TW202118495A - Gut microbiota regulating agent - Google Patents

Abstract

An objective of the present invention is to provide a gut microbiota regulating agent that is capable of regulating gut microbiota to a healthy state. In the present invention, a compound having an iridoid skeleton acts to increase the proportions of bacteria of phylum Bacteroidetes and Akkermansia muciniphila and decrease the proportion of bacteria of phylum Firmicutes in the intestinal tract, making it possible to improve the balance of the gut microbiota to a healthy state, and thus can be used as a gut microbiota regulating agent.

Description

Intestinal bacterial flora regulator

The present invention relates to an intestinal flora regulator, which can increase the ratio of bacteria belonging to the phylum Bacteroides and Akkermansia muciniphila, and reduce the ratio of bacteria belonging to Firmicutes ) The ratio of bacteria in the phylum adjusts the intestinal flora into a healthy state.

It has been understood from the development of intestinal bacteriology that the balance of the intestinal bacterial flora is closely related to the maintenance of the host's ecological constancy. The intestinal bacterial plexus interacts closely with mucosal immune cells, nerve cells, endocrine cells, etc. Once it loses its balance, it will become the cause of diseases of the digestive tract, autoimmune diseases, lifestyle diseases, etc. (non-patented References 1 and 2).

In addition, the bacterial flora in the intestine also plays an important role in ingesting food from the host to extract energy to control energy balance. Recent studies have also reported that the composition or change of the bacterial flora in the intestine is related to food-borne obesity that comes with the increase in the activity of AMPK (activated protein kinase) in liver or muscle tissue and the release of the inhibition of fasting-induced adipokines. (Non-Patent Documents 3 and 4).

In addition, it is known that in the healthy intestinal flora, bacteria belonging to the phylum Bacteroides are the advantage, while bacteria belonging to the phylum Firmicutes are the disadvantages. Only reports indicate that once the intestinal tract changes due to changes in dietary life to high-fat foods, etc. Loss of balance in the internal bacterial flora will result in a decrease in bacteria belonging to the phylum Bacteroides, and an increase in bacteria belonging to the phylum Firmicutes, resulting in an increase in insulin resistance (Non-Patent Documents 5 and 6). Furthermore, it has also been understood that the Ekman muciniphils in the intestinal bacterial flora play an anti-inflammatory effect and play an important role in maintaining a healthy intestinal environment.

In recent years, due to the disorder of dietary life and the increase of high-fat foods, the balance of the intestinal bacterial flora is disordered, the ratio of bacteria belonging to the phylum Bacteroides and Ekman mucophila has decreased, and the bacteria belonging to the phylum Firmicutes The number of people with increasing rate is increasing, and it is hoped to develop materials that can improve the balance of the bacterial flora in the intestines.

Prior art literature Non-patent literature Non-Patent Document 1: Lakshminarayanan B et al., Compositional dynamics of the human intestinal microbiota with aging: implications for health. J Nutr Health Aging 18: 773-86, 2014 Non-Patent Document 2: Shinji Fukuda, etc., Intestinal Ecosystem and Anti-aging: Anti-aging Medicine 9:717-722,2014 Non-Patent Document 3: Backhed F et al., The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci 101: 15718-15723, 2004 Non-Patent Document 4: Hildebrandt MA et al., High-fat diet determines the composition of the murine gut microbiome independently of obesty, Gastroenterology 137:1716-1724. 2009. Non-Patent Document 5: Ley RE et al., Obesity alters gut microbial ecology. Proc Natl Acad Sci 102:11070-11075, 2005 Non-Patent Document 6: Turnbaugh PJ et al., Anti obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444;1027–1031, 2006

The problem to be solved by the invention The object of the present invention is to provide an intestinal bacterial flora adjusting agent capable of adjusting the intestinal bacterial flora to a healthy state.

In order to solve the aforementioned problems, the present inventors conducted careful investigations and found that compounds with iridoid skeletons can increase the ratio of bacteria belonging to the phylum Bacteroides and Ekman muciniphila in the intestines, and increase the ratio of bacteria belonging to Firmicutes. The effect of reducing the ratio of bacteria in the phylum can make the balance of the intestinal bacterial flora in a healthy state. The present invention is based on the knowledge that has been completed through further investigations.

That is to say, the present invention provides the following inventions in the aspects disclosed. Item 1. "An intestinal bacterial flora regulator containing a compound having an iridoid skeleton. Item 2. "The intestinal flora regulator as described in Item 1, wherein the compound having an iridoid skeleton is selected from the group consisting of asperuloside, geniposide acid, and eucommia (eucommiol), 1-deoxyeucommiol, epieucommiol, asperulosidic acid, deacetyl asperulosidic acid, chicken feces It is composed of scandoside 10-O-acetate, aucubin, eucomoside A, eucomoside B, and eucomoside C At least 1 in the group. Item 3. The intestinal bacterial flora regulator as described in Item 1 or 2, which is a food or drink or an internal medicine. Item 4. 　 The intestinal flora regulator as described in any one of items 1 to 3, which is used to increase the ratio of bacteria belonging to the phylum Bacteroides and Ekman muciniphila in the intestines, and to make the genus The ratio of bacteria in Firmicutes is reduced. Item 5. "Use of a compound having an iridoid skeleton for the manufacture of an intestinal flora regulator. Item 6. "The use as described in Item 5, wherein the aforementioned compound having an iridoid skeleton is selected from the group consisting of trisoside, geniposide, eucommol, 1-deoxyeucommiaol, epieucommol, At least one of the group consisting of trifolate, deacetyl trifolate, cephaloside 10-O-acetate, corallin, eucommia glucoside A, eucommia glucoside B, and eucommia glucoside C 1 kind. Item 7. "The use as described in Item 5 or 6, wherein the aforementioned intestinal bacterial flora regulator is a food or drink or an internal medicine. Item 8. "The use as described in any one of items 5 to 7, wherein the aforementioned intestinal flora adjusting agent is used to increase the ratio of bacteria belonging to the phylum Bacteroides and Ekman muciniphila in the intestine, and Reduce the rate of bacteria belonging to Firmicutes. Item 9. "A method for adjusting the intestinal flora, which is to administer or ingest a compound with an iridoid skeleton to those who need to adjust the intestinal flora. Item 10. "The method for adjusting the intestinal flora as described in Item 9, wherein the compound having an iridoid skeleton is selected from the group consisting of trisoside, geniposide, eucommia alcohol, 1-deoxyeucommia Alcohol, Epi-Eucommia Alcohol, Trifoglylic Acid, Deacetylated Carbyl Glycoside, Crytoside 10-O-Acetate, Coraloside, Eucommia Glycoside A, Eucommia Glycoside B, and Eucommia Glycoside C Make up at least one of the groups. Item 11. "The method for adjusting the intestinal flora as described in Item 9 or 10, wherein the agent for adjusting the intestinal flora is a food or drink or an internal medicine. Item 12. 　The method for adjusting the intestinal flora as described in any one of items 9 to 11, which increases the ratio of bacteria belonging to the phylum Bacteroides and Ekman muciniphila in the intestines, and makes them thick The ratio of bacteria in the phylum Hypobacteria is reduced. Item 13. "A non-therapeutic use of a compound with an iridoid skeleton, which is used to adjust the bacterial flora in the intestine. Item 14. 　 The non-therapeutic use as described in Item 13, wherein the aforementioned compound having an iridoid skeleton is selected from the group consisting of trisoside, geniposide, eucommiaol, 1-deoxyeucommiaol, table The group consisting of eucommia alcohol, tributylic acid, deacetyl tributylic acid, tenoside 10-O-acetate, coralline, eucommiacoside A, eucommiacoside B, and eucommiacoside C At least one of them. Item 15. 　The non-therapeutic use as described in Item 13 or 14, which is used to increase the ratio of bacteria belonging to the phylum Bacteroides and Ekman muciniphila in the intestine, and to increase the ratio of bacteria belonging to the phylum Firmicutes The ratio of bacteria decreases. Item 16. "A compound with an iridoid skeleton, which is used for the treatment of the adjustment of the bacterial flora in the intestine. Item 17. "The compound as described in Item 16, wherein the aforementioned compound having an iridoid skeleton is selected from the group consisting of trisoside, geniposide, eucommiaol, 1-deoxyeucommiaol, epieucommiaol, At least one of the group consisting of trifolate, deacetyl trifolate, cephaloside 10-O-acetate, corallin, eucommia glucoside A, eucommia glucoside B, and eucommia glucoside C 1 kind. Item 18. "The compound as described in Item 16 or 17, which is used to increase the ratio of bacteria belonging to the phylum Bacteroides and Ekman myxoplasma, and to decrease the ratio of bacteria belonging to the phylum Firmicutes.

Invention effect The intestinal bacterial flora adjusting agent of the present invention increases the ratio of bacteria belonging to the phylum Bacteroides and Ekman muciniphila, and reduces the ratio of bacteria belonging to the phylum Firmicutes, thereby enabling The balance of the intestinal bacterial flora is in a healthy state, so it is beneficial to the soundness of the intestinal environment, the maintenance of a sound intestinal environment, and the prevention, treatment or prevention of symptoms or diseases caused by the insufficiency of the intestinal environment. Improvement etc.

The intestinal bacterial flora regulator of the present invention is characterized by containing a compound having an iridoid skeleton. Hereinafter, the intestinal flora adjusting agent of the present invention will be described in detail.

[Compounds with iridoid skeleton] The intestinal flora regulator of the present invention contains a compound having an iridoid skeleton (hereinafter also referred to as "iridoid compound") as an active ingredient.

The iridoid compounds are limited to those that are edible or pharmaceutically acceptable, and their types are not particularly limited, and examples include trifoside, geniposide, eucommol, and 1-deoxyeucommia , Epi-Eucommia Alcohol, Trifoglylic acid, Deacetylcosyl Glucoside, Crytoside 10-O-acetate, Coral wood, Eucommia Glucoside A, Eucommia Glucoside B, Eucommia Glucoside C, etc. These iridoid compounds may be used individually by 1 type, and may be used in combination of 2 or more types.

Among these iridoids, the effect of increasing the ratio of bacteria belonging to the phylum Bacteroides and Ekman muciniphila and reducing the ratio of bacteria belonging to the phylum Firmicutes is further improved. In view, trifoside and geniposide are preferred, and trifoside is preferred.

The iridoid compound used in the present invention may be derived from natural products, or may be chemically synthesized. Furthermore, the iridoid compound used in the present invention may be either a purified product or a crude product.

Preferred examples of iridoid compounds used in the present invention include purified or crude iridoid compounds derived from natural products, and processed products of natural products containing iridoid compounds.

Examples of natural products containing iridoid compounds such as trifoside include plants such as Eucommia ulmoides, Plantago lanceolata, Morinda citrifolia. The plant can be cultivated and produced, or it can be naturally collected. The plant parts used are not limited as long as they contain iridoid compounds, and any plant, flower, fruit, leaf, branch, bark, rhizome, or seed can be used. In the case of Eucommia ulmoides, it should be exemplified as leaves; in the case of psyllium, seeds should be used; in the case of Morinda citrifolia, leaves should be used.

The processed products of natural products containing iridoid compounds specifically include dried products, pulverized products (including raw materials and dried products), and extracts of the aforementioned natural products. Among the processed materials, extracts are suitable. In addition, the extract may be any of non-concentrated extracts (non-concentrated products), viscous extracts (ie liquid concentrates), and extract powders (ie dried products).

In the processing of natural products containing iridoid compounds, it is easy to include a predetermined amount of iridoid compounds, and Eucommia ulmoides leaf extract is preferable. For example, eucommia leaves can be extracted in their original raw state or after pre-treatments such as crushing, cutting, steaming, rolling, drying, roasting, etc., if necessary, to obtain eucommia leaves extract . In terms of extraction treatment, it is sufficient to use general extraction methods used in the production of plant extracts, and examples thereof include solvent extraction treatment, supercritical extraction treatment, and steam distillation treatment. Among them, solvent extraction treatment is preferable.

烷、乙腈、乙酸乙酯等酯類；二甲苯、苯、氯仿等)、其等之混合液，宜可舉水、低級醇、其等之混合液，較佳可舉溫水、熱水等加熱水，更佳可舉熱水。該等溶劑可單獨使用1種，亦可組合2種以上使用。The extraction solvent used in the solvent extraction treatment of eucommia leaf extract can include water (including warm water and hot water), organic solvents (methanol, ethanol, n-propanol, isopropanol, n-butanol, etc.) The lower alcohols; propylene glycol, 1,3-butanediol and other polyols; acetone and other ketones; diethyl ether, two

Esters such as alkane, acetonitrile, ethyl acetate; xylene, benzene, chloroform, etc.), mixtures thereof, preferably water, lower alcohols, and mixtures thereof, preferably warm water, hot water, etc. Heating water, preferably hot water. These solvents may be used individually by 1 type, and may be used in combination of 2 or more types.

The specific extraction conditions in the solvent extraction treatment of eucommia leaf extract are not particularly limited as long as the iridoid compounds can be extracted. For example, when water is used as the extraction solvent, a method of immersing in water can be mentioned. During the dipping, stirring can also be carried out as needed. The amount of water can be adjusted to a ratio of 10 to 800 parts by weight relative to 1 part by weight of eucommia leaves (dry weight basis), and is preferably 10 to 700 parts by weight, preferably 10 to 500 parts by weight. The water temperature during the extraction may be, for example, about 20-100°C, and preferably about 70-98°C; the extraction time may be about 1-60 minutes, and preferably 5-40 minutes, preferably 10-40 minutes. After that, the solid matter can be removed by performing solid-liquid separation to obtain an extract. As the solid-liquid separation method, conventional methods can be used, and examples thereof include filtration or centrifugal separation. In addition, the leaves of Eucommia ulmoides that have been subjected to an extraction process can also be subjected to an extraction process again.

The extract obtained from the extraction treatment can also be filtered and adsorbed as needed to improve the purity of the iridoid compounds; the aforementioned adsorption treatment uses a polystyrene colloid filled with polystyrene (polystyrene-divinyl Benzene copolymer, etc.), ion exchange resin, activated carbon and other carrier column chromatography methods. The extract obtained from the extraction process can be used directly in the state of non-concentrated extract without the concentration step, and can also be used in the state of the viscous extract in the step, or it can be used in the drying step for extraction. The state of powder is used.

[Dosage Form/Form/Use] The dosage form of the intestinal bacterial flora adjusting agent of the present invention is not particularly limited, and it may be any of solid, semi-solid, or liquid.

The intestinal bacterial flora adjusting agent of the present invention may be in a form that can be transferred into the intestine. Although it is preferably in the form of oral ingestion or oral administration, it may also be in the form of intestinal administration.

The form of the intestinal bacterial flora adjusting agent of the present invention specifically includes food and beverages and internally administered drugs (including internally administered quasi-drugs).

When the intestinal flora regulator of the present invention is in the form of a food or drink (that is, when it is provided as a food or drink for preventing Alzheimer's disease), the iridoid compound is directly or combined with other food materials or What is necessary is just to add a combination of components and prepare it in a desired form. Such food and beverages, in addition to general food and beverages, include foods with health functions (including foods for specific health uses, foods with nutritional functions, supplements, etc.), foods for patients, and other foods. The form of such foods and drinks is not particularly limited, and specific examples include tea beverages, nutritious beverages, fruit juice beverages, carbonated beverages, lactic acid beverages, and other beverages; capsules (soft capsules, hard capsules), tablets, granules, powders , Jelly, liposome preparations and other supplements; jelly, candy, jelly and other hobby products. Among the food and beverages, beverages are preferably cited, preferably tea beverages containing eucommia tea extract.

When the intestinal bacterial flora regulator of the present invention is made into a preparation form of an internally administered drug (including an internally administered quasi-drug), the iridoid compound can be directly or combined with other additives to prepare the desired form. can. Such internal medicines include, specifically, drinking, lozenges, pills, powders, fine granules, granules, lozenges, capsules (including hard capsules and soft capsules), lozenges, chewables, Extracts (including viscous extracts, dry extracts, etc.), jelly, syrup, alcohol, elixirs, liposome preparations, etc.

In the intestinal bacterial flora regulator of the present invention, the content of iridoid compounds can be based on the iridoid compound in consideration of the subject’s physique, age, intestinal environment, the form of the intestinal bacterial flora regulator, etc. The daily intake/dosing amount can be appropriately set. The daily intake/administration amount of iridoid compounds can be set to be about 15-500 mg based on the total amount of iridoid compounds, preferably about 30-300 mg, preferably about 50-150 mg. The intestinal bacterial flora adjusting agent of the present invention can be taken or administered once a day, or divided into multiple times a day, but it is preferably 1 to 3 times a day.

More specifically, when the intestinal flora regulator of the present invention is made into the form of a beverage preparation, the content of iridoid compounds may be, for example, about 0.00075 to 1% based on the total iridoid compounds, And it is preferably about 0.0015 to 0.6% by weight, more preferably about 0.0025 to 0.3% by weight.

In addition, when the intestinal bacterial flora regulator of the present invention is made into solid preparations such as tablets, pills, powders, granules, granules, capsules, mouthpieces, and chewables, iridoids The content of the compound may be, for example, about 5 to 95% by weight based on the total amount of iridoid compounds, preferably about 10 to 80% by weight, and more preferably about 15 to 65% by weight.

The intestinal bacterial flora adjusting agent of the present invention has the effect of increasing the ratio of bacteria belonging to the phylum Bacteroides and Ekman muciniphila, and reducing the ratio of bacteria belonging to the phylum Firmicutes, and can be used for adjustment The intestinal bacterial colony adjusts the balance of the intestinal bacterial colony to a healthy state. That is, in one form of the intestinal flora adjusting agent of the present invention, it is possible to target those with a low ratio of bacteria belonging to the phylum Bacteroides to bacteria belonging to the phylum Firmicutes in the intestinal flora. Here, the so-called "the ratio of bacteria belonging to the phylum Bacteroides in the intestinal flora is low to bacteria belonging to the phylum Firmicutes", for example, in the intestinal flora, the ratio of bacteria belonging to the phylum Bacteroides to Firmicutes The ratio is 0.6 or less, and preferably 0.05 to 0.6, preferably 0.05 to 0.5, more preferably 0.05 to 0.3, particularly preferably 0.05 to 0.2.

By keeping the balance of the intestinal bacterial clusters in a healthy state, the mucus covering the intestinal epithelial cells can be maintained in a healthy state, and as a result, the immune function of the living body can be increased. Therefore, the intestinal bacterial clusters regulator of the present invention can be used In the use of hyperimmune function of living body, etc. That is, in one aspect of the intestinal bacterial flora adjusting agent of the present invention, it is possible to target, for example, persons requiring hyperimmune function, persons with low immune function, and the like. In addition, the intestinal bacterial flora regulator of the present invention can also be used for the prevention, treatment or improvement of symptoms or diseases caused by the insufficiency of the intestinal environment. That is, one of the forms of the intestinal bacterial flora regulator of the present invention may also target the following: those with insufficiency in the intestinal environment, and diseases or symptoms caused by the insufficiency of the intestinal environment as one of the causes Treat those in need.

In addition, since high-fat foods will cause the ratio of bacteria belonging to the phylum Bacteroides to decrease and the ratio of bacteria belonging to the Firmicutes phylum to increase. Such changes in the flora of the intestinal flora, so the intestinal flora regulator of the present invention can also be used It is used for the purpose of suppressing the changes in the bacterial phase of the intestinal bacterial flora caused by the intake of high-fat foods. Here, the so-called high-fat food is a food in which the proportion of fat in the total energy intake (fat weight ratio) is 30% or more. That is, one form of the intestinal bacterial flora adjusting agent of the present invention is, for example, administered or ingested within 2 hours before ingestion of high-fat food and/or within 2 hours after ingestion of fatty food.

In addition, the intestinal bacterial flora plays a role of extracting energy from the host's intake of food to control energy balance. Therefore, the intestinal bacterial flora adjusting agent of the present invention can also be used for the purpose of optimizing the energy consumption of ingesting food.

Furthermore, the intestinal bacterial flora adjusting agent of the present invention can also be used as a ratio increasing agent for bacteria belonging to the phylum Bacteroides in the intestinal bacterial flora, a ratio increasing agent for Ekman muciniphila in the intestinal bacterial flora, Agents for reducing the ratio of bacteria belonging to Firmicutes in the intestinal flora, etc.

Example Examples are shown below to more specifically illustrate the present invention, but the present invention is not limited by them.

Test example 1 Five-week-old male mice (C57/6J, Charles River Co., Ltd., Japan) were divided into three groups, and the mice in each group were fed with the feed of the composition shown in Table 1 for 12 weeks.

[Table 1]

After bred for 11 days, each mouse was dissected, the cecum content was collected, and the bacterial ratio of the intestinal bacterial flora was analyzed by the following method. First, the collected cecal contents were freeze-dried, and 100 mg of 3mm zirconia beads and 400 μL of 1% by weight Tris-EDTA buffer containing sodium lauryl sulfate, and phenol/chloroform/isoamyl alcohol (volume Ratio 25:24:1) mixed solvent 400μL, use SHAKEMASTER and shake at 1500rpm for 15 minutes. The resulting suspension was separated by a centrifuge at 17,800 g for 5 minutes at 4°C, and DNA was recovered. Then use RNase A to remove RNA. Next, the obtained DNA sample is treated with the above-mentioned mixed solvent of phenol/chloroform/isoamyl alcohol (volume ratio 25:24:1) to purify the sample.

The 16SrRNA gene in the obtained DNA sample was analyzed by the following method. First, the V1-V2 region of the 16S rRNA gene was amplified using the primers shown in Table 2 from the obtained DNA. The polymerase reaction system was carried out at 98°C for 1 minute for 1 cycle, and then at 98°C for 10 seconds, 55°C for 15 seconds and 68°C for 30 seconds for 20 cycles, and then a 68°C for 3 minutes extension reaction.

[Table 2]

Next, the resulting PCR product was purified using the Agenvourt AMPure XP kit (Beckman Coulter Co., Ltd.). Then, the purified sample was amplified using the pre-set primer containing the P5 sequence and the reverse primer containing the P7 sequence shown in Table 3 to obtain a PCR product.

表中之序列中，N為因應index之特定鹼基。[table 3]

In the sequence in the table, N is the specific base corresponding to the index.

The resulting PCR products were sequenced with MiSeq (Illumina company). The obtained 16SrRNA sequence was first used to splice the paired-end read using software (FLASH, https://ccb.jhu.edu/software/FLASH/, Johns Hopkins University the Center for Computational Biology) . Remove the combined read fragments whose quality score is less than 25, and output the file. Then, the read fragments that have more than 97% identical sequences to each known bacterial sequence (reference sequence) contained in the database are compiled into an Operational Taxonomic Unit (OTU). The read fragments were processed using a global genomics analysis program (QIIME, http://qiime.org/home_static/dataFiles.html, North Arizona University, Pathogen and Microbiome, Knight and Caporaso labs.). The obtained OTU data is statistically processed using online analysis software (Microbiome analyst, https://www.microbiomeanalyst.ca/MicrobiomeAnalyst/faces/home.xhtml).

The results obtained are shown in Tables 4 and 5. Compared with the control food group, the high-fat food group had a lower ratio of bacteria belonging to the phylum Bacteroides, while the ratio of bacteria belonging to the phylum Firmicutes increased. In contrast, compared with the control food group, the high-fat food + trisoside group had an increase in the ratio of bacteria belonging to the phylum Bacteroides and a decrease in the ratio of bacteria belonging to the phylum Firmicutes. In addition, in the control food group and the high-fat food group, Ekman Muciniphila was below the detection limit, but in the high-fat food + trifocin group, the presence of Ekman Muciniphila was detected. From the above results, it was confirmed that trichoside has the effect of making the balance of the intestinal bacterial flora in a healthy state.

[Table 4]

[table 5]

Test Example 2 Nine subjects (men and women with a BMI value of 25-30 and 40 years of age or more) ingested the tablets of the composition shown in Table 6 once a day for 4 weeks. [Table 6]

Before the ingestion of the tablets and 8 weeks after the start of ingestion, the subjective symptoms shown in Table 7 were consulted, and the diagnosis was conducted in 5 stages from 1 to 5 points (1 none at all, 2 almost none, 3 little, 4 moderate, 5 high ) Commentary. In this standard, it can be judged that points 1 and 2 are no problem, point 3 is symptom-prone but is observational guidance, and points 4 and 5 are required for treatment. In addition, the subjective symptoms shown in Table 7 are all those that can be expected to be improved by the side effects of the intestinal bacterial flora adjustment action.

Table 7 shows the average value of the points of symptoms felt by the subjects. This result suggests that by ingesting trisoside and geniposide, the balance of the bacterial flora in the intestines will be improved and become healthy.

[Table 7]

Prescription example The daily intake of foods and beverages or internal medicines containing iridoid compounds as shown in Tables 8 to 10 can be expected to improve the balance of the intestinal bacterial flora to a healthy state.

[Table 8]

[Table 9]

[Table 10]

(no)

Claims (4)

The use of a compound with iridoid skeleton, which is used to manufacture intestinal bacterial flora regulator. The use of claim 1, wherein the aforementioned compound with iridoid skeleton is selected from asperuloside, geniposide acid, eucommiol, 1-deoxyeucommia Alcohol (1-deoxyeucommiol), Epieucommuniol (epieucommiol), Asperulosidic acid, Deacetyl asperulosidic acid, Deacetyl asperulosidic acid, Deacetyl asperulosidic acid, 10-O-acetate ( At least one of the group consisting of scandoside 10-O-acetate, aucubin, eucomoside A, eucomoside B, and eucomoside C. Such as the use of claim 1 or 2, wherein the aforementioned intestinal bacterial flora modifier is a food or drink or an internal medicine. Such as the use of claim 1 or 2, wherein the aforementioned intestinal flora modifier is used to increase the ratio of bacteria belonging to the phylum Bacteroides and Akkermansia muciniphila in the intestine, and Reduce the ratio of bacteria belonging to Firmicutes.