JP2020074695A - Composition for promoting proliferation of genus coprococcus bacterium - Google Patents

Abstract

To provide a composition for promoting the proliferation of genus Coprococcus bacterium in an intestinal flora.SOLUTION: There is provided a composition for promoting the proliferation of genus Coprococcus bacterium in an intestinal flora which contains D-psicose as an active ingredient. The composition of the present invention can be made for oral ingestion, and furthermore, can be made to contain an effective intake amount of D-psicose for human per day. The composition of the present invention can be used for treatment, prevention or improvement of a disease or a symptom which can be treated, prevented or improved by the proliferation acceleration of genus Coprococcus bacterium in an intestinal flora.SELECTED DRAWING: None

Description

  The present invention relates to a composition for promoting the growth of Coprococcus spp. In the intestinal flora.

  It is known that the intestinal microbiota is closely related to human health and diseases, and in particular, it is known that the environment of the human intestinal microbiota greatly changes due to aging and stress. Therefore, by adjusting the intestinal environment, it is possible to reduce the risk of developing infectious diseases due to stress, and to improve obesity, cancer, diabetes, liver disease, autoimmune disease, deterioration of immune function, etc. ing.

It is said that 100 to more than 100 trillion intestinal bacteria inhabit the human intestine, and generally, there are useful microorganisms (useful bacteria) such as bifidobacteria and lactic acid bacteria, and Clostridium perfringens. Such harmful microorganisms (harmful bacteria) live together. In order to maintain the human intestinal environment in a better condition, it is considered important to allow useful intestinal bacteria to exist in the large intestine as a dominant species. Butyric acid-producing bacteria that produce butyric acid in the intestinal tract are known as useful intestinal bacteria other than bifidobacteria and lactic acid bacteria. Among these butyric acid-producing bacteria, bacteria of the genus Coprococcus are dominant bacteria (dominant bacteria) that generally have an occupancy of 5% or more in the human intestinal flora (Non-patent Document 1). It has been confirmed that the intestinal flora of patients with end-stage cirrhosis decreases (Non-patent Document 2).

Scientific Reports. 7, Article number: 14874, 2017 Qin N. et al., Nature. 513 (7516): 59-64, 2014

  It is an object of the present invention to provide a composition for promoting the growth of Coprococcus spp in the intestinal flora and a growth promoter for Coprococcus spp in the intestinal flora.

  The present inventors have now found that orally ingesting D-psicose in human subjects can significantly increase the occupancy of Coprococcus in the intestinal flora. The present invention is based on this finding.

According to the present invention, the following inventions are provided.
[1] A composition for promoting the growth of coprococcus bacteria in the intestinal flora and a growth promoter for coprococcus bacteria in the intestinal flora, comprising D-psicose as an active ingredient.
[2] The composition and agent according to the above [1], which are to be taken orally.
[3] The composition and agent according to the above [1] or [2], which comprises an effective intake amount of D-psicose per day for humans.
[4] The composition and preparation according to any one of [1] to [3] above, wherein the effective daily intake of D-psicose in a human is 1 to 50 g.
[5] The composition and agent according to any one of the above [1] to [4], which is continuously ingested for one week or more.
[6] The composition and agent according to any one of [1] to [5] above, which is in a unit packaging form.
[7] The composition and agent according to any one of [1] to [6] above, which is a food composition.
[8] The use according to any one of [1] to [7] above for use in the treatment, prevention or amelioration of a disease or condition that can be treated, prevented or ameliorated by promoting the growth of Coprococcus spp in the intestinal flora. Compositions and agents.
[9] A composition for improving intestinal flora and an agent for improving intestinal flora, which comprises D-psicose as an active ingredient.
[10] A composition for promoting butyric acid production in the intestine and an agent for promoting butyric acid production in the intestine, which comprises D-psicose as an active ingredient.
[11] A composition comprising D-psicose as an active ingredient for promoting blood sugar and / or lipid metabolism, improving immune function, or promoting digestion and / or absorption, and a blood sugar and / or lipid metabolism promoter , Immune function enhancers, and digestion and / or absorption enhancers.
[12] A composition for treating, preventing or ameliorating a disease or symptom, which comprises D-psicose as an active ingredient and which can be treated, prevented or ameliorated by promoting the growth of Coprococcus spp. Treatment, prevention or amelioration agent for symptoms.
[13] A risk of developing a disease or symptom, which comprises D-psicose as an active ingredient and can be treated, prevented or ameliorated by promoting the growth of coprococcus in the intestinal flora, and / or the risk of worsening intestinal flora. And a reducing agent for the risk of developing a disease or condition that can be treated, prevented or ameliorated by promoting the growth of Coprococcus bacteria in the intestinal flora and / or the risk of worsening the intestinal flora.

  The compositions of the above [1] and [9] to [13] are referred to herein as “the composition of the present invention”, and the agents of the above [1] and [9] to [13] are referred to herein as “the composition of the present invention”. Each of them may be referred to as the "agent of the present invention".

  Since the composition and agent of the present invention utilize D-psicose, which has been used as a rare sugar and have been used as a food, as an active ingredient, it is expected to promote the growth of Coprococcus spp. It is advantageous in that it has few side effects even when ingested and is highly safe.

Detailed explanation of the invention

D-psicose, which is an active ingredient of the composition and agent of the present invention, is one of rare sugars, and is also known as D-allulose or D-ribo-2-hexulose. be called. In the present invention, D-psicose may be purified from a natural product, produced by a fermentation method, produced by an enzymatic method, produced by a chemical synthesis or the like. From the viewpoint of simplicity, those produced by an enzymatic method can be preferably used. The D-psicose used in the present invention may be either completely purified or may contain a small amount of impurities. Examples of D-psicose include those extracted from plants such as duina, those obtained by isomerizing D-glucose and D-fructose with an alkali by the alkali isomerization method (alkali isomerization method), Aspergillus aculeatus, and the like. It is possible to use a product fermented and produced using a filamentous fungus (fermentation method), or a product obtained by isomerizing starch, glucose, fructose or the like with an enzyme such as isomerase or epimerase (enzyme isomerization method), A sugar composition containing D-psicose (for example, syrup, powder product) may be used as it is. As D-psicose, a commercially available product (for example, "Rare Sugar Sweet" manufactured by Matsutani Chemical Co., Ltd., "ASTRAEA" manufactured by Matsutani Chemical Co., Ltd.) can be used.

  The composition and agent of the present invention can be provided as D-psicose as it is, or can be provided by mixing D-psicose with other components. The content of D-psicose in the composition and agent of the present invention can be arbitrarily determined according to the purpose, use, form, dosage form, symptom, weight, etc., but the present invention is not limited thereto. The content (solid content conversion) can be defined as follows with respect to the total amount. That is, the lower limit of the content of D-psicose in the composition and agent of the present invention can be 0.5% by mass, preferably 1% by mass, more preferably 2% by mass, 3% by mass, 4% by mass. % By mass or 5% by mass. The upper limit of the content can be 100% by mass, preferably 99% by mass, more preferably 90% by mass, 80% by mass, 70% by mass or 60% by mass. These lower limit values and upper limit values can be arbitrarily combined, and the content range is, for example, 0.5 to 100% by mass (preferably 1 to 99% by mass, more preferably 2 to 90% by mass or 5 to 60% by mass).

  The content of D-psicose in the composition and agent of the present invention can be measured by a high performance liquid chromatography method (HPLC method).

The composition and agent of the present invention are used for promoting the growth of Coprococcus spp. In the intestinal flora. A bacterium belonging to the genus Coprococcus is one of useful bacteria in the intestine and is a butyric acid-producing bacterium. Here, "promotion of growth of a bacterium of the genus Coprococcus" is used to mean including promotion of increase of a bacterium of the genus Coprococcus. The degree of “promotion of growth of Coprococcus spp.” Can be evaluated using the occupancy rate (%) of the Coprococcus spp. In the intestinal flora as an index (see Examples below). Specifically, when the proportion of the bacterium of the genus Coprococcus in the intestinal flora after ingestion of D-psicose is higher than that of the bacterium of the genus Coprococcus in the intestinal flora before ingestion, preferably D-psicose When the proportion of Coprococcus spp. In the intestinal flora after ingestion exceeds the proportion of Coprococcus spp. In the intestinal flora before ingestion by a significant difference (significance level 5%), or , When the proportion of the genus Coprococcus in the intestinal flora after ingestion of D-psicose is about 1.1 times or more the proportion of the coprococcus in the intestinal flora before ingestion, When it is preferably about 1.2 times or more, more preferably about 1.3 times or more, further preferably 1.4 times or more, particularly preferably 1.5 times or more, and particularly preferably 1.6 times or more. As described above, when it is 1.8 times or more or 2 times or more, it can be determined that the growth of Coprococcus in the intestinal flora is promoted.

  As shown in Examples below, D-psicose has a growth-promoting effect on the intestinal flora of Coprococcus spp., Whereas Coprococcus spp. Is a butyric acid-producing bacterium and increases intestinal butyric acid production. Here, butyric acid is a major energy source that is preferentially consumed in colonic epithelial cells, and it promotes the activation of epithelial cells and the growth of normal colonic epithelial cells. Physiological functions such as promotion of digestion, improvement of immune function by normalization of intestinal mucosa, promotion of digestion and absorption by improvement of intestinal function are brought about. Increased production of butyric acid in the intestine also reduces the pH in the colon (as well as decreased solubility of bile salts, improved mineral absorption, suppression of ammonia absorption, suppression of pathogenic microorganisms), colonic vein and hepatic hilum. Blood circulation promotion, colon cancer cell growth suppression and apoptosis induction, protection against colon cancer and colitis, anti-inflammatory effect, water and sodium absorption promotion, ion and fluid absorption promotion, diarrhea suppression, colon Oxidative stress in the body, suppression of obesity by promoting satiety, improvement of intestinal barrier function (further promotion of mucin layer formation, promotion of secretion of antimicrobial peptide / tight junction constituent proteins), suppression of leaky gut syndrome (LGS), etc. It is known to bring about various physiological functions of (for example, Gijs den Besten et al., Journal of lipid research, jlr-R036012, 2013, Tan Jian et al., Advances in immunology 121: 91-119, 2014. , T. Sakata and H. Ichikawa, Journal of Japan Oil Chemists' Society 46 (10): 1205-1212, 1997, Topping, Asia Pacific J Clin Nutr. 5 (1): 15-19, 1996 and Riviere et.al. ., Leroy F1, De Vuyst L1., Front Microbiol. 7: 979, 2016). Therefore, the composition and agent of the present invention can be used for improving the intestinal flora and increasing intestinal butyric acid production, and further, the physiological function brought about by the increase in intestinal butyric acid production. Can be used to exert

  Therefore, according to the present invention, a composition for improving intestinal flora and an agent for improving intestinal flora, comprising D-psicose as an active ingredient, and D-psicose as an active ingredient, Provided are a composition for promoting butyric acid production in the body and a promoter for butyric acid production in the intestine. The present invention also provides a composition comprising D-psicose as an active ingredient for exerting a physiological function resulting from increased intestinal butyric acid production, for example, promotion of blood glucose and / or lipid metabolism. A composition for enhancing immunity by normalizing intestinal mucosa, or promoting digestion and / or absorption by improving intestinal function, a promoter for blood glucose and / or lipid metabolism, an immunity improving agent for normalizing intestinal mucosa, and A digestion and / or absorption promoter for improving intestinal function is provided.

  According to the present invention, a composition for treating, preventing or ameliorating a disease or symptom, which comprises D-psicose as an active ingredient and can be treated, prevented or ameliorated by promoting the growth of Coprococcus spp. In the intestinal flora. And a therapeutic, prophylactic or ameliorating agent for the disease or condition is provided. Diseases and conditions that can be treated, prevented or ameliorated by promoting the growth of Coprococcus in the intestinal flora include inflammatory diseases (eg, inflammatory bowel diseases such as ulcerative colitis and Crohn's disease), malignant tumors ( For example, malignant tumors occurring in the intestinal tract such as colorectal cancer).

  The compositions and agents of the present invention are also at risk of developing a disease or condition that can be treated, prevented or ameliorated by promoting the growth of Coprococcus in the intestinal flora, or at risk of worsening intestinal flora. It can be ingested by the subject, thereby reducing the risk of developing the disease or the risk of worsening intestinal flora. That is, according to another aspect of the present invention, comprising D-psicose as an active ingredient, the risk of developing a disease or condition that can be treated, prevented or ameliorated by promoting the growth of Coprococcus spp. And / or a composition for reducing the risk of worsening intestinal flora, and the risk of developing a disease or condition that can be treated, prevented or ameliorated by promoting the growth of coprococcus in the intestinal flora and / or the intestinal flora Agents for reducing the risk of deterioration are provided. Here, "deterioration of intestinal flora" is caused not only by external factors such as medication, illness, diet, stress, lack of sleep, but also by physiological and genetic internal factors. In addition, "deterioration of intestinal flora" is used to include "disbiosis", and (1) the diversity of microbiota is lost, (2) the number of intestinal bacteria is reduced, and / or ( 3) Characterized by events such as pathogenic microorganisms becoming dominant. Further, "a subject at risk of developing a disease or symptom" means a subject who has no subjective symptom of the disease or symptom, but is at risk of developing the disease or symptom in the future. A “subject having” means a subject who has no subjective symptoms associated with deterioration of intestinal flora, but is at risk of deterioration of intestinal flora in the future. Further, "reduction of risk of onset" means that the probability of developing a disease or condition is reduced, and "reduction of risk of deterioration of intestinal flora" means that the probability of deterioration of intestinal flora is decreased. Means

  The composition and agent of the present invention contain D-psicose as an active ingredient. Although D-psicose has almost no calories, its sweetness is about 70% of that of sugar. Therefore, the composition and the agent of the present invention can suppress ingestion of calories as an alternative sweetener while coprococcus which is a useful enteric bacterium. It is advantageous in that the occupancy rate (%) of the genus bacteria in the human intestinal flora can be increased.

  The composition and agent of the present invention can be provided in the form of a drug (for example, pharmaceutical composition), quasi drug, food (for example, food composition), feed (for example, pet food), and the like, It can be carried out as described below.

  The active ingredient of the present invention, D-psicose, can be orally administered to humans and non-human animals. Examples of oral agents include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, and suspensions. These preparations can be prepared using a pharmaceutically acceptable carrier according to a method commonly used in the art. Pharmaceutically acceptable carriers include excipients, binders, diluents, additives, fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, etc. Is mentioned.

  When D-psicose, which is an active ingredient of the present invention, is provided as a food, D-psicose can be contained in the food as it is, and the food is a food containing an effective amount of D-psicose. Here, "containing an effective amount of D-psicose" refers to a content in which D-psicose is ingested within a range as described below when an amount that is normally consumed in an individual food is ingested. In addition, "food" means health food, functional food, food with health claims (for example, food for specified health use, food with nutritional function, food with functional claims), special-purpose food (for example, food for infants, food for pregnant women, disease). Foods for persons) and supplements are used in the meaning. The form of the “food” is not particularly limited, and may be, for example, a drink form, a semi-liquid or gel form, or a solid form.

The food provided in the present invention is not particularly limited as long as it is a food to which D-psicose can be added, and examples thereof are as follows.
Confectionery (for example, pudding, jelly, gummy candies, candies, drops, caramel, chewing gum, chocolate, pastries, butter cream, custard gremes, cream puffs, pancakes, bread, potato chips, french fries, popcorn, biscuits, crackers, Western confectionery such as pies, sponge cakes, castella, waffles, cakes, donuts, biscuits, and cookies; Japanese confectionery such as rice crackers, okaki, okoshi, manju, uiro, bean paste, yokan, water yokan, candy; frozen desserts such as sherbet)
・ Dried noodle products (eg macaroni, pasta, buckwheat, udon, ramen)
・ Egg products (eg mayonnaise, fresh cream)
-Beverages (for example, functional beverages, lactic acid beverages, lactic acid bacteria beverages, concentrated milk beverages, fruit juice beverages, fruit juice beverages, pulp beverages, vegetable juices, transparent carbonated beverages, carbonated beverages with fruit juice, fruit-colored carbonated beverages, alcoholic beverages, Beer style beverage)
・ Luxury items (eg green tea, black tea, instant coffee, cocoa, canned coffee drinks)
Dairy products (eg ice cream, yogurt, yogurt drinks, coffee milk, butter, butter sauce, cheese, fermented milk, processed milk)
・ Pastes (eg marmalade, jam, flower paste, peanut paste, fruit paste)
・ Retort foods (eg soup, stew, curry)
-Meat products (eg ham, sausage, bacon, dry sausage, beef jerky, lard)
・ Seafood products (eg fish ham, fish sausage, kamaboko, chikuwa, hampen, dried fish, bonito flakes, mackerel, dried sardines, sea urchin, salted squid, squid, dried mirin, dried shellfish, salmon etc. Goods)
・ Tsukudani (eg small fish, shellfish, wild vegetables, mushrooms, kelp)
・ Curries (eg instant curry, retort curry, canned curry)
・ Seasonings (for example, miso, powdered miso, soy sauce, powdered soy sauce, moromi, fish sauce, sauce, ketchup, oyster sauce, solid bouillon, roasted meat sauce, curry roux, stew base, soup base, soup base, paste , Instant soup, sprinkle, dressing, mayonnaise, vinegar, savory vinegar, powdered sushi vinegar, Chinese cabbage, tempura soup, noodle soup, salad oil, complex seasoning, mirin, fresh mirin, table sugar, sweetener for various seasonings such as coffee sugar As)
・ Fried products (eg fried food, fried food, instant noodles)
・ Other foods (eg soy milk, margarine, shortening, pickled fruit syrup)

  In producing the food provided by the present invention, D-psicose can be added to the raw material at an appropriate stage of the production process depending on the characteristics and purpose of each food.

  When the composition and the agent of the present invention are provided as a supplement, they can be produced according to a usual method for producing a supplement except that D-psicose is contained. Here, as the supplement, granules and powders produced by adding an excipient, a binder and the like to D-psicose or a sugar composition containing the same and granulating it, containing D-psicose or the same By adding an excipient, a thickener, etc. to the sugar composition and kneading the mixture, and adding D-psicose or the sugar composition containing the same, the excipient, the binder, etc., and kneading the mixture. Examples include the manufactured tablets, D-psicose or capsules in which a sugar composition containing the same is encapsulated. In the present invention, the subject himself or herself may add D-psicose having various properties (for example, liquid, solid, powder, granule, paste) to water, food and drink, eat, etc. You can also

  Since the drug and food of the present invention utilize D-psicose, which has a dietary experience as a rare sugar, a mammal (eg, human, mouse, rat, rabbit, dog, cat, cow, horse, It can be used safely for pigs, monkeys, etc.). The intake of D-psicose can be determined depending on the sex, age and weight of the recipient, symptoms, administration time, dosage form, administration route, drugs to be combined, and the like. When D-psicose is ingested as a food, the intake amount of D-psicose can be, for example, 1 to 50 g (preferably 2.5 to 30 g, more preferably 5 to 20 g) per day for an adult. Alternatively, it can be in the range of 0.016 g to 0.9 g, preferably 0.04 g to 0.5 g, and more preferably 0.07 g to 0.4 g per 1 kg of body weight of the intake subject. The number of times of ingestion is not particularly limited, and the above-mentioned effective dose may be ingested once a day or divided into several times. In addition, there is no particular limitation on the timing of ingestion, and it can be ingested at a time when the subject can easily ingest. In addition, the above-mentioned intake amount of D-psicose, the number of times of intake and the timing of intake, and the following intake modes of D-psicose are applicable when using D-psicose for both non-therapeutic purposes and therapeutic purposes. Ingestion can be read as administration if desired.

  The composition and agent of the present invention are not limited to use in combination with other orally ingestible compositions and agents. The composition and agent of the present invention can be used in combination with, for example, a material or composition that is expected to have an effect of improving the intestinal microflora, and thereby can further enhance the effect of promoting the growth of Coprococcus spp. Such materials and compositions include indigestible monosaccharides, sugar alcohols, oligosaccharides, dietary fiber and the like, and specific examples include mannose, tagatose, allose, xylitol, sorbitol, maltitol, erythritol. , Mannitol, fructooligosaccharide, galactooligosaccharide, soybean oligosaccharide, soybean oligosaccharide, dairy confectionery oligosaccharide, xylooligosaccharide, isomaltooligosaccharide, chitosan oligosaccharide, cellulose, chitin, chitosan, pectin, inulin, carrageenan, mannan, fucoidan, agarose, indigestible Examples thereof include dextrin, indigestible glucan, polydextrose, guar gum degradation product, resistant starch, silk protein, and resistant protein derived from cocoa beans, soybeans, rice, buckwheat, sake lees, and chemically modified products thereof.

  The composition and agent of the present invention can be provided as a composition comprising a daily intake amount of D-psicose effective for promoting the growth of Coprococcus spp. In this case, the composition and agent of the present invention may be packaged so that an effective intake amount for one day can be ingested, and as long as the effective intake amount for one day can be ingested, the packaging form is one package. There may be multiple packages. When it is provided in a packaged form, it is desirable that the description regarding the intake amount be provided on the package so that the effective intake amount for one day can be ingested, or the document in which the description is made is provided together. Further, when providing the effective intake amount for one day in a plurality of packages, it is possible to provide a plurality of packages of the effective intake amount for one day as a set for convenience of intake.

  The packaging form for providing the composition and the agent of the present invention is not particularly limited as long as it is a form that defines a certain amount, and examples thereof include wrapping paper, bags, soft bags, paper containers, cans, bottles and capsules. Examples thereof include containers that can be stored.

  The composition and agent of the present invention can be continuously ingested for at least 1 week or more, in order to exert their effects better, preferably for 2 weeks or more, more preferably for 1 month or more. is there. Here, “continuously” means to continue administration every day or at least once every two days. When the composition and agent of the present invention are provided in a packaged form, an effective intake amount for a certain period (for example, one week) may be provided as a set for continuous intake.

The food of the present invention may be labeled with a function of promoting the growth of Coprococcus spp in the intestinal flora and a function of improving the intestinal flora. In this case, the food of the present invention may be provided with some or all of the following indications in order to make the indications easy to understand by the consumer.
・ Preparing the intestinal environment ・ Improving the intestinal environment ・ Useful for improving the intestinal environment ・ Maintaining the favorable intestinal environment ・ Enhancing the intestinal flora ・ Preparing the intestines ・ Preparing the belly

  According to another aspect of the invention, Enterobacteriaceae comprising ingesting or administering to a subject (eg, a human or non-human animal) in need thereof an effective amount of D-psicose. Provided is a method for promoting the growth of Coprococcus spp. In the flora. The method for promoting the growth of Coprococcus spp. In the intestinal flora of the present invention can be carried out according to the description regarding the composition and agent of the present invention.

  According to yet another aspect of the invention, an enteral composition comprising ingesting or administering to a subject (eg, a human or non-human animal) in need thereof an effective amount of D-psicose. Treatment, prevention or amelioration method for diseases or conditions that can be treated, prevented or ameliorated by promoting the growth of Coprococcus spp in the flora, and diseases that can be treated, prevented or ameliorated by promotion of the growth of Coprococcus spp in the intestinal flora Alternatively, a method for reducing the risk of developing symptoms and / or the risk of worsening intestinal flora is provided. The treatment, prevention or amelioration method of the present invention and the risk reduction method of the present invention can be carried out according to the description regarding the composition and agent of the present invention.

  According to still another aspect of the present invention, the use of D-psicose for the production of a growth promoter for Coprococcus spp in the intestinal flora, and a growth promoter for Coprococcus spp in the intestinal flora The use of D-psicose as is provided. According to the present invention, the use of D-psicose for producing a therapeutic agent for a disease or condition which can be treated, prevented or ameliorated by promoting the growth of Coprococcus spp. Also provided is the use of D-psicose as a therapeutic agent, preventive agent or ameliorating agent for a disease or condition that can be treated, prevented or ameliorated by promoting the growth of Coprococcus spp in the intestinal flora. According to the present invention, further, for the production of an agent for reducing the risk of developing a disease or condition that can be treated, prevented or ameliorated by promoting the growth of Coprococcus in the intestinal flora and / or the risk of worsening the intestinal flora. Use of D-psicose as an agent for reducing the risk of developing a disease or symptom which can be treated, prevented or ameliorated by promoting the growth of coprococcus in the intestinal flora and / or a reduction in the risk of worsening intestinal flora Of D-psicose is provided. The use according to the invention can be carried out as described for the compositions and agents according to the invention.

  According to still another aspect of the present invention, D-psicose for use in promoting the growth of coprococcus in the intestinal flora, and treatment, prevention or treatment by promoting the growth of coprococcus in the intestinal flora D-psicose is provided for use in the treatment, prevention or amelioration of ameliorated diseases or conditions. According to the invention, D for use in reducing the risk of developing a disease or condition that can be treated, prevented or ameliorated by promoting the growth of Coprococcus in the intestinal flora and / or the risk of worsening the intestinal flora. -Pussy courses are provided. The above D-psicose can be carried out as described for the compositions and agents of the present invention.

  The methods and uses of the invention may be for use in mammals, including humans, and is intended for both therapeutic and non-therapeutic uses. In the present specification, “non-therapeutic” means not including an act of operating, treating or diagnosing a human (that is, a medical act for a human), specifically, a doctor or a doctor's instruction. It means that the person does not include a method of performing surgery, treatment or diagnosis on a human.

  The present invention will be described more specifically based on the following examples, but the present invention is not limited to these examples.

Example 1: Effect of D-psicose on intestinal flora (1) Selection of subjects Untreated persons who were 20 years or older and younger than 65 years old and who had slightly high levels of lipid and blood glucose levels were selected. Specifically, we selected those who correspond to the following a or b.
Those who have an LDL cholesterol level of 120 mg / dL or more and less than 160 mg / dL a Fasting blood glucose level of 110 mg / dL or more and less than 126 mg / dL or HbA1c (NGSP) of 6.2% or more and less than 6.5% People in the area

  The following screening was carried out for the persons corresponding to a or b, and the subjects were selected. Exclusion criteria for screening include (a) those with a history of severe history, (b) those with history of gastrointestinal resection surgery (excluding cecum resection), (c) blood glucose and lipid related drug treatment. Those who are allergic to (d) oligosaccharides and sweeteners, (e) who are continuously ingesting foods that claim to be effective in terms of blood sugar levels and lipids, (f) clinical tests and monitors other than this study Those who were participating in (food, pharmaceuticals, cosmetics or ointments) or planned to participate from the middle of this test period and (g) others were judged to be unsuitable as the subject by the investigator. Through screening, 7 subjects satisfying the above-mentioned a and 7 subjects satisfying the above-mentioned a (14 in total) were selected. Those who satisfied both a and a were classified as subjects who satisfied a. After giving a thorough explanation of the contents of the experiment to the subjects based on the guidelines issued by the Declaration of Helsinki, consent was obtained from all the subjects.

(2) Test food For 14 test subjects selected in the above (1), 15 g of D-psicose (manufactured by Matsutani Chemical Industry Co., Ltd., D-psicose content 99%) 15 g was added to drinking water etc. once a day as a test food. A single-group open test (open-label test) in which it was dissolved and ingested was performed. The feeding period of the test meal was one month.

(3) Metagenomic analysis of intestinal flora Before and after ingestion of D-psicose, stools were collected 1 month after ingestion and 1 month after the start of ingestion (hereinafter sometimes simply referred to as "1 month after ingestion"). Each intestinal flora DNA after a month was prepared. Using the intestinal flora DNA as a sample, metagenomic analysis by the 16S rRNA sequencing method was performed using MiSeq (manufactured by Illumina) to obtain the structure of the intestinal flora. The effect of ingestion of D-psicose on the intestinal flora was evaluated by comparing the microflora structure before and after one month of ingestion of D-psicose at the genus level.

(4) Statistical analysis Corresponding t-test was performed on the results of metagenomic analysis before and after ingestion of D-psicose obtained in (3) above. The risk rate [P value] was set to less than 5%.

(5) Results The results are shown in Table 1. Among the detected 229 OTUs (Operational Taxonomic Units, which are units for handling as one unit in data operation and are also called “operational classification units”), the top 30 with high occupancy in the intestinal flora The bacterial groups were evaluated, and the OTUs at positions 31 to 229 were collectively set as “others”. In addition, the unclassifiable OTU2 bacterial groups were designated as "unclassifiable OTU1" and "unclassifiable OTU2".

From the results of Table 1, the occupancy of the genus Coprococcus was significantly increased in the intestinal flora one month after the ingestion, as compared with that before ingestion of D-psicose. Specifically, the average occupancy of Coprococcus in the intestinal flora was significantly increased from 4.19% to 6.36% (P = 0.028). Since the genus Coprococcus is a bacterium that produces butyric acid, it is known that the increase of butyric acid production in the intestine suppresses cancer cells, normalizes the intestinal mucosa, regulates intestinal function, etc. It was confirmed to show an effect of improving the flora. Further, Bifidobacterium is the most dominant species in the intestinal flora (Bifidobacterium) genus and Burautia (Blautia) genus, an increase of respectively the average occupancy rate was observed was significant difference is confirmed.

Claims (8)

  A composition for promoting the growth of Coprococcus spp in the intestinal flora, which comprises D-psicose as an active ingredient.   A composition according to claim 1 for ingestion.   The composition according to claim 1 or 2, which comprises an effective daily intake of D-psicose in humans.   The composition according to any one of claims 1 to 3, wherein the effective daily intake of D-psicose in a human is 1 to 50 g.   The composition according to any one of claims 1 to 4, which is ingested continuously for 1 week or more.   The composition according to any one of claims 1 to 5, which is in a unit packaging form.   The composition according to any one of claims 1 to 6, which is a food composition. The composition according to any one of claims 1 to 7, which is used for treating, preventing or ameliorating a disease or condition that can be treated, prevented or ameliorated by promoting the growth of Coprococcus in the intestinal flora.