dose of 100 cfu / day. [3-18] A combination described in any one of [3-1] to [3-17], enterobacteria, or methoxypolyphenols for use in preventing and / or improving symptoms caused by estrogen deficiency. [3-19] A combination described in any one of [3-1] to [3-17], enterobacteria, or methoxypolyphenols for use in preventing and / or treating symptoms caused by estrogen deficiency.

[0089] [4-1] A method for promoting demethylation of methoxypolyphenols in an individual, comprising administering a methoxypolyphenol and an intestinal bacterium to the individual. [4-2] A method for promoting production of demethylated polyphenols in an individual and / or increasing urinary and / or blood concentrations of demethylated polyphenols in an individual, comprising administering to the individual a methoxy polyphenol and an intestinal bacterium. [4-3] The method according to [4-1] or [4-2], wherein the methoxypolyphenol and the enterobacteria are administered simultaneously, separately or sequentially. [4-4] The method according to any one of [4-1] to [4-3], wherein the methoxy polyphenol is at least one selected from the group consisting of phenolic acids having a methoxy group in their side chains, lignans having a methoxy group in their side chains, chromans having a methoxy group in their side chains, coumarins having a methoxy group in their side chains, flavonoids having a methoxy group in their side chains, xanthones having a methoxy group in their side chains, and simple phenols having a methoxy group in their side chains. [4-5] The method according to [4-4], wherein the methoxy polyphenol is a flavonoid having a methoxy group in the side chain. [4-6] The method according to [4-5], wherein the flavonoid having a methoxy group in a side chain is at least one selected from the group consisting of a flavanone having a methoxy group in a side chain and a chalcone having a methoxy group in a side chain. [4-7] The method according to [4-6], wherein the flavonoid having a methoxy group in its side chain is at least one selected from the group consisting of isoxanthohumol and xanthohumol. [4-8] The method according to any one of [4-1] to [4-7], wherein the methoxypolyphenol is derived from a plant. [4-9] The method according to [4-8], wherein the plant is hops or watermelon. [4-10] The method according to any one of [4-1] to [4-9], wherein the intestinal bacteria are lactic acid bacteria or bifidobacteria. [4-11] The method according to [4-10], wherein the lactic acid bacteria are microorganisms belonging to at least one genus selected from the group consisting of the genera Carnobacterium, Enterococcus, Fructobacillus, Lactobacillus, Lactococcus, Leuconostoc, Oenococcus, Pediococcus, Sporolactobacillus, Streptococcus, Tetragenococcus, and Weissella. [4-12] The method according to [4-11], wherein the lactic acid bacterium is Lactobacillus brevis. [4-13] Methoxypolyphenols at 0.1-100 mg / day and intestinal bacteria at 1×10 8 From 10×10 12 The method according to any one of [4-1] to [4-12], wherein the cfu / day is administered. [4-14] A method according to any one of [4-1] to [4-13] for preventing and / or improving symptoms caused by estrogen deficiency. [4-15] A method according to any one of [4-1] to [4-14] for preventing and / or treating symptoms caused by estrogen deficiency. EXAMPLES

[0090] The present disclosure will be described in more detail below by showing examples, but interpretation of the present disclosure is not limited to these examples.

[0091] [Example 1] Test to confirm the effect of lactic acid bacteria in promoting 8-prenylnaringenin production A predetermined amount of isoxanthohumol (Fujifilm Wako Pure Chemical Industries, Ltd.) and lactic acid bacteria Lactobacillus brevis (high concentration Lactobacillus brevis) (Seti Pharmaceuticals, Inc.) were suspended in a 0.5% solution of sodium carboxymethylcellulose (Kanto Chemical Co., Ltd.) to prepare a mixed solution of isoxanthohumol and lactic acid bacteria for forced oral administration. The basal diet used was AIN-93M (Oriental Yeast Co., Ltd.). Groups of 6 11-week-old female SD rats (SPF, CLEA Japan) were allowed to acclimate for one week with free access to basal diet AIN-93M and water. The end of the acclimatization period was designated day 0, and the mixed solution of isoxanthohumol and lactic acid bacteria prepared above was administered orally for 14 days to each group. A solution containing only isoxanthohumol was administered orally for 14 days to the control group. Even during the administration period, the rats were allowed to freely consume basal diet and water.

[0092] The experimental groups were (1) a control group (administered only isoxanthohumol (IX)), (2) a low-dose lactobacillus-administered group (isoxanthohumol 8 mg / rat / day and lactobacillus 8 × 10 8 cfu / rat / day), (3) high-dose lactobacillus administration group (isoxanthohumol 8 mg / rat / day and lactobacillus 8 × 10 9 The rats were administered for 14 consecutive days, and urine samples (24 hours) were collected four times: before administration, 4 days after administration, 8 days after administration, and after the end of the entire administration period. After urine collection was completed 14 days after administration, blood was collected from the posterior vena cava of all rats to obtain plasma.

[0093] Quantitative analysis of 8-prenylnaringenin in rat urine and plasma was performed by deconjugating conjugated 8-prenylnaringenin present in urine and plasma with β-glucuronidase and arylsulfatase, followed by measurement using HPLC. 0.6 U of β-glucuronidase and 1.2 U of arylsulfatase were added to 0.5 mL of urine and plasma, and incubated at 37°C for 16 hours to liberate 8-prenylnaringenin, which was then extracted with 1 mL of ethyl acetate and measured using HPLC.

[0094] The results of urine sample analysis are shown in Figure 1. The 8-prenylnaringenin content was calculated for each individual from the HPLC analysis value and the collected urine volume. Compared to the control group administered only isoxanthohumol, the amount of 8-prenylnaringenin produced increased in both the low-dose lactobacillus group and the high-dose lactobacillus group, both of which were administered in combination with lactobacillus. Furthermore, the amount of 8-prenylnaringenin produced tended to increase with the administration of a higher dose of lactobacillus. The analysis results of the plasma samples are shown in Figure 2. Compared to the control group administered only isoxanthohumol, the plasma 8-prenylnaringenin concentration did not change in the group administered a low dose of lactic acid bacteria, but the amount of 8-prenylnaringenin produced increased significantly in the group administered a high dose of lactic acid bacteria.

[0095] The results of this example demonstrated that administration of isoxanthohumol in combination with lactic acid bacteria promoted the conversion of isoxanthohumol to 8-prenylnaringenin in the body by the lactic acid bacteria.

[0096] [Example 2] Confirmation of the effect of lactic acid bacteria in promoting 8-prenylnaringenin production in the same rat A certain amount of isoxanthohumol (Fujifilm Wako Pure Chemical Industries, Ltd.) and lactobacillus brevis (high-concentration Lactobacillus brevis) (Seti Pharmaceuticals, Inc.) were suspended in a 0.5% solution of sodium carboxymethylcellulose (Kanto Chemical Co., Ltd.) to prepare an isoxanthohumol solution and a mixed solution of isoxanthohumol and lactobacillus for forced oral administration. AIN-93M (Oriental Yeast Co., Ltd.) was used as the basal feed. Twenty-four 10-week-old female SD rats (SPF, CLEA Japan, Inc.) were allowed to freely consume basal feed AIN-93M and water for one week for acclimation. The end of acclimation was designated as day 0, and the isoxanthohumol solution prepared above was administered orally for 14 days. The administration of the isoxanthohumol solution was suspended for five days from the day after the 14th day of administration, and the 5th day after the suspension of administration was designated as day 0, and the isoxanthohumol and lactic acid bacteria mixed solution prepared above was administered for 14 days. Even during the administration period, the rats were allowed to freely consume basal feed and water.

[0097] The experimental systems were: (1) isoxanthohumol administration period (isoxanthohumol 8 mg / rat / day), (2) isoxanthohumol and lactic acid bacteria administration period (isoxanthohumol 8 mg / rat / day and lactic acid bacteria 8 × 10 9 cfu / rat / day) was set. Each administration period was 14 days, and urine (24 hours) was collected six times throughout the entire period: before administration, 8 days after administration, and 15 days after administration. In addition, (1) blood was collected from the jugular vein after urine collection on the 14th day after administration in the isoxanthohumol administration period, and (2) blood was collected from the posterior vena cava in all animals after urine collection on the 14th day after administration in the isoxanthohumol and lactic acid bacteria administration period, and plasma was obtained from each.

[0098] Quantitative analysis of 8-prenylnaringenin in rat urine and plasma was performed by deconjugating conjugated 8-prenylnaringenin present in urine and plasma with β-glucuronidase and arylsulfatase, followed by measurement using HPLC. 0.6 U of β-glucuronidase and 1.2 U of arylsulfatase were added to 0.5 mL of urine and plasma, and incubated at 37°C for 16 hours to liberate 8-prenylnaringenin, which was then extracted with 1 mL of ethyl acetate and measured using HPLC.

[0099] The analysis results of 8-prenylnaringenin in plasma are shown in Figure 3. When comparing the 14th day after administration of the isoxanthohumol solution with the 14th day after administration of the mixed solution of isoxanthohumol and lactic acid bacteria, the plasma 8-prenylnaringenin concentration was significantly increased by simultaneous administration of lactic acid bacteria (in the figure, * indicates p<0.05).

[0100] Furthermore, based on the plasma concentration of 8-prenylnaringenin on the 14th day after administration of the isoxanthohumol solution, the mice were divided into groups with low productivity (0.06μM~0.22μM), intermediate productivity (0.23μM~0.52μM), and high productivity (0.58μM~1.8μM) for analysis. The analysis results are shown in Figure 4. The analysis showed that the 8-prenylnaringenin concentration increased significantly with the co-administration of lactic acid bacteria, especially in the low-productivity group (** indicates p<0.01). In the intermediate and high-productivity groups, no significant increase in 8-prenylnaringenin concentration was observed with the co-administration of lactic acid bacteria.

[0101] Similarly, urinary 8-prenylnaringenin was analyzed by dividing it into three groups: low productivity group (0.0017μM-0.0066μM), intermediate productivity group (0.0069μM-0.01μM), and high productivity group (0.013μM-0.046μM). The analysis results are shown in Figure 5. The analysis showed that 8-prenylnaringenin concentrations increased significantly with co-administration of lactic acid bacteria, especially in the low-productivity group (in the figure, * indicates p<0.05). In the intermediate and high-productivity groups, no significant increase in 8-prenylnaringenin concentrations was observed with co-administration of lactic acid bacteria.

[0102] The results of this example demonstrated that administration of isoxanthohumol in combination with lactic acid bacteria promoted the conversion of isoxanthohumol to 8-prenylnaringenin in the body by the lactic acid bacteria. It is known that 8-prenylnaringenin-producing bacteria are mainly localized in the large intestine, while endogenous lactic acid bacteria are localized in the small intestine, and they are unlikely to interact directly in the intestine. However, since the administered lactic acid bacteria do not colonize the small intestine but flow to the large intestine, it is presumed that by administering isoxanthohumol in combination with lactic acid bacteria, the 8-prenylnaringenin-producing bacteria and lactic acid bacteria interact with each other, resulting in the promotion of 8-prenylnaringenin production. Furthermore, in the low-productivity group, where 8-prenylnaringenin production was low when isoxanthohumol alone was administered, it was shown that 8-prenylnaringenin production was significantly increased by administering a combination of isoxanthohumol and lactic acid bacteria. It is presumed that individuals capable of high production of 8-prenylnaringenin by administration of only isoxanthohumol already have an intestinal environment that is conducive to the production of 8-prenylnaringenin, and therefore it is difficult to obtain the effect of promoting 8-prenylnaringenin production by the administered lactic acid bacteria.

Claims

1. An oral composition in which methoxy polyphenols and enterobacteria are administered in combination.

2. An oral composition comprising methoxypolyphenols and enterobacteria.

3. An oral composition comprising enterobacteria administered in combination with methoxypolyphenols.

4. An oral composition comprising methoxypolyphenols administered in combination with enterobacteria.

5. 5. An oral composition according to claim 1 for promoting demethylation of methoxypolyphenols in an individual.

6. 5. An oral composition according to claim 1 for promoting the production of demethylated polyphenols in an individual and / or for increasing the urinary and / or blood concentration of demethylated polyphenols in an individual.

7. The oral composition according to any one of claims 1 to 4, wherein the methoxy polyphenol is at least one selected from the group consisting of phenolic acids having a methoxy group in a side chain, lignans having a methoxy group in a side chain, chromans having a methoxy group in a side chain, coumarins having a methoxy group in a side chain, flavonoids having a methoxy group in a side chain, xanthones having a methoxy group in a side chain, and simple phenols having a methoxy group in a side chain.

8. The oral composition according to claim 7, wherein the methoxy polyphenol is a flavonoid having a methoxy group in the side chain.

9. The oral composition according to claim 8, wherein the flavonoid having a methoxy group in a side chain is at least one selected from the group consisting of a flavanone having a methoxy group in a side chain and a chalcone having a methoxy group in a side chain.

10. The oral composition according to claim 9, wherein the flavonoid having a methoxy group in a side chain is at least one selected from the group consisting of isoxanthohumol and xanthohumol.

11. 5. The oral composition according to any one of claims 1 to 4, wherein the intestinal bacteria is a lactic acid bacterium or a bifidobacterium.

12. The oral composition according to claim 11, wherein the lactic acid bacteria is a microorganism belonging to at least one genus selected from the group consisting of the genera Carnobacterium, Enterococcus, Fructobacillus, Lactobacillus, Lactococcus, Leuconostoc, Oenococcus, Pediococcus, Sporolactobacillus, Streptococcus, Tetragenococcus, and Weissella.

13. The oral composition according to claim 12, wherein the lactic acid bacterium is Lactobacillus brevis.

14. Methoxypolyphenols: 0.1-100 mg / day; intestinal bacteria: 1 x 10 ８ From 10 x 10 １２ 5. The oral composition of claim 1, wherein the oral composition is administered in units of cfu / day.

15. 5. The oral composition according to claim 1, which is a food or pharmaceutical composition.

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