WO2020031957A1 - 腸内環境改善用組成物及び腸内細菌叢改善方法 - Google Patents
腸内環境改善用組成物及び腸内細菌叢改善方法 Download PDFInfo
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- WO2020031957A1 WO2020031957A1 PCT/JP2019/030724 JP2019030724W WO2020031957A1 WO 2020031957 A1 WO2020031957 A1 WO 2020031957A1 JP 2019030724 W JP2019030724 W JP 2019030724W WO 2020031957 A1 WO2020031957 A1 WO 2020031957A1
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
- A23V2200/3202—Prebiotics, ingredients fermented in the gastrointestinal tract by beneficial microflora
Definitions
- the present invention relates to a composition for improving intestinal flora.
- the present invention also relates to a method for improving intestinal flora.
- the invention further relates to isoxanthohumol and / or the use of xanthohumol for improving intestinal flora.
- the intestinal flora (intestinal flora) not only functions as a barrier to prevent the invasion of foreign pathogens, but also affects the host's energy regulation, nutrition intake, immune function, etc.
- the intestinal flora is composed of obesity and diabetes , It is reported to fluctuate in relation to aging and the like. For example, constipation, diarrhea, inflammatory bowel disease, cancer, allergy, asthma and the like have been reported as conditions or diseases related to the intestinal flora.
- diet is a factor that affects the intestinal flora, and as a method of controlling the intestinal flora with the expectation of some health benefits, it works well for the host (particularly human) body, Probiotics that ingest the contributing microorganisms (good bacteria) and prebiotics for the purpose of multiplying the good bacteria are included.
- good bacteria such as bifidobacteria, lactic acid bacteria, and bacteria of the genus Ackermansia described below.
- Non-Patent Document 1 In addition, in the intestinal flora of obese persons, the proportion of Firmicutes phylum bacteria increased and the proportion of Bacteroidetes phylum classified as opportunistic bacteria decreased, so that Firmicutes phylum / Bacteroidetes was reduced. It is reported that it is important to control the ratio of the gates (Non-Patent Document 1).
- Ackermansia genus bacteria such as Ackermansia muciniphila (scientific name: Akermansia muciniphila) are intestinal bacteria present in the human intestinal mucus layer, and are abundant in non-obese humans, but in obese humans It is known that only small amounts are present. It has been reported that obesity model mice and type 2 diabetes model mice also contain fewer Ackermansia bacteria than normal mice (Non-Patent Document 2).
- the intestinal epithelial cells have a host defense function associated with stress and obesity, ie, the breakdown of the intestinal barrier function, and the accompanying influx of pathogenic bacteria and endotoxin lipopolysaccharide (LPS) have caused chronic inflammation and systemic inflammation. It has been reported to be associated with the onset of the disease. It has been reported that ingestion of bacteria of the genus Ackermannia enhances the intestinal barrier function and reduces lipopolysaccharide (LPS) flowing into serum (Non-Patent Document 2). Therefore, enhancement of the intestinal barrier function can be expected by growing Ackermansia bacteria in the intestine. By enhancing the intestinal barrier function, suppression of the development of chronic inflammation can be expected.
- Propagating Ackermansia genus bacteria, which are good bacteria, in the intestine is considered to be beneficial in maintaining and promoting the health of the host, and one of the improved intestinal flora and intestinal environment It can be said that it is a state.
- Non-Patent Document 3 shows the effect of promoting the growth of Ackermansia bacteria by ingestion of the antidiabetic drug metformin.
- metformin which is a pharmaceutical, has side effects such as lactic acidosis. Therefore, there is a need for a substance suitable for use in improving the intestinal flora and intestinal environment in a daily diet.
- Patent Literature 1 discloses an Ackermansia bacterium bacterial growth promoter containing as an active ingredient proanthocyanidins of pentamer or more derived from plants.
- an anti-obesity effect is exhibited in both a proanthocyanidin (PP) of pentamer or more and a low-molecular procyanidin fraction (OP) of monomer to tetramer having a lower degree of polymerization.
- PP proanthocyanidin
- OP low-molecular procyanidin fraction
- Non-Patent Document 4 reports an anti-inflammatory effect in the intestine by spent hops (hop extract lees) containing polyphenols. However, the effect of spent hops on the intestinal flora is unknown, and the active ingredient is not specified.
- isoxanthohumol and xanthohumol which are a kind of hop-derived polyphenol, have an effect of promoting the growth of bacteria of the genus Akermansia. And found to exhibit an intestinal flora improving effect. Isoxanthohumol and xanthohumol also had an intestinal flora-improving effect in reducing the ratio of Firmicutes / Bacteroidetes bacteria in obese humans.
- the present invention finds that Ackermansia genus bacterial growth activity, the activity of reducing the ratio of Firmicutes bacteria / Bacteroidetes phylum, the effect of improving the intestinal flora based on the activity, The intestinal barrier function enhancing effect and the intestinal environment improving effect have not been reported so far.
- the present invention relates to, but is not limited to, the following composition for improving the intestinal flora, a method for improving the intestinal flora, and the like.
- a composition for improving intestinal bacterial flora comprising isoxanthohumol and / or xanthohumol as an active ingredient.
- the composition for improving intestinal flora according to [2] wherein the good bacteria are bacteria belonging to the genus Akermansia.
- [4] The improvement of the intestinal flora according to the above [1], wherein the improvement of the intestinal flora is a decrease in the abundance ratio of the Firmicutes bacterium to the Bacteroidetes bacterium (Firmicutes / Bacteroidetes).
- Composition [5] The composition for improving intestinal microflora according to any one of the above [1] to [4], which is used for enhancing intestinal barrier function.
- [7] The composition for improving intestinal bacterial flora according to any one of the above [1] to [6], which is a beverage.
- the novel composition for intestinal flora improvement which can increase the abundance ratio of the good bacteria in intestinal flora can be provided.
- the intestinal flora improving composition of the present invention is ingested, for example, in the intestinal flora, the abundance ratio of Ackermansia bacteria, which are good bacteria, can be increased.
- Such an action to increase the ratio of good bacteria can improve intestinal flora, improve intestinal environment, enhance intestinal barrier function, and the like.
- FIG. 1 is a graph showing the ratio of bacteria constituting the intestinal flora in each group.
- the composition for improving intestinal flora of the present invention contains isoxanthohumol and / or xanthohumol as an active ingredient.
- the composition for improving intestinal microflora may contain either one of isoxanthohumol and xanthohumol as an active ingredient, or may contain both of them as active ingredients.
- the composition for improving intestinal microflora preferably contains isoxanthohumol, or isoxanthohumol and xanthohumol as active ingredients.
- Isoxanthohumol can be prepared, for example, from a hop (Humulus @ lupulus) extract, which is a plant of the hemp family, via a process such as heating. By heating the hop extract, isoxanthohumol can be generated in the extract.
- the hop extract is usually prepared by extracting hop cones with a solvent and, if necessary, through a process relating to purification, and can be obtained by a known hop extract preparation method. Examples of the extraction method include an extraction method using an ethanol solvent used as a method for preparing a hop extract used for beer brewing. Hop extracts are commercially available, and commercially available hop extracts can also be used.
- the hop extract is preferably heated at 80 to 140 ° C.
- isoxanthohumol (more preferably 85 to 100 ° C.) for 15 minutes to 5 hours (more preferably 20 minutes to 3 hours) to produce isoxanthohumol.
- Purification of the hop extract for preparing isoxanthohumol is performed by a known method. Examples of the purification method include methods such as use of an HPLC or an adsorption column, and precipitation using a change in solubility.
- Isoxanthohumol can also be produced by heating xanthohumol to isomerize it. The heating temperature at this time is preferably 80 to 140 ° C. (more preferably 85 to 100 ° C.) for 15 minutes to 5 hours (more preferably 20 minutes to 3 hours).
- the isoxanthohumol obtained by the isomerization treatment can be concentrated or purified by a known method (for example, filtration, concentration under reduced pressure, lyophilization and the like) as necessary.
- Xanthohumol is a component derived from hops, and is obtained by extracting hops with a solvent. For example, pellets obtained by crushing dried hops are immersed and extracted in an organic solvent such as alcohol. Next, the obtained extract can be obtained by concentrating or drying, and then separating or purifying it using chromatography or the like.
- the temperature at the time of extraction, fractionation, and purification from hops is preferably less than 80 ° C, for example, more preferably 5 to 70 ° C.
- isoxanthohumol and xanthohumol commercially available products can also be used.
- isoxanthohumol and / or a plant-derived raw material rich in xanthohumol may be contained in the composition of the present invention as long as the effects of the present invention are exerted.
- Isoxanthohumol and xanthohumol are compounds contained in natural products and foods and drinks, and have experienced eating. For this reason, from the viewpoint of safety, it is considered that isoxanthohumol and / or xanthohumol have few problems even when taken daily, for example. Therefore, according to the present invention, it is possible to provide a composition for improving intestinal bacterial flora containing a highly safe component as an active ingredient. It has also been reported that isoxanthohumol is stable even at a high temperature condition of, for example, 100 ° C.
- sterilization conditions are defined as standard standards for soft drinks, etc., for example, those with a pH of 4.0 or more (excluding those with a pH of 4.6 or more and a water activity exceeding 0.94) Requires heating at 85 ° C. for 30 minutes.
- isoxanthohumol is considered to have a high beverage suitability.
- Isoxanthohumol and / or xanthohumol contained in the composition for improving intestinal microflora can be quantified by, for example, high performance liquid chromatography (HPLC) or LC-MS / MS.
- Isoxanthohumol and xanthohumol also have the advantage that they can be easily analyzed quantitatively and are easy to use as active ingredients such as functionally labeled foods that require quantitative analysis and standardization of active ingredients.
- the intestinal flora refers to a bacterial population (microflora) present in the intestine.
- Bacteria that make up the intestinal flora include those that play a positive role in the body of the host (especially humans), those that contribute to health (good bacteria), those that have a bad effect on the body by producing harmful substances, Some bacteria work badly in the intestine when their resistance is weakened, while others do no harm. Good bacteria can also be called useful bacteria.
- the abundance ratio of each bacterial species in the intestinal flora is sometimes called balance.
- the proportion (balance) of bacteria constituting the intestinal flora varies depending on factors such as eating habits, age, stress, and taking of drugs such as antibiotics.
- the balance of the gut flora affects the health of the host.
- improvement of the intestinal flora means that the intestinal flora changes in a direction that is beneficial to the host (particularly, human). Intestinal flora improvement involves improving the balance of the gut flora.
- the improvement of the intestinal microflora is preferably an increase in the abundance ratio (existence ratio) of good bacteria in the intestinal microflora.
- the ratio of good bacteria in the intestinal flora is the occupancy of the good bacteria in the total bacterial count of the intestinal flora.
- An increase in the ratio of good bacteria in the intestinal flora usually improves indicators such as metabolites produced by the intestinal flora, intestinal pH, etc. in a direction beneficial to the host.
- the intestinal flora is improved by increasing the abundance ratio of good bacteria, or metabolites produced by the intestinal flora, indices such as intestinal pH, are more likely to be beneficial to the host.
- the composition for improving intestinal flora of the present invention can be used as a composition for improving intestinal environment.
- the abundance ratio of good bacteria in the intestinal flora can be determined, for example, by performing 16S rRNA gene analysis of bacteria in feces.
- Ackermansia bacteria examples include Ackermansia bacteria, Bifidobacteria, and lactic acid bacteria, and Ackermansia bacteria are preferred.
- the intestinal barrier function refers to a function of preventing invasion (permeation) of foreign substances (for example, toxins such as endotoxins, inflammatory substances, undigested substances, etc.) from outside the intestinal epithelial cells (in the intestinal tract) to the body.
- foreign substances for example, toxins such as endotoxins, inflammatory substances, undigested substances, etc.
- a state in which invasion of foreign substances into the body from outside the intestinal epithelial cells is promoted as compared to a normal state is referred to as a state in which the permeability of the intestinal epithelial cells to foreign substances is increased.
- the enhancement of the intestinal barrier function means both suppressing the increase in permeability of foreign substances in intestinal epithelial cells and reducing the permeability of foreign substances in intestinal epithelial cells.
- the intestinal barrier function enhancing effect is shown, for example, by increasing the electrical resistance value (transepithelial electrical resistance (TEER)) of intestinal epithelial cells or by suppressing the decrease in TEER.
- TEER transepithelial electrical resistance
- Non-Patent Document 1 a decrease in the abundance ratio of the Firmicutes bacteria to the Bacteroidetes bacteria (Firmicutes / Bacteroidetes) is an aspect of improving the intestinal flora and can be an index of improving the intestinal environment.
- the decrease in the phylums of Firmicutes / Bacteroidetes can be translated into an increase in the abundance ratio of Bacteroides (Bacteroidetes) to Bacteroides (Bacteroidetes) / Bacteroides (Bacteroides).
- isoxanthohumol and xanthohumol have the effect of increasing the abundance of Ackermansia bacteria in the intestinal flora and improving the intestinal flora.
- mice that were orally ingested isoxanthohumol or xanthohumol the abundance ratio of Firmicutes phylum to Bacteroidetes bacterium (Firmicutes / Bacteroidetes) decreased. Therefore, isoxanthohumol and isoxanthohumol have an effect of reducing the abundance ratio of Firmicutes bacteria to Bacteroidetes bacteria (Firmcutes / Bacteroidetes).
- the composition for improving the intestinal flora of the present invention contains isoxanthohumol and / or xanthohumol as an active ingredient, so that the presence of good bacteria such as bacteria of the genus Akermansia in the intestinal flora. Can be used to increase the ratio. Increasing the abundance of Ackermansia bacteria is effective in enhancing the intestinal barrier function. Therefore, the composition for improving intestinal bacterial flora of the present invention can be suitably used for enhancing intestinal barrier function. By enhancing the intestinal barrier function, effects such as prevention or amelioration of chronic inflammation, prevention or amelioration of constipation, prevention or amelioration of diarrhea, reduction of stomach discomfort, and improvement of constitution can be expected.
- the composition for improving intestinal flora of the present invention can be used for reducing the abundance ratio of Firmicutes bacteria to Bacteroidetes bacteria (Firmicutes / Bacteroidetes).
- the composition for improving the intestinal flora of the present invention for example, by increasing the ratio of good bacteria in the intestinal flora, to improve the intestinal flora, to improve the intestinal environment, or It can be used to enhance intestinal barrier function.
- the composition for improving the intestinal flora of the present invention is also intended to improve the intestinal flora by reducing the ratio of the gates of Firmicutes / Bacteroidetes in the intestinal flora, thereby improving the intestinal environment. Can be used.
- the composition for improving the intestinal flora of the present invention is characterized by increasing the abundance of good bacteria, particularly Ackermansia sp., In the intestinal flora, thereby preventing or improving the effective condition or disease.
- Such conditions or diseases include, for example, those that can be expected to be prevented or improved by enhancing intestinal barrier function.
- conditions or diseases that can be prevented or improved by enhancing the intestinal barrier function include chronic inflammation, constipation, diarrhea, irritable bowel syndrome, infectious diseases, food allergies, and the like.
- prevention of a condition or disease includes preventing the onset of the condition or disease, delaying the onset of the condition or disease, reducing the incidence of the condition or disease, reducing the risk of developing the condition or disease. It refers to reducing. Improvement of a condition or disease refers to relieving the subject from the condition or disease, reducing the symptoms of the condition or disease, delaying or preventing the progress of the condition or disease, and the like.
- the composition for improving intestinal flora of the present invention can be applied to either therapeutic use (medical use) or non-therapeutic use (non-medical use).
- the composition for improving intestinal bacterial flora of the present invention can be in the form of food and drink, medicine, quasi-drugs, feed and the like.
- the composition for improving the intestinal flora of the present invention may itself be a food and drink for improving the intestinal flora, a medicine, a quasi-drug, a feed, etc. Materials or preparations.
- the composition for improving the intestinal flora of the present invention can be provided, for example, in the form of an agent, but is not limited to this form.
- the agent can be provided as it is as a composition or as a composition containing the agent.
- the composition for improving intestinal flora of the present invention can also be referred to as an intestinal flora improving agent.
- the composition for improving intestinal bacterial flora of the present invention is preferably an oral composition.
- the oral composition include foods and drinks, oral medicines, quasi-drugs, and feeds, and are preferably foods and drinks or oral medicines, and more preferably foods and drinks.
- the composition for improving the intestinal microflora of the present invention can contain any additive and any component in addition to isoxanthohumol and / or xanthohumol as long as the effects of the present invention are not impaired. .
- These additives and components can be selected according to the form of the composition and the like, and those generally usable for foods and drinks, medicines, quasi-drugs, feeds, and the like can be used.
- the production method is not particularly limited, and it can be produced by a general method.
- a composition for improving intestinal microflora containing isoxanthohumol can also be produced by blending a hop extract and performing a step of heating the hop extract in the production thereof.
- isoxanthohumol and / or xanthohumol may be added to a component usable for food or drink (for example, a food material, used as needed).
- a component usable for food or drink for example, a food material, used as needed.
- Various foods and beverages can be obtained by blending such food additives.
- Foods and drinks are not particularly limited, and include, for example, general foods and drinks, health foods, health drinks, functionally labeled foods, foods for specified health use, foods and drinks for the sick, and the like.
- a preferred example of the composition for improving the intestinal flora of the present invention is a beverage.
- a composition for improving intestinal microflora containing isoxanthohumol is more suitable for beverages.
- the beverage may be a non-alcoholic beverage or an alcoholic beverage.
- the non-alcoholic beverage include a tea-based beverage, a coffee beverage, a non-alcoholic beer taste beverage, a carbonated beverage, a functional beverage, a fruit / vegetable beverage, a dairy beverage, a soy milk beverage, and a flavored water.
- composition for improving intestinal microflora of the present invention is a beverage, a tea-based beverage, a coffee beverage, an alcoholic beverage, a non-alcoholic beer taste beverage, a carbonated beverage, a functional beverage, a fruit / vegetable beverage, a dairy beverage, It is preferably a soy milk drink or flavored water.
- the composition for improving intestinal microflora of the present invention is a tea-based beverage, it is preferably a black tea beverage or a sugar-free tea beverage.
- sugar-free tea beverage include a green tea beverage, an oolong tea beverage, a barley tea beverage, a brown rice tea beverage, a pigeon barley tea beverage, and a sugar-free black tea beverage.
- the composition for improving intestinal bacterial flora of the present invention is a coffee beverage, it is preferably packaged coffee or liquid coffee.
- alcoholic beverages examples include beer, beer-based beverages, beer and alcoholic beverages other than beer-based beverages.
- the composition for improving intestinal microflora of the present invention is a beer-based beverage, it is preferably a low-malt beer or a third beer.
- the composition for improving intestinal flora of the present invention is an alcoholic beverage other than beer and beer-based beverages, it is preferably shochu, chuhai, liqueur, cocktail, spirits, and whiskey.
- non-alcoholic beer-taste beverage in the present specification means a carbonated beverage having a beer-like flavor, which is usually a non-fermented non-alcoholic beverage, which does not substantially contain alcohol.
- the non-alcoholic beer taste beverage does not exclude a beverage containing an extremely small amount of alcohol that cannot be detected.
- composition for improving intestinal microflora of the present invention is a carbonated beverage
- it is preferably a cola flavor beverage, a transparent carbonated beverage, a ginger ale, a juice-based carbonated beverage, a milk-containing carbonated beverage, or a sugar-free carbonated beverage.
- composition for improving intestinal microflora of the present invention is a functional drink, it is preferably a sports drink, an energy drink, a health support drink or a pouch jelly drink.
- composition for improving intestinal microflora of the present invention is a fruit / vegetable beverage, it is preferably a 100% fruit beverage, a fruit-containing beverage, a low-juice-containing soft drink, a fruit-grain-containing fruit beverage, or a pulp beverage.
- composition for improving intestinal microflora of the present invention is a dairy beverage, it is preferably milk, a drink yogurt, a lactic acid bacterium beverage or a milk-containing soft drink.
- composition for improving intestinal bacterial flora of the present invention is a soymilk drink, it is preferably a soymilk or soybean drink.
- the form of the beverage is not particularly limited, and may be a packaged beverage.
- Containers for packaged beverages are not particularly limited, and containers of any form and material may be used.
- metal containers such as aluminum cans and steel cans; resin containers such as PET bottles; paper such as paper packs Containers; glass containers such as glass bottles; and commonly used containers such as wooden containers such as barrels can be used.
- composition for improving the intestinal microflora of the present invention is used as a drug or a quasi-drug
- a pharmacologically acceptable carrier if necessary, is added to isoxanthohumol and / or xanthohumol
- the pharmaceuticals or quasi-drugs of various dosage forms can be obtained by blending additives and the like.
- Such carriers, additives, and the like can be used in medicines or quasi-drugs, as long as they are pharmacologically acceptable, for example, excipients, binders, disintegrants, lubricants, One or more of an antioxidant, a coloring agent, and the like are included.
- Examples of the administration (ingestion) form of the medicament or quasi-drug include oral, enteral, transmucosal, and injection, and the oral administration form is preferable from the viewpoint of more sufficiently obtaining the effects of the present invention.
- the composition for improving intestinal microflora is used as a medicine, it is preferably used as an oral medicine.
- Examples of the dosage form of the preparation for oral administration include liquids, tablets, powders, fine granules, granules, dragees, capsules, suspensions, emulsions, chewables and the like.
- the medicament may be a non-human veterinary medicament.
- composition for improving intestinal microflora of the present invention when used as a feed, for example, isoxanthohumol and / or xanthohumol may be added to the feed.
- Feed also includes feed additives. Examples of the feed include feed for livestock used for cattle, pigs, chickens, sheep, horses, and the like; feed for small animals used for rabbits, rats, mice, and the like; and pet food used for dogs, cats, small birds, and the like.
- the content of isoxanthohumol and / or xanthohumol in the composition for improving intestinal bacterial flora of the present invention is not particularly limited, and can be set according to the form and the like.
- the content of isoxanthohumol and / or xanthohumol for example, the total content of isoxanthohumol and xanthohumol is preferably 0.0001% by weight or more in the composition for improving intestinal microflora, and 0.1% or more. 001% by weight or more is more preferable, and 90% by weight or less is preferable.
- the total content of isoxanthohumol and / or xanthohumol is preferably 0.0001 to 90% by weight in the composition for improving intestinal microflora. , 0.001 to 90% by weight.
- the total content of isoxanthohumol and xanthohumol is the content of isoxanthohumol or xanthohumol when the composition contains only one of these, and the composition is isoxanthohumol and xanthohumol. When tofumol is contained, it is the total content of these.
- the composition for improving intestinal microflora of the present invention when used as a food or drink, medicine, quasi-drug, feed, or the like, the total content of isoxanthohumol and xanthohumol may be in the above range. preferable.
- composition for improving intestinal bacterial flora of the present invention can be taken or administered by an appropriate method depending on its form. From the viewpoint of sufficiently obtaining the effects of the present invention, the composition for improving intestinal microflora of the present invention is preferably orally ingested (orally administered).
- the amount of the composition for improving the intestinal flora of the present invention is not particularly limited, and may be any amount (effective amount) capable of improving the intestinal flora. What is necessary is just to set suitably according to a form, an administration method, a subject's weight, etc.
- the ingestion of the composition for improving the intestinal microflora is determined as the total intake of isoxanthohumol and xanthohumol as a total body weight per day. 60 kg, preferably 1 to 200 mg, more preferably 5 to 60 mg.
- the composition for improving the intestinal microflora of the present invention is an oral composition for allowing an adult to ingest or administer the above-mentioned amount of isoxanthohumol and / or xanthohumol per 60 kg body weight per day. It may be a composition.
- the composition for improving intestinal microflora of the present invention is to be taken continuously.
- the composition for improving intestinal flora is preferably taken continuously for 2 weeks or more, and more preferably taken for 8 weeks or more.
- the subject to which the composition for improving the intestinal microflora of the present invention is to be ingested is not particularly limited. Preferably it is a human or non-human mammal, more preferably a human.
- the subject to be ingested the composition for improving the intestinal flora of the present invention is preferably a subject requiring or wishing to improve the intestinal flora, or a subject requiring or wishing to improve the intestinal environment.
- Such subjects include, for example, humans with irritable bowel syndrome, constipation, diarrhea, food allergies, and the like.
- the composition for improving intestinal flora of the present invention can also be used for healthy persons for the purpose of, for example, preventing a condition or disease in which prevention or improvement can be expected by improving intestinal flora.
- the composition for improving the intestinal flora of the present invention contains a highly safe component contained in natural products and foods and drinks as an active ingredient, and exhibits a high intestinal flora improving effect when continuously ingested. .
- the composition for improving the intestinal flora of the present invention is, for example, humans having the above-mentioned irritable bowel syndrome, constipation, diarrhea, food allergy, healthy subjects, etc. It increases the ratio of good bacteria in the flora, and is useful as a health food, a functional food, etc. for use in improving the intestinal flora and improving the intestinal environment.
- the composition for improving the intestinal flora of the present invention may be labeled with a function based on the intestinal flora improving action.
- the composition for improving the intestinal flora of the present invention includes, for example, “balance the intestinal bacteria”, “maintain an intestinal environment”, “help maintain intestinal health”, and “have an intestinal barrier function.” Display of one or more functions of “enhance”, “increase good bacteria”, “increase useful bacteria”, “condition stomach”, “reduce stomach discomfort” and “improve constitution” May be added.
- the composition for improving intestinal bacterial flora of the present invention is preferably a food or drink labeled with the above. Further, the above display may be a display indicating that it is used to obtain the above function.
- the present invention also includes the following method.
- the method may be a therapeutic or a non-therapeutic method.
- “Non-therapeutic" is a concept that does not include medical practice, i.e., human surgery, treatment or diagnosis.
- Ingestion of isoxanthohumol and / or xanthohumol can increase the ratio of good bacteria in the intestinal flora.
- Such an action makes it possible to improve the intestinal flora and the intestinal environment.
- the present invention also includes the following uses.
- the above uses are preferably for use in human or non-human mammals, more preferably humans.
- the use may be a therapeutic use or a non-therapeutic use.
- intestinal flora improvement, good bacteria and preferred embodiments thereof are the same as those of the above-described composition for improving intestinal flora of the present invention.
- the present invention provides a method for increasing the ratio of Ackermansia bacteria in the intestinal flora to which isoxanthohumol and / or xanthohumol is ingested or administered to a subject; isoxanthohumol and / or xanthohumol A method for reducing the abundance ratio of Firmicutes bacteria to Bacteroidetes phylum bacteria in the intestinal flora of ingesting or administering a maul to a subject (Firmicutes phylum / Bacteroidetes phylum); Ackermansia in intestinal flora ( Use of isoxanthohumol and / or xanthohumol to increase the abundance of bacteria of the genus Akermansia); Bacteroides
- isoxanthohumol and / or xanthohumol be continuously ingested or administered to the subject from the viewpoint of more sufficiently obtaining the effects of the present invention. From the viewpoint of obtaining the effects of the present invention more sufficiently, when ingesting or administering isoxanthohumol and / or xanthohumol to a subject continuously, it is preferable to continuously ingest or administer for 2 weeks or more, It is more preferable to continuously ingest or administer for 8 weeks or more.
- the subject is administered or ingested with isoxanthohumol and / or xanthohumol at least once a day, for example, once to several times a day (eg, two to three times). Good.
- the subject may be administered or ingested isoxanthohumol and / or xanthohumol in an amount (also referred to as an effective amount) capable of improving the intestinal microflora.
- the preferable intake amount and administration subject of isoxanthohumol and / or xanthohumol are the same as those of the composition for improving the intestinal bacterial flora of the present invention described above.
- Isoxanthohumol and / or xanthohumol may be administered or taken as it is, or may be administered or taken as a composition containing isoxanthohumol and / or xanthohumol.
- the composition for improving intestinal bacterial flora of the present invention described above may be administered or taken.
- isoxanthohumol and / or xanthohumol can be used for production of foods and drinks, medicines, quasi-drugs, feeds and the like used for improving intestinal microflora.
- the present invention also includes use of isoxanthohumol and / or xanthohumol for producing a composition for improving intestinal flora. All of the scientific and patent literature mentioned herein is incorporated herein by reference.
- ⁇ Preparation Example 1> Preparation of Xanthohumol and Isoxanthohumol Isoxanthohumol and xanthohumol were isolated and purified from a hop extract (manufactured by Asama Kasei Co., Ltd.) by the following method. That is, isoxanthohumol and xanthohumol are purified from the hop extract by normal phase column chromatography, reverse phase column chromatography, and preparative HPLC purification, and the purity is determined to be 95% or more by HPLC analysis. confirmed.
- Example 1 Examination of intestinal flora improving effect by ingestion of xanthohumol and isoxanthohumol Using a high-fat diet-ingested model mouse, the effects of xanthohumol and isoxanthohumol on the intestinal flora were determined by the following procedure. investigated.
- Table 1 shows the group composition (group name, basal feed, test substance, and dose of the test substance) in this test.
- the dose is the intake (mg) of the test substance per kg of body weight per day.
- the normal diet is "control feed” (D12450J)
- the 60-kcal% high fat diet is “ultra high fat feed” (D12492) (above, manufactured by Research Diets)
- the catechins are "polyphenone 70A" as a preparation. (Product name, manufactured by Mitsui Norin Co., Ltd.). Catechins were used as a positive control.
- Xanthohumol and isoxanthohumol used were the samples (purity 95% or more) obtained in Preparation Example 1.
- mice C57BL / 6J, male, 7 weeks old, CLEA Japan, Inc.
- quarantine and acclimatizing for 1 week, animals were selected based on changes in body weight from animals with no abnormalities observed in general condition observation did.
- the test substance was orally ingested once a day for 8 weeks. At the time of ingestion of the test substance, an administration liquid obtained by mixing the test substance and a solvent was used. A 0.5% by weight aqueous solution of sodium carboxymethylcellulose (CMC) was used as the solvent. In the administration of the test substance, the amount of the liquid to be taken by the mouse was 10 mL / kg, and the amount of the test substance and the amount of the liquid were calculated based on the latest body weight.
- CMC sodium carboxymethylcellulose
- the feces fresh stool collected 8 weeks after the start of the test substance ingestion were analyzed, and 16S rRNA gene analysis was performed.
- the 16S rRNA gene analysis was performed by the method described in Examples of JP-A-2018-8911. From this gene analysis, the abundance ratio (existence ratio) of the intestinal bacteria contained in the feces was determined and defined as the abundance ratio of the bacteria constituting the intestinal flora.
- FIG. 1 shows the abundance ratio (group average) of bacteria constituting the intestinal flora in each group.
- the abundance ratio shown in FIG. 1 is the ratio (occupancy) of each bacterium to the total number of bacteria contained in feces.
- Verrucomicrobia (Bercomicobium) in FIG. 1 is a higher class to which Ackermansia bacteria belong, and this analysis shows only Ackermansia bacteria.
- the dose (mg / kg) of isoxanthohumol (IXN) and xanthohumol (XN) in FIG. 1 is the intake amount (mg) of the test substance per kg of body weight per day.
- the ratio of the presence of Firmicutes bacteria / Bacteroidetes bacteria was 4.2 in the normal diet group, 7.4 in the high fat diet group, 1.7 in the catechin group, and 3. in the xanthohumol (60 mg / kg) group. 2. It was 6.0 in the isoxanthohumol (60 mg / kg) group (group No. 5) and 2.4 in the isoxanthohumol (180 mg / kg) group (group No. 6).
- FIG. 1 shows the results of ingestion of each test substance for 8 weeks.
- the cecal contents were 2 weeks after the start of the test substance ingestion.
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Abstract
Description
〔1〕イソキサントフモール及び/又はキサントフモールを有効成分として含む腸内細菌叢改善用組成物。
〔2〕上記腸内細菌叢改善が、腸内細菌叢における善玉菌の存在比率の増加である上記〔1〕に記載の腸内細菌叢改善用組成物。
〔3〕上記善玉菌が、アッカーマンシア(Akkermansia)属細菌である上記〔2〕に記載の腸内細菌叢改善用組成物。
〔4〕上記腸内細菌叢改善が、バクテロイデス(Bacteroidetes)門細菌に対するフィルミクテス(Firmicutes)門細菌の存在比率(Firmicutes門/Bacteroidetes門)の減少である上記〔1〕に記載の腸内細菌叢改善用組成物。
〔5〕腸管バリア機能増強のために使用される上記〔1〕~〔4〕のいずれかに記載の腸内細菌叢改善用組成物。
〔6〕飲食品である上記〔1〕~〔5〕のいずれかに記載の腸内細菌叢改善用組成物。
〔7〕飲料である上記〔1〕~〔6〕のいずれかに記載の腸内細菌叢改善用組成物。
〔8〕上記飲料が、茶系飲料、コーヒー飲料、アルコール飲料、ノンアルコールビールテイスト飲料、炭酸飲料、機能性飲料、果実・野菜系飲料、乳性飲料、豆乳飲料又はフレーバーウォーターである上記〔7〕に記載の腸内細菌叢改善用組成物。
〔9〕「腸内細菌のバランスを整える」、「腸内環境を良好に保つ」、「腸の健康維持に役立つ」、「腸管バリア機能を高める」、「善玉菌を増やす」、「有用菌を増やす」、「おなかの調子を整える」、「おなかの不快感を軽減する」及び「体質を改善する」の1又は2以上の機能の表示を付した上記〔1〕~〔8〕のいずれかに記載の腸内細菌叢改善用組成物。
〔10〕イソキサントフモール及び/又はキサントフモールを対象に摂取させる又は投与する腸内細菌叢改善方法。
〔11〕腸内細菌叢を改善するための、イソキサントフモール及び/又はキサントフモールの使用。
腸内細菌叢改善用組成物は、イソキサントフモール及びキサントフモールのいずれか一方を有効成分として含んでもよく、これらの両方を有効成分として含んでいてもよい。
本発明の一態様において、腸内細菌叢改善用組成物は、イソキサントフモール、又は、イソキサントフモール及びキサントフモールを有効成分として含むことが好ましい。
イソキサントフモール及びキサントフモールは、市販品を使用することもできる。
本発明においては、本発明の効果を奏することになる限り、イソキサントフモール及び/又はキサントフモールを豊富に含む植物由来原料を本発明の組成物に含有させてもよい。
本発明の一態様によれば、腸内細菌叢改善作用を示し、熱に安定であり、健康の維持、増進に資する種々の機能性食品、機能性飲料等を提供することが可能となる。
腸内細菌叢改善用組成物に含まれるイソキサントフモール及び/又はキサントフモールは、例えば、高速液体クロマトグラフィ(HPLC)やLC-MS/MSにより定量することが可能である。イソキサントフモール及びキサントフモールは、簡便に定量分析が可能であり、有効成分の定量分析及び規格化が必要となる機能性表示食品等の有効成分として使用しやすいという利点もある。
腸内細菌叢における善玉菌の存在比率は、例えば、糞便中の細菌の16S rRNA遺伝子解析を行うことにより調べることができる。
腸管バリア機能とは、腸管上皮細胞外(腸管内)から体内への異物(例えば、エンドトキシン等の毒素、起炎物質、未消化物等)の侵入(透過)を防ぐ機能をいう。正常な状態と比べて腸管上皮細胞外から体内への異物の侵入が促進されている状態を、腸管上皮細胞における異物の透過性が上昇した状態と呼ぶ。腸管バリア機能増強とは、腸管上皮細胞における異物の透過性の上昇を抑制すること、及び、腸管上皮細胞における異物の透過性を低下させることのいずれをも意味する。腸管バリア機能増強効果は、例えば、腸管上皮細胞の電気抵抗値(経上皮膜抵抗値(transepithelial electric resistance:TEER))が上昇することによって、又は、TEERの低下を抑制することによって示される。当業者は、目的に応じて腸管バリア機能増強効果の具体的な評価方法を選択することができる。
本明細書で状態又は疾患の予防は、状態又は疾患の発症を防止すること、状態又は疾患の発症を遅延させること、状態又は疾患の発症率を低下させること、状態又は疾患の発症のリスクを軽減すること等を指す。状態又は疾患の改善は、対象を状態又は疾患から回復させること、状態又は疾患の症状を軽減すること、状態又は疾患の進行を遅延させること又は防止すること等を指す。
本発明の腸内細菌叢改善用組成物は、飲食品、医薬、医薬部外品、飼料等の形態とすることができる。本発明の腸内細菌叢改善用組成物は、それ自体が、腸内細菌叢改善のための飲食品、医薬、医薬部外品、飼料等であってもよく、これらに配合して使用される素材又は製剤等であってもよい。
本発明の腸内細菌叢改善用組成物は、一例として、剤の形態で提供することができるが、本形態に限定されるものではない。当該剤をそのまま組成物として、又は、当該剤を含む組成物として提供することもできる。本発明の腸内細菌叢改善用組成物は、腸内細菌叢改善剤ということもできる。
本発明の効果を充分に得る観点から、本発明の腸内細菌叢改善用組成物は、好ましくは経口用組成物である。経口用組成物として、飲食品、経口用の医薬、医薬部外品、飼料が挙げられ、好ましくは飲食品又は経口用医薬であり、より好ましくは飲食品である。
本発明の腸内細菌叢改善用組成物を、飲食品、医薬、医薬部外品、飼料等とする場合、その製造方法は特に限定されず、一般的な方法により製造することができる。また、例えばイソキサントフモールを含む腸内細菌叢改善用組成物は、その製造において、ホップ抽出物を配合し、該ホップ抽出物を加熱する工程を行うことによって製造することもできる。
飲料は、ノンアルコール飲料、アルコール飲料のいずれであってもよい。ノンアルコール飲料として、例えば、茶系飲料、コーヒー飲料、ノンアルコールビールテイスト飲料、炭酸飲料、機能性飲料、果実・野菜系飲料、乳性飲料、豆乳飲料、フレーバーウォーター等が挙げられる。
本発明の腸内細菌叢改善用組成物が茶系飲料である場合、紅茶飲料又は無糖茶飲料であることが好ましい。無糖茶飲料として、緑茶飲料、ウーロン茶飲料、麦茶飲料、玄米茶飲料、ハト麦茶飲料、無糖の紅茶飲料等が挙げられる。
本発明の腸内細菌叢改善用組成物がコーヒー飲料である場合、容器詰コーヒー又はリキッドコーヒーであることが好ましい。
本発明の腸内細菌叢改善用組成物がビール系飲料である場合、発泡酒又は第三のビールであることが好ましい。
本発明の腸内細菌叢改善用組成物がビール及びビール系飲料以外のアルコール飲料である場合、焼酎、チューハイ、リキュール、カクテル、スピリッツ、ウイスキーであることが好ましい。
本発明の腸内細菌叢改善用組成物が機能性飲料である場合、スポーツドリンク、エナジードリンク、健康サポート飲料又はパウチゼリー飲料であることが好ましい。
本発明の腸内細菌叢改善用組成物が乳性飲料である場合、牛乳、ドリンクヨーグルト、乳酸菌飲料又は乳類入清涼飲料であることが好ましい。
本発明の腸内細菌叢改善用組成物が豆乳飲料である場合、豆乳又は大豆飲料であることが好ましい。
本発明の腸内細菌叢改善用組成物を摂取させる対象として、腸内細菌叢改善を必要とする又は希望する対象、腸内環境改善を必要又は希望する対象が好ましい。このような対象として、例えば、過敏性腸症候群、便秘、下痢、食物アレルギーを有するヒト等が挙げられる。本発明の腸内細菌叢改善用組成物は、例えば、腸内細菌叢改善により予防又は改善が期待できる状態又は疾患の予防等を目的として、健常者に対して使用することもできる。
本発明の腸内細菌叢改善用組成物は、天然物や飲食品に含まれる安全性が高い成分を有効成分として含み、継続的に摂取されることによって高い腸内細菌叢改善効果を発揮する。このため本発明の腸内細菌叢改善用組成物は、例えば、上記の過敏性腸症候群、便秘、下痢、食物アレルギーを有するヒト、健常者等が日常的に経口摂取することにより、腸内細菌叢における善玉菌の存在比率を増加させ、腸内細菌叢の改善、腸内環境の改善に使用するための健康食品、機能性表示食品等として有用である。
本発明の一実施態様において、本発明の腸内細菌叢改善用組成物は、上記の表示が付された飲食品であることが好ましい。また上記の表示は、上記の機能を得るために用いる旨の表示であってもよい。
イソキサントフモール及び/又はキサントフモールを対象に摂取させる又は投与する腸内細菌叢改善方法。
イソキサントフモール及び/又はキサントフモールを対象に摂取させる又は投与する腸内環境改善方法。
イソキサントフモール及び/又はキサントフモールを対象に摂取させる又は投与する腸内細菌叢における善玉菌の存在比率の増加方法。
上記方法は、治療的な方法であってもよく、非治療的な方法であってもよい。「非治療的」とは、医療行為、すなわち人間の手術、治療又は診断を含まない概念である。
イソキサントフモール及び/又はキサントフモールを摂取すると、腸内細菌叢における善玉菌の存在比率を増加させることができる。また、腸内細菌叢におけるバクテロイデス(Bacteroidetes)門細菌に対するフィルミクテス(Firmicutes)門細菌の存在比率(Firmicutes門/Bacteroidetes門)を減少させることができる。このような作用により、腸内細菌叢改善、腸内環境改善が可能となる。
腸内細菌叢を改善するための、イソキサントフモール及び/又はキサントフモールの使用。
腸内環境を改善するための、イソキサントフモール及び/又はキサントフモールの使用。
腸内細菌叢における善玉菌の存在比率を増加させるための、イソキサントフモール及び/又はキサントフモールの使用。
上記の使用は、好ましくはヒト又は非ヒト哺乳動物、より好ましくはヒトにおける使用である。使用は、治療的な使用であってもよく、非治療的な使用であってもよい。
本発明は、イソキサントフモール及び/又はキサントフモールを対象に摂取させる又は投与する腸内細菌叢におけるアッカーマンシア(Akkermansia)属細菌の存在比率の増加方法;イソキサントフモール及び/又はキサントフモールを対象に摂取させる又は投与する腸内細菌叢におけるバクテロイデス(Bacteroidetes)門細菌に対するフィルミクテス(Firmicutes)門細菌の存在比率(Firmicutes門/Bacteroidetes門)を減少させる方法;腸内細菌叢におけるアッカーマンシア(Akkermansia)属細菌の存在比率を増加させるための、イソキサントフモール及び/又はキサントフモールの使用;腸内細菌叢におけるバクテロイデス(Bacteroidetes)門細菌に対するフィルミクテス(Firmicutes)門細菌の存在比率(Firmicutes門/Bacteroidetes門)を減少させるための、イソキサントフモール及び/又はキサントフモールの使用、も包含する。
本発明の効果をより充分に得る観点から、イソキサントフモール及び/又はキサントフモールを継続して対象に摂取させる又は投与する場合、2週間以上継続して摂取させる又は投与することが好ましく、8週間以上継続して摂取させる又は投与することがより好ましい。上記方法及び使用においては、1日に1回以上、例えば、1日1回~数回(例えば2~3回)、イソキサントフモール及び/又はキサントフモールを対象に投与又は摂取させればよい。一態様において、上記方法及び使用においては、イソキサントフモール、又は、イソキサントフモール及びキサントフモールを摂取させる又は投与することが好ましい。
また、イソキサントフモール及び/又はキサントフモールは、腸内細菌叢改善のために使用される飲食品、医薬、医薬部外品、飼料等の製造のために使用することができる。本発明は一態様において、腸内細菌叢改善用組成物を製造するための、イソキサントフモール及び/又はキサントフモールの使用、も包含する。
本明細書中に記載された学術文献及び特許文献の全ては、参照として本明細書に組み入れられる。
ホップ抽出物(アサマ化成株式会社製)から、以下の方法でイソキサントフモール及びキサントフモールを単離精製した。すなわち、順相カラムクロマトグラフィー、逆相カラムクロマトグラフィー、分取HPLC精製によりホップ抽出物を原料に、イソキサントフモール及びキサントフモールを精製し、HPLC分析により純度が95%以上であることを確認した。なおHPLC分析においては、カラムとしてDevelosilC30-UG-5(野村化学株式会社)を使用し、検出器の紫外線吸収測定波長は280nm(イソキサントフモール)及び350nm(キサントフモール)とした。得られたイソキサントフモール及びキサントフモールを、それぞれ標品(いずれも純度95%以上)として以下の実験で使用した。
キサントフモール及びイソキサントフモール摂取による腸内細菌叢改善作用の検討
高脂肪食摂取モデルマウスを用いて、腸内細菌叢に与えるキサントフモール及びイソキサントフモールの影響を、以下の手順で検討した。
本試験の群構成(群名、基礎飼料、被験物質及び被験物質の用量)を表1に示す。用量は、体重1kgあたり1日あたりの被験物質の摂取量(mg)である。
なお表中、普通食は「コントロール飼料」(D12450J)を、60kcal%高脂肪食は「超高脂肪飼料」(D12492)(以上、Research Diets社製)を、カテキン類は製剤として「ポリフェノン70A」(製品名、三井農林株式会社製)を使用した。カテキン類は陽性対照として用いた。キサントフモール及びイソキサントフモールは、調製例1で得られた標品(純度95%以上)を使用した。
マウス(C57BL/6J、雄性、7週齢、日本クレア株式会社)を入荷して1週間検疫及び馴化した後、一般状態観察において異常の認められなかった動物より、体重推移を基準に動物を選択した。選択した動物は、馴化期間終了時の体重による層別連続無作為化法により表1に示す群構成中の各群(1群につきn=8)に割り付け、所定の基礎飼料及び水は自由摂取できる状況で飼育を行った。
被験物質を8週間、1日1回経口摂取させた。被験物質の摂取の際には、被験物質と溶媒とを混合した投与液を使用した。溶媒には、0.5重量%カルボキシメチルセルロースナトリウム(CMC)水溶液を使用した。被験物質投与において、マウスに摂取させる液量は10mL/kgとし、最新体重を基準として被験物質量及び液量を算出した。
被験物質摂取開始から8週間後に採取された糞(新鮮便)を解析対象とし、16S rRNA遺伝子解析を行った。16S rRNA遺伝子解析は、特開2018-8911号公報の実施例に記載の方法で行った。この遺伝子解析から、糞に含まれる腸内細菌の存在割合(存在比率)を求め、腸内細菌叢を構成する細菌の存在比率とした。
各群における腸内細菌叢を構成する細菌の存在割合(群平均)を図1に示す。図1に示される存在割合は、糞に含まれる総細菌数に対する各細菌の比率(占有率)である。図1中のVerrucomicrobia(ベルコミクロビウム門)は、アッカーマンシア(Akkermansia)属細菌が属する上位の分類であり、本解析ではアッカーマンシア(Akkermansia)属細菌のみを示す。図1中のイソキサントフモール(IXN)及びキサントフモール(XN)の用量(mg/kg)は、体重1kgあたり1日あたりの被験物質の摂取量(mg)である。キサントフモール又はイソキサントフモールを8週間摂取した個体では、摂取していない個体(表1の群No.2の高脂肪食群)と比較して腸内細菌叢が変化し、アッカーマンシア属細菌の存在割合が増加していた。カテキン類摂取群でも同様の効果が認められた。また、キサントフモール又はイソキサントフモールを上記期間摂取した個体では、高脂肪食群と比較してFirmicutes門細菌/Bacteroidetes門細菌の存在比率の減少が見られた。Firmicutes門細菌/Bacteroidetes門細菌の存在比率は、普通食群では、4.2、高脂肪食群では、7.4、カテキン類群では1.7、キサントフモール(60mg/kg)群では3.2、イソキサントフモール(60mg/kg)群(群No.5)では6.0、イソキサントフモール(180mg/kg)群(群No.6)では2.4であった。
図1は、各被験物質を8週間摂取させた結果であるが、イソキサントフモールを被験物質として群構成及び用量設計を一部変更した試験において、被験物質摂取開始から2週間後に盲腸内容物を採取し、上記と同様に16S rRNA遺伝子解析を行った。被験物質摂取開始から2週間後に、イソキサントフモール(60mg/kg)群(イソキサントフモールを体重1kgあたり1日あたり60mg摂取させた群)で、摂取していない個体(高脂肪食群)と比較して、腸内細菌叢におけるアッカーマンシア属細菌の存在比率の増加が観察された。
Claims (11)
- イソキサントフモール及び/又はキサントフモールを有効成分として含む腸内細菌叢改善用組成物。
- 前記腸内細菌叢改善が、腸内細菌叢における善玉菌の存在比率の増加である請求項1に記載の腸内細菌叢改善用組成物。
- 前記善玉菌が、アッカーマンシア(Akkermansia)属細菌である請求項2に記載の腸内細菌叢改善用組成物。
- 前記腸内細菌叢改善が、バクテロイデス(Bacteroidetes)門細菌に対するフィルミクテス(Firmicutes)門細菌の存在比率(Firmicutes門/Bacteroidetes門)の減少である請求項1に記載の腸内細菌叢改善用組成物。
- 腸管バリア機能増強のために使用される請求項1~4のいずれか一項に記載の腸内細菌叢改善用組成物。
- 飲食品である請求項1~5のいずれか一項に記載の腸内細菌叢改善用組成物。
- 飲料である請求項1~6のいずれか一項に記載の腸内細菌叢改善用組成物。
- 前記飲料が、茶系飲料、コーヒー飲料、アルコール飲料、ノンアルコールビールテイスト飲料、炭酸飲料、機能性飲料、果実・野菜系飲料、乳性飲料、豆乳飲料又はフレーバーウォーターである請求項7に記載の腸内細菌叢改善用組成物。
- 「腸内細菌のバランスを整える」、「腸内環境を良好に保つ」、「腸の健康維持に役立つ」、「腸管バリア機能を高める」、「善玉菌を増やす」、「有用菌を増やす」、「おなかの調子を整える」、「おなかの不快感を軽減する」及び「体質を改善する」の1又は2以上の機能の表示を付した請求項1~8のいずれか一項に記載の腸内細菌叢改善用組成物。
- イソキサントフモール及び/又はキサントフモールを対象に摂取させる又投与する腸内細菌叢改善方法。
- 腸内細菌叢を改善するための、イソキサントフモール及び/又はキサントフモールの使用。
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