JP2003274927A - Method for producing functional food and method for restoring environment by using estrogen-decomposing bacteria - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for separating a microbial community of estrogen-decomposing bacteria, to provide a method for producing a pro-biotic product which diminishes an estrogen- depending tumor risk, an endocrine disruptive risk, etc., by decomposing estrogens widely contained in foods, and to provide a strain of microorganism used for the same. <P>SOLUTION: This method for separating the microbial community of the estrogen- decomposing bacteria comprises enrichingly culturing estriol-utilizing bacteria by adding a microorganism-containing sample which is comparatively highly safe and contains various microorganisms, such as excrement collected from a healthy human body, to a mineral medium in which the estrogen is solely used as a carbon source, separating the enrichingly cultured specific bacteria into a single strain of the bacteria, or consortia of the bacteria, and confirming that the enrichingly cultured bacteria have decomposing activity not only on the estriol but also on 17β-estradiol and estrone and have no pathogenicity. The method for producing the pro-biotic product comprises adding the estorogenic microorganism as it is or an estrogen-decomposing enzyme to foodstuffs, or adding the microorganism or the enzyme to an intestinal ecosystem as an enteric capsule, a suppository, etc., so as to try to diminish an amount of the estrogen in the intestinal ecosystem. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to the estrogen dependence of estrogen (estrone, 17β-estradiol, estriol, etc.), which is widely contained in foods and alcoholic beverages, in the intestinal ecosystem after the food production process or after eating. A method for reducing tumor risk, endocrine disruption risk, etc., and a microbial strain used for that purpose, and at the same time, a method for microbiologically degrading estrogen contained in food wastewater, sewage, etc. to reduce ecosystem disruption risk Regarding

[0002]

2. Description of the Related Art Estrogen is estrone (E1), 1
7β-estradiol (E2), estriol (E
It is a general term for female hormones including 3) and their conjugates. These are substances that are indispensable for maintaining homeostasis in the human body, and recently it has been clarified that brain functions such as sexual motivation are also regulated through estrogen-sensitive neurons. In addition, estrogen deficiency causes not only menopausal disorders but also osteoporosis, hyperlipidemia, arteriosclerosis, and Alzheimer's disease. However, on the other hand, it is also known as an abnormal cell growth promoter for hormone-dependent breast cancer, endometrial cancer, prostate cancer, thyroid cancer, ovarian cancer, uterine fibroids, etc. Hormone therapy such as surgical removal of the pituitary gland, administration of LH-RH analogs that suppress estrogen secretion in the ovary, administration of an inhibitor of aromatase, which is an estrogen producing enzyme, and administration of an antagonist of the estrogen receptor have been carried out. Many therapies other than the administration of antagonists assume that the female hormones present in the human body are mainly of human origin. However, the inventors
In the patent filed (reference number UEDA130925), it is widely used for staple foods such as rice and fruits and vegetables.
1) or 17β-estradiol (E2) was found to be present, and is currently 50 ng / kg (E2).
Allowed daily intake (ADI: Accepta)
It pointed out the necessity of reviewing ble Daily Intake), and at the same time suggested that estrogen derived from these foods may increase the risk of estrogen-dependent breast cancer, uterine cancer, ovarian cancer, etc. Further, as shown in the examples of the present invention, in the present invention, it was found that liquors such as beer also contained estrogen, and conventionally, an increase in free estradiol was observed due to alcohol intake. Taking into account the fact that estrogen in alcohol is one of the causes of alcohol carcinogenesis. Furthermore, in the field of environmental science, it has been pointed out that these female hormones are widely contained in food wastewater, compost, manure, sewage, etc. and may cause ecosystem disruption as endocrine disrupting substances. At present, a method for decomposing female hormones such as water treatment equipment has been applied for a patent by Toto Kikai Co., Ltd. in a wide range of methodologies (Japanese Patent Laid-Open No. 2001-2001
149929), in this patent application, even though there is empirical data on titanium oxide addition and ultraviolet irradiation, the microbial deposit, which is the most important for asserting the rights regarding microorganisms, and the empirical data using microorganisms (Examples) In addition, regarding the decomposition method for microorganisms, the basic conditions for obtaining a patent are not complete. In addition, at present, there is no concept itself regarding the method for producing a functional food using an estrogen-degrading microorganism. In view of such a situation, the inventors have searched for a microorganism group that decomposes estrogen, and a probiotic method using the decomposed microorganism group, a low estrogen beer production method, an environmental purification method, and further, actually. Separated by this method, and FERM P-18782
Have been deposited as Streptomyces (Strep
and a culture of a strain of the genus Tommyces).

[0003]

[Problems to be Solved by the Invention] Currently, a technology for producing low-estrogen foods for estrogen-dependent tumor carriers, etc. and a probiotic technology for attempting estrogen regulation by utilizing the intestinal ecosystem have been developed. It has not been.
Further, the bioremediation technology for degrading estrogen widely contained in wastewater, manure, and sewage by using a specific degrading microorganism is not in the stage of being performed on site. The present invention has been made in consideration of the above circumstances, in food,
It is an object of the present invention to provide an estrogen-decomposing method capable of decomposing and processing estrogen released in the environment or in the intestinal ecosystem, and a strain FERM P-18782 suitable for that purpose.

[0004]

In order to achieve the above object, the method for decomposing estrogen according to the present invention is described in the summary.

As described in the above, it is composed of the following five steps. First, a relatively safe microbial-containing sample containing various microorganisms, such as feces and foods collected from healthy humans, was added to an inorganic medium containing only estriol as a carbon source. Cultivated microbial cells in an integrated culture, the specific cultivated specific microorganisms are separated as a single microorganism or a consortia (a population of microorganisms), and then
Not only estriol, but 17
It is confirmed that β-estradiol and estrone also have the ability to decompose and that they are not pathogenic (step 10
1). To reduce the amount of estrogen in the intestinal ecosystem by adding the estrogen microorganism itself or the estrogen-degrading enzyme to milk beverages, yogurt, beer, etc., or as an enteric coated capsule, suppository, etc. to the intestinal ecosystem. Is used as a probiotic product or the like (step 102). Further, various foods such as beer and shochu are treated with the obtained estrogen-degrading bacterium or its estrogen-degrading enzyme to produce low-estrogen foods (step 103). The estrogen microorganism itself or its estrogen-degrading enzyme is used as food wastewater, a sewage treatment agent, etc. to purify estrogen contamination in the environment (step 104). For these purposes, a culture of a strain of the genus Streptomyces deposited as FERM P-18782 or a microbial strain having a similar function is used (step 105).

[0005]

The present invention will be described in more detail below. First, a microorganism-containing sample containing various relatively safe microorganisms such as feces and foods collected from healthy humans was added to an inorganic medium containing only estriol, which has a relatively high water solubility, as a carbon source. Then, estriol assimilating bacteria are accumulated and cultured, and the accumulated and cultivated specific microorganisms are separated as a single microorganism or a consortia (a group of microorganisms). Next, these accumulated cultivated bacteria are not limited to estriol. It is confirmed that 17β-estradiol and estrone also have the ability to decompose and that they are not pathogenic (step 101). Estrogen added to the inorganic liquid medium,
Since estriol has more hydroxyl groups than estrone or 17β-estradiol, it is easy to disperse in the medium without adding DMSO. In particular, when performing plate culture using a petri dish, a carbon source-free inorganic agar medium (diameter 9
(cm petri dish) spreads 10 mg of estriol evenly and spreads white powder easily, making it easy to confirm colonies after culturing, but in the case of estrone or 17β-estradiol, granular crystals are unevenly distributed on the agar medium. Scattered and not very suitable for assimilating bacteria.

Further, the microorganism-containing sample to be added to the liquid medium is selected as needed. For example, when obtaining degrading microorganisms for use in probiotics, it is desirable to use faeces collected from healthy humans as a separation source.
The reason is that not only is feces originally an environment containing a large amount of estrogen, but it is better to use bacteria that originally settled in the human intestine than to use foreign bacteria obtained from sources other than the intestinal ecosystem. This is because it is presumed that the colonization ability of the bacteria in the intestine is high, and that the bacteria originally existed in the healthy human intestinal ecosystem, it is considered to be advantageous in terms of safety. For the same reason, when the estrogen-degrading bacteria used in the functional food are separated, it is desirable to use the food itself or a sample derived from a healthy human body as the microorganism-containing sample (separation source). Further, in the case of sewage treatment and livestock / human excrement treatment, it is advantageous to separate it from livestock / human excrement or activated sludge from the viewpoint of fixing the added microorganisms.

Next, the enrichment culture will be described in detail.
Using an inorganic liquid medium containing only estriol as a carbon source, aerobically shake-cultured for 1 week, subcultured into a new liquid medium every other week, and repeating the steps several times.
By repeating, microorganisms that cannot assimilate estriol are killed, only microorganisms that can assimilate grow in the liquid medium, and as a result, they are accumulated and cultured. Further, when anaerobic degrading bacteria are desired to be obtained or degrading bacteria capable of growing in a specific pH environment are desired to be obtained, the culture condition (oxygen condition, pH, etc.) may be simply changed to that effect. The estrogen-assimilating bacterium may be any microorganism as long as it is a microorganism capable of assimilating estrogen, or a single species of microorganism,
It does not matter whether they are a group of microorganisms composed of different species.
If you want to obtain a single species of microorganisms, after incubating in liquid medium, inoculate the culture medium on an inorganic agar medium (diameter 9 cm petri dish) excluding carbon source, and apply 10 mg of estriol. It is better to culture for about a week. If colonies cannot be obtained with that, it is highly likely that they are not assimilated as a single species of microorganisms but as synergistic effects of multiple different species of microorganisms, that is, as a consortia. The consortia can be separated by aseptically inoculating the concentrated culture solution of (1) to an agar medium having a nutrient source such as a standard agar medium and culturing. Also,
If necessary, it is also effective to disperse and mix estriol or the like in the upper layer of the agar medium and confirm the halo around the formed colony.

If such an assimilating bacterium such as estriol is cultivated in an integrated manner, the obtained bacterium is used to carry out a stop microbial cell reaction and the like, and not only estriol is obtained by LC / MS / MS method, Confirm that estrone and 17β-estradiol can also be decomposed. After confirmation, the nucleotide sequence of the 16S ribosomal RNA gene is determined and molecular phylogenetic analysis is performed to confirm that it is not a known pathogen species. At the same time, if necessary, further animal experiments are conducted to determine toxicity. Make sure it is not.

Next,

The degrading microorganisms whose safety has been confirmed in the above are cultivated, and freeze-dried bacterial cells, viable cells or estrogen degrading enzyme of the degrading microorganisms are added to milk drinks, yogurt, beer or the like, or enteric-coated capsules. , And is used as a suppository as a probiotic product or the like, which is added to the intestinal ecosystem and attempts to reduce the amount of estrogen in the intestinal ecosystem (step 102). Strictly speaking, if you treat it as a medicine or food for specified health use, after taking it,
It is necessary to confirm whether the added degrading bacteria have settled in the intestinal ecosystem using PCR method or plate culture method, and at the same time, to confirm the fluctuation of estrogen amount in blood, urine, feces, etc. However, when it is treated as a dietary supplement or supplement, that is not required. Probiotic products using these estrogen-degrading bacteria are estrogen-dependent uterine cancer,
Patients suffering from ovarian cancer, uterine fibroids, etc. can be expected to have some therapeutic effect and recurrence preventive effect. If necessary, they may be given to livestock and pets.

Further, as shown in the examples, alcohol such as draft beer may contain estrogen in some cases. Therefore, the obtained estrogen-degrading bacterium or its estrogen-degrading enzyme can be used for various foods such as beer and shochu. To produce a low-estrogen food (step 10).
3). Given the fact that the increase in free estradiol due to alcohol intake has been recognized in the past, these low-estrogen foods annoy some estrogen-dependent tumors such as uterine cancer, ovarian cancer, and uterine fibroids. The patient may have the effect of suppressing estrone-dependent cell proliferation.

Further, in natural / artificial ecosystems such as river water, bottom mud, and sewage, it is not uncommon to detect estrone pollution, and there is concern about disturbance of the ecosystem. Therefore, the estrogen-degrading microorganism itself or the estrogen-degrading enzyme is used as a sewage treatment agent, a food wastewater treatment agent or the like to purify estrogen contamination in the environment (step 104).

[0012] Such an estrogen-degrading bacterium may be any microorganism as long as it is a microorganism that can assimilate estrogen, but the experimental results show that FERM P-1
Streptomyces (S) deposited as 8782
Cultures of strains of the genus Treptomyces are considered effective (step 105). Since this strain is an actinomycete isolated from the feces of a healthy adult male (21 years old) by the method described above, it can be expected to have a certain level of safety. In addition, since it is originally isolated from the human intestinal ecosystem, it is expected to have a higher colonization ability than foreign bacteria, and it is aerobically culturable, which facilitates its handling. Therefore, it is expected to be widely used in the above-mentioned probiotic products and sewage treatment. In addition, conventionally,
Streptomyces Roseochromogenes (Stre
ptomyces rosechromogene
s) has been reported to oxidize estrone by the P450 enzyme (J Steroid Biochem).
Mol Biol, 1999, 15, 153-165,
Steroids, 1990, 55 (9): 39.
0-394, Z Allg Mikrobi
ol, 1977, 17, 507-512). The 16S rDNA sequence data for this actinomycete species is
Since it is not registered in the database, FERM P-
Although the molecular phylogenetic relationship with 18782 has not been confirmed at this time, it is also possible that this species or its related species. However, the point, novelty, and originality of the present invention are that the functional food manufacturing is that "the bacteria having such a function are used for the functional food for estrogen-dependent tumor carriers and the purpose of environmental purification". Law, Environmental Purification Law, etc., but also FERM P-1
8782 is a unique strain isolated from "healthy adult faeces" and is useful in that it has an assimilation capacity that means complete destruction of the steroid skeleton rather than simply oxidizing estriol. Sex does not change at all.

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples.

[0014]

[Example 1] 10 g of feces from a healthy adult male (21 years old)
Was collected and suspended in 90 ml of sterilized water, and 50 ml of Tashiro inorganic liquid medium (34.4 mg of CaCl ₂ .2H ₂ O, MgSO 4) containing only 0.1% estriol as a carbon source.
_{4 · 7H 2 O100mg, NH 4} NO 3 10g, FeC
_{l 2 · 6H 2 O20mg, MnSO} 4 · 5H 2 O2m
_{g, CuSO 4 · 5H 2 O100μg} , ZnSO 4 · 7
H ₂ O 114 μg, H ₃ BO ₃ 10 pg, CoCl ₂ ·
6H ₂ O 100 μg, NiSO ₄ · 6H ₂ O 10 μl,
1 ml of 0.33M phosphate buffer 10 ml: 1 L) was inoculated. After shaking culture at 30 degrees for 1 week, 1 ml
Was collected aseptically and inoculated into a new Tashiro inorganic liquid medium, which was repeated 3 times in total, and accumulated culture was performed for 4 weeks in total. The obtained enriched culture solution was applied to Tashiro inorganic agar medium (diameter 9 cm Petri dish) coated with 10 mg of estriol,
Cultured for 2 weeks. As a result, two types of colonies were confirmed, and it was revealed by an optical microscope that one of them was an actinomycete. The selected bacteria were shake-cultured overnight in a standard nutrient medium in advance, after securing a certain amount of bacterial cells, washed with a carbon source-free Tashiro inorganic liquid medium, and then collected by centrifugation, estrone, After suspending the bacteria in a new Tashiro liquid medium containing 17β-estradiol at the ratios of 300 ng / L and 450 ng / L, respectively, after shaking at 30 ° C. for 12 hours to carry out the resting cell reaction, the resting cell reaction The supernatant obtained by centrifuging the liquid was subjected to solid phase extraction by the method described in detail in the patent filed by the inventors last year (reference number UEDA130925), and the liquid eluted with methanol was subjected to LC / MS / MS.
analyzed. The experiment was carried out in quadruplicate, and as a negative control, a group in which no bacterium was added at the same time was also set, and the decomposition rate of estrone and 17β-estradiol was calculated. As a result, it was confirmed that both strains decomposed 100% of both estrone and 17β-estradiol. Next, after pure culture from each colony, genomic DNA was extracted from the cells. By PCR using the extracted genomic DNA as a template, 16S rRNA gene about 500b
As a result of amplifying p, sequencing the nucleotide sequences, and performing molecular phylogenetic analysis using the neighbor-binding method, the former was found to be a species of Streptomyces (Streptomyces) that is not registered in the existing DNA database.
tomyces sp. ) It is presumed that it is a genus actinomycete and the latter is Acinetobacter baumannii (Acine).
It was presumed to belong to Tobacco baumannii). Of these, the latter is a resident bacterium of humans, but it is also an opportunistic infectious bacterium, so it was subjected to high-pressure sterilization. Since it is known that there are many cases, it is thought that it can be used as a probiotic agent and a food additive, although further safety confirmation by animal experiments and the like is necessary in the future. Therefore, the microorganism was placed in the Patent Biological Depositary Center, National Institute of Advanced Industrial Science and Technology.
Deposited on March 18, 2014 (deposit number FERM P-1878
2) Then, the 16S rDNA nucleotide sequence data used for the phylogenetic analysis was described in the deposit application.

[0015]

Example 2 Next, an example of a method for producing low estrogen beer will be shown. Actinomycete FERM P-18782 was inoculated into 100 m of liquid standard medium, and the cells in the logarithmic growth phase obtained by shaking culture at 27 degrees for 15 hours were collected by centrifugation and added to domestic draft beer that had been previously sterile filtered. Then 3
The reaction was carried out at 0 ° C for 12 hours while shaking the resting cell reaction. Then, after centrifuging to remove the cells, 10 ml of this was taken, 200 ml was filled up with sterilized ultrapure water, and solid phase extraction was performed using Sepppack C18 (Waters) to obtain LC / MS / Quantitative analysis was carried out by the MS method. The experiment was carried out in quadruplicate, and a beer section to which no bacterium was added was also set as a negative control, and the decomposition rate of estrone was calculated. As a result, actinomycetes FERM
It was confirmed that the P-18782-added section decomposed estrone in beer, which was originally 35 ng / L, by 77.1%. Moreover, when the taste was confirmed, no major change was observed. It can be said that the "low estrogen beer" was successfully created on a small scale by the above-mentioned operations, and it was scaled up using a bioreactor or the like, and treated with actinomycete FERM P-18782 at the latter stage of the production process, whereby breast cancer and uterus were treated. It is expected that beer can be produced that reduces the risk of cancer, ovarian cancer, uterine fibroids, etc. The low estrogen beer may be sold after removing the added strain with a sterile filter, but if necessary, it is also possible to sell the beer with an appropriate amount of the deposited actinomycete FERM P-18782 in the beer. . In that case, it is possible to expect the possibility of a probiotic effect in which live bacteria enter the body, and estrogen decomposition proceeds in the intestinal ecosystem. Regarding safety, it has been confirmed that it was originally isolated from the intestinal ecosystem of healthy adult males, and that it is not a known pathogen from 16S rRNA gene sequence analysis,
To be on the safe side, it is safer to further confirm the safety through animal experiments. In addition, this data also suggests that it is not only useful for low-estrogen beer production, but it is also possible to remove estrogen from leftover beer, and it can be used for environmental purification such as food wastewater treatment. To be

[0016]

[Example 3] Deposited actinomycete F in a commercially available milk drink, yogurt
An addition experiment of ERM P-18782 was conducted. Viable bacteria were added to the commercially available milk drink and yogurt, and after 2 weeks, the growth was confirmed by the plate culture method using the Tashiro inorganic agar medium containing only estriol as a carbon source.
A colony of the microorganism was confirmed. Therefore, it is considered that the microorganism can be stably added as a probiotic product to milk drinks, yogurt and the like. In addition, when one of the applicants ate a milk drink or yogurt to which the actinomycete FERM P-18782 was added, no significant change in taste was observed, there was no particular harm to the physical condition, and the health condition was maintained. did it.

[0017]

Example 4

In Example 1, as a microorganism-containing sample, liquid adult culture was carried out in the same manner, using healthy adult female (34 years old) urine instead of healthy adult male (21 years old) feces. As a result, white colonies were obtained on Tashiro agar medium containing only estriol as a carbon source at a high rate of the order of 10 ⁵ CFU / ml (liquid culture solution). Premenopausal women,
Pregnant women, in particular, have very high estrogen excretion and are presumed to have undergone a kind of long-term enrichment culture in the bladder. It is currently believed that the main cause of estrogen pollution in urban ecosystems comes from human female feces, but in treating such biological waste, an enrichment culture was applied from the urine or feces of healthy adult females. The estrogen-utilizing bacteria may function effectively in terms of colonization and safety.

[0018]

Example 5

In Example 1, used as a microorganism-containing sample,
Liquid beer culture was performed in the same manner using draft beer instead of healthy adult male (21 years old) feces,
Yellow bacterial colonies were obtained on Tashiro agar medium containing only estriol as a carbon source. For the purpose of reducing the amount of estrogen in food such as low estrogen beer, when adding microorganisms to food, from the viewpoint of safety and the establishment of added microorganisms, human intestinal bacteria are used, or As described above, after the estrogen-degrading bacteria living in the food itself are separated and cultured, they are added to the food, originally,
The policy of increasing the number of degrading bacteria that lived in the food to activate the food is considered to be advantageous.

As shown in the above-mentioned embodiments, by using the method of the present invention, the estrogen-assimilating bacterium is comparatively selected from the microorganism-containing sample selected according to its individual purpose.
It can be easily separated, but such a thing could not be achieved by the conventional technology. In addition, there has been no concept of low estrogen foods, or even the concept of probiotics that attempts to regulate estrogen levels by utilizing the intestinal ecosystem. Therefore, the present invention is based on the fact that actually isolated actinomycetes FERM.
Claim patent rights not only for P-18782 but also for the estrogen-assimilating bacteria isolation method itself including the selection criteria for microorganism-containing samples, the functional food manufacturing method using the bacterial groups obtained there, and the environmental restoration method. To do.

[0020]

As shown in the examples, the present inventors have succeeded in isolating actinomycetes capable of degrading estrogen from already healthy adult male feces. This strain, or an estrogen-degrading bacteria group that can be isolated using the methodology that isolates this strain, is used as a probiotic product, dietary supplement, or drug to treat estrogen-dependent breast cancer, uterine cancer, ovarian cancer, and uterine fibroids. Incidence rate, mortality rate, recurrence rate, medical expenses may be reduced in the future. In addition, if used in sewage treatment, wastewater treatment, etc., it may be possible to reduce the risk of ecosystem disturbance. Summarizing the above, the present invention, in the future, cancer treatment, preventive medicine, functional food,
It can be concluded that there are potential contributions to society from the four aspects of environmental protection.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 38/46 C12N 1/20 A C12N 1/20 A61K 37/54 F term (reference) 4B018 MD85 MD90 ME07 ME08 MF12 MF13 4B065 AA50X AC20 BA23 BB13 BC01 CA44 4C084 AA01 BA44 CA04 DC22 MA23 MA31 MA37 MA52 MA60 NA14 ZB262 4C087 AA01 AA02 BC22 CA09 MA23 MA31 MA37 MA52 MA60 NA14 ZB26

Claims (7)

[Claims] 1. A relatively safe microorganism-containing sample containing various microorganisms, such as feces and foods collected from healthy humans, is added to an inorganic medium containing only estriol as a carbon source, The estriol-utilizing bacterium is accumulated and isolated, and the accumulated and cultivated specific microorganisms are separated as a single microorganism or a consortia (a group of microorganisms). Next, these accumulated cultivated bacteria are not limited to estriol, but 17β-estradiol. , A method for separating estrogen-degrading microorganisms, characterized by having the ability to decompose estrone and confirming that it is not pathogenic. 2. The estrogen microorganism or estrogen-degrading enzyme is added to milk beverages, yogurt, beer, etc., or added to the intestinal ecosystem as an oral agent or suppository using an enteric capsule, etc. A method of producing a probiotic product that attempts to reduce estrogen levels in an ecosystem. 3. A method for producing a low-estrogen food by treating various foods such as beer and shochu with the obtained estrogen-degrading bacteria group or estrogen-degrading enzyme. 4. Breast cancer, endometrial cancer, prostate cancer, thyroid cancer,
A pharmaceutical / food composition containing an estrogen-degrading microorganism or an estrogen-degrading enzyme as an active ingredient in admixture with a suitable carrier for the prevention or treatment of ovarian cancer, uterine fibroids and the like. 5. A method according to claim 4, which is suitable for oral or rectal administration.
Composition. 6. The composition of claim 4 in the form of a capsule, sachet, suspension, suppository or microenema. 7. FERM P-, which decomposes estrogen
A culture of a strain of the genus Streptomyces deposited as 18782. And a microbial strain having a similar function.