JP7387113B2 - New Lactobacillus lactic acid bacteria - Google Patents

Description

NPMD NITE P-03500 NPMD NITE P-03501 NPMD NITE P-03502

The present invention relates to a novel lactic acid bacteria strain classified as Lactobacillus gasseri and foods, feeds, pharmaceuticals, or cosmetics containing the bacteria.

Lactic acid bacteria are extremely safe microorganisms, and are used in many processed foods, such as fermented dairy products such as yogurt and various pickles, for a variety of purposes, including adding taste and flavor, enhancing nutrition, and improving food preservation. It has been used in In addition, the physiological activities of lactic acid bacteria, such as their ability to protect against pathogens, have attracted attention in recent years, and research is actively underway.

Immune cells such as macrophages, which play an important role in the immune system, recognize molecules such as virus-derived RNA chains and envelopes present on the surface during virus infection using pattern recognition receptors such as Toll-like receptors. It is known to produce type I IFN, represented by interferon (IFN)-β, and type III IFN, represented by λ3.

The IFN produced binds to IFN receptors expressed on surrounding cells. Stimulated cells enhance the expression of RNaseL, which is known as an antiviral protein, through activation of intracellular signal pathways, resulting in a strong infection defense effect around infected cells (non-patent Reference 1). Therefore, in order to prevent and reduce viral infections, there is a need for lactic acid bacteria strains that promote the expression of immune factors such as IFN-β and RNaseL.

Anthony J. Sadler and Bryan R. G. Williams. Interferon-inducible antiviral effectors. Nat Rev Immunol., 8(7):559-568 (2008 ).

Therefore, an object of the present invention is to provide a novel lactic acid bacteria strain classified into the genus Lactobacillus that has a high immunomodulating effect, and foods, feeds, pharmaceuticals, or cosmetics containing the bacteria.

In order to solve the above problems, the inventors of the present invention investigated human-derived lactic acid bacteria and found that certain strains have high They discovered that it has an immunomodulatory effect and completed the present invention.

That is, the novel Lactobacillus lactic acid bacteria of the present invention is characterized by having the following structure.
(1) A lactic acid bacterium of the genus Lactobacillus, which is Lactobacillus gasseri TMT36 strain (accession number: NITE P-03500).
(2) A lactic acid bacterium of the genus Lactobacillus, which is Lactobacillus gasseri TMT39 strain (accession number: NITE P-03501).
(3) A lactic acid bacterium of the genus Lactobacillus, which is Lactobacillus gasseri TMT40 strain (accession number: NITE P-03502).
(4) The lactic acid bacteria of the genus Lactobacillus according to any one of (1) to (3), which is produced by heating at a temperature of 60° C. or higher.
(5) A pharmaceutical composition, food composition, feed composition, or cosmetic composition containing the Lactobacillus lactic acid bacteria according to any one of (1) to (4).

The novel Lactobacillus lactic acid bacteria of the present invention have a high immunomodulatory effect, so ingesting them activates the immune system of the body, making it possible to prevent and/or treat viral infections and other immune diseases. It has this effect.

FIG. 1 is a characteristic diagram in which the expression promoting activity of IFN-β and RNaseL by Lactobacillus gasseri TMT36, 39, and 40 strains was evaluated. FIG. 2 is a characteristic diagram comparing and evaluating the expression promoting activities of IFN-β and RNaseL by non-heated and heat-treated bacterial cells of Lactobacillus gasseri TMT36, 39, and 40 strains. FIG. 3 is a characteristic diagram comparing and evaluating the immunomodulatory effects of heat-treated bacterial cells of Lactobacillus gasseri TMT36, 39, and 40 strains and a comparative strain.

EMBODIMENT OF THE INVENTION Hereinafter, the form for implementing this invention is demonstrated in detail.
<New Lactobacillus lactic acid bacteria>
The novel lactic acid bacterium belonging to the genus Lactobacillus according to the present invention is Lactobacillus gasseri. In particular, among the lactic acid bacteria belonging to Lactobacillus gasseri, Lactobacillus gasseri TMT36, 39, and 40 strains are used.

The Lactobacillus gasseri TMT36, 39, and 40 strains of the present invention were transferred to the Patent Microorganism Depositary of the Japan Institute of Technology and Innovation on July 29, 2021, as NITE P-03500, NITE P-03501, and NITE P-03502. Both have been deposited as .

The morphological characteristics and physiological properties of Lactobacillus gasseri TMT36, 39, and 40 strains of the present invention are shown in Table 1 below.

Physiological properties (sugar assimilation): Table 2 shows the sugar assimilation of this strain and the JCM1131 ^T strain, which is a standard strain of Lactobacillus gasseri.

What should be noted in Table 2 is that the ability to assimilate D-Turanose differs between the TMT36, 39, and 40 strains and the JCM1131 ^T strain. Since the physiological characteristics of the strain did not completely match those of the standard strain, TMT36, 39, and 40 strains were determined to be new lactic acid bacteria strains.

The novel lactic acid bacterium belonging to the genus Lactobacillus according to the present invention uses cells of the lactic acid bacterium and/or a culture containing the cells as an active ingredient. The term "bacterial cells" includes both live and dead cells of the novel lactic acid bacteria of the present invention. In addition, "bacterial cells" may be dry microbial cells obtained by drying live and/or dead microbial cells of the novel lactic acid bacteria of the present invention such as freeze-drying, or wet microbial cells isolated from a culture solution. It may be a bacterial cell fragment obtained by crushing live and/or dead bacterial cells, or it may be a bacterial cell component.

On the other hand, the term "culture" includes a culture solution in which "microbial cells" are cultured, a culture solution treated product obtained by subjecting the culture solution to a predetermined treatment, and the like. Treatments for the culture solution of "microbial cells" include, but are not particularly limited to, drying treatment, heating treatment, bacterial cell killing treatment, enzyme treatment, crushing treatment, filtration treatment, component extraction treatment, and the like. "Cultures" include not only the "bacterial cell" culture fluid itself, but also lyophilized culture fluids, heat-treated culture fluids, and culture fluids that have been irradiated, treated with antibiotics, or treated with chemicals. This includes treated products, processed products in which cell walls are dissolved using a surfactant, and the like. "Culture" may be a culture filtrate obtained by removing live or dead bacteria from a culture solution in which "bacterial cells" have been cultured, or a bacterial suspension in which "bacterial cells" isolated from a culture solution are suspended. A cloudy liquid may be used. The "culture" may be in any form such as solid, powder, granule, paste, or liquid.

The lactic acid bacteria of the genus Lactobacillus of the present invention can be used alone, or two or more types of lactic acid bacteria can be used in combination. It may also be used in combination with other lactic acid bacteria.

Other lactic acid bacteria are not particularly limited, and for example, conventionally known species belonging to the genus Lactobacillus can be widely used. Examples of microorganisms belonging to the genus Lactobacillus include Lactobacillus gasseri, Lactobacillus helveticus, and Lactobacillus acidophilus. lus acidophilus), Lactobacillus delbrookii subsp.・Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus rhamnosus, Lactobacillus johnsonii, Lactobacillus johnsonii Lactobacillus reuteri, Lactobacillus animalis, Lactobacillus・Lactobacillus rhamnosus, Lactobacillus salivarius subspecies ・Lactobacillus salivarius ssp. salivarius, Lactobacillus kefira nofaciens), Lactobacillus paracasei, Lactobacillus fermentum (Lactobacillus fermentum), Lactobacillus kefiranofaciens, Lactobacillus delbrueckii subspecies lactis (Lactobacillus delbrueckii ssp.lactis) ), Lactobacillus amylovorus, Lactobacillus buchneri buchneri), Lactobacillus zeae, Lactobacillus plantarum, Lactobacillus crispatus, and the like.

Lactobacillus gasseri TMT36 (NITE P-03500), TMT39 (NITE P-03501), and TMT40 (NITE P-03502) have excellent immunomodulatory effects. In particular, compared to other Lactobacillus gasseri (eg, Lactobacillus gasseri JCM1131 ^T , etc.), it is characterized by a high ability to induce the expression of immune factors such as IFN-β, IFN-λ3, and RNaseL.

The lactic acid bacteria of the present invention can be cultured under any conditions according to conventional methods for culturing lactic acid bacteria. The culture method is not particularly limited, and conventionally known methods can be appropriately selected and used.

The culture temperature is generally preferably 20 to 43°C, more preferably 37 to 39°C, but other temperature conditions may be used as long as the temperature allows the bacteria to grow. The pH of the medium during cultivation is preferably maintained at 3.0 to 8.0, more preferably 5.5 to 5.8, but other pH conditions may be used as long as the pH allows the bacteria to grow. good. The culture time is usually preferably 12 to 72 hours, but other culture times may be used as long as the time allows the bacteria to grow. The medium for culturing lactic acid bacteria is not particularly limited, but a medium commonly used for culturing lactic acid bacteria can be used. That is, any medium can be used as long as it contains a sufficient amount of nitrogen sources, inorganic substances, and other nutrients in addition to the main carbon source. As the carbon source, glucose, lactose, sucrose, fructose, starch hydrolyzate, blackstrap molasses, etc. can be used. As the nitrogen source, casein hydrolyzate, soybean protein hydrolyzate, potato hydrolyzate, etc. can be used. Other growth promoters that can be used include meat extract, fish extract, yeast extract, and oleic acid.

In particular, the cells of Lactobacillus gasseri TMT36, TMT39 and TMT40 strains and/or the culture thereof according to the present invention are preferably subjected to heat treatment. The expression of immune factors by the heat-treated lactic acid bacteria cells and/or their culture is greatly enhanced compared to before the heat treatment. As a result, the heat-treated cells of each of the lactic acid bacteria and/or their culture can be expected to have superior effects in preventing and alleviating viral infections and other immune diseases.

The heat treatment is not particularly limited, but heating at a temperature of 60°C or higher is preferable, and heating at a temperature of 80 to 100°C is particularly preferable.

Further, the heat treatment time varies depending on conditions such as heating temperature and pressure, but is preferably 0.1 to 60 minutes, more preferably 5 minutes to 40 minutes.

<Pharmaceutical composition>
The lactic acid bacteria according to the present invention can be applied to pharmaceutical compositions, for example. Although the pharmaceutical composition is not particularly limited, it can be formulated and used by mixing it with physiologically acceptable carriers, excipients, binders, diluents, and the like. Specifically, the dosage forms of the pharmaceutical composition according to the present invention include, for example, tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, syrups, suppositories, injections, Examples include ointments, patches, eye drops, and nasal drops. When formulating, additives such as excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, diluents, surfactants, or solvents for injections that are commonly used as pharmaceutical carriers are used. can be used.

In particular, the pharmaceutical composition using the lactic acid bacteria according to the present invention can be administered orally or parenterally. Oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, and suspensions. Parenteral preparations include external preparations (for example, nasal preparations, transdermal preparations, ointments) and suppositories (for example, rectal suppositories, vaginal suppositories). Furthermore, the pharmaceutical composition using the lactic acid bacteria according to the present invention may be used in combination with other medicines, such as immunostimulants, and the timing of administration of the pharmaceutical composition is not particularly limited.

<Food composition>
The use of the lactic acid bacteria according to the present invention can also be applied to food compositions (for humans). Food compositions are not particularly limited, and include, for example, health foods, functional foods, foods for specified health uses, and nutritional supplements. Specific examples of food compositions include various beverages such as juices, soft drinks, tea drinks, drinks, jelly drinks, and functional drinks; alcoholic beverages such as distilled spirits, sake, and beer; cooked rice, noodles, and bread. carbohydrate-containing foods such as rice cakes and pasta; seafood paste products such as kamaboko and chikuwa; processed livestock products such as ham and sausage; retort products such as curry, ankake and Chinese soup; soups; milk, milk drinks, ice cream, and cheese and dairy products such as yogurt; fermented products such as miso, natto, lactic acid bacteria fermented drinks and pickles; Western confectionery such as bean products, biscuits and cookies; Japanese confectionery such as manju and yokan; candies; gums; gummies, jellies and Confectionery such as frozen desserts and frozen desserts such as pudding; instant foods such as instant soup and instant miso soup; foods that can be microwaved; and seasonings such as mayonnaise, dressing, and flavored seasoning liquid.

<Feed composition>
On the other hand, the uses of the lactic acid bacteria according to the present invention are not limited to the above-mentioned human food compositions, but can include feed compositions (feeds or feed additives) given to animals other than humans. . Feed herein means food (including pet food) provided to animals other than humans, and feed additives include supplements for animals other than humans.

Animals to be fed include vertebrates, specifically mammals other than humans, such as primates (monkeys, chimpanzees, etc.), livestock animals (cows, horses, pigs, sheep, poultry, etc.), and pets. Animals (also called "pet animals") (dogs, cats, etc.), laboratory animals (mice, rats, etc.), competition animals (horses, etc.), other reptiles, birds (chickens, etc.), crustaceans (shrimp, crabs, etc.) ), insects (crickets, grasshoppers, etc.), etc.

In addition to the lactic acid bacteria mentioned above, feeds include corn flour, rice flour, rice bran and other grain flours, lees, bran, fish meal, bone meal, fats and oils, skim milk powder, whey, mineral feed, yeast, minerals, and amino acids. , proteins, vitamins, lipids, etc. Specifically, the ingredients listed in the Japan Standard Feed Composition Table (2009 edition, edited by the National Agriculture and Food Research Organization) may be included.

Furthermore, the feed composition may be used as a supplement for animals, particularly pet animals, in the form of tablets or powders, for example.

Alternatively, the feed according to the present invention is a silage obtained by filling a silo with feed crops such as cut green crops or fresh grass and performing lactic acid fermentation with the above-mentioned lactic acid bacteria (for example, Lactobacillus gasseri TMT36, TMT39 and/or TMT40 strains). It may be.

<Composition for cosmetics>
The lactic acid bacteria according to the present invention can also be applied to cosmetic compositions.
"Cosmetics" refers to preparations for use on the skin or mucous membranes that achieve a desired effect by contacting epithelial tissues such as the skin or mucous membranes. The present invention is particularly effective in applications where the composition is brought into continuous contact with the skin or mucous membranes for a long period of time.

The cosmetic composition according to the present invention is blended into cosmetics, but there are no particular restrictions on the cosmetics to which it can be blended, such as lotion, serum, milky lotion, cream, foundation, eye shadow, lipstick, and blusher. , emollient cream, emollient lotion, cream, cream rinse, cold cream, vanishing cream, lotion, pack agent, gel, face pack, soap, body soap, shampoo, conditioner, conditioner, facial cleanser, shaving cream, hair cream, hair lotion , skin or hair cosmetics such as hair treatments, hair packs, glosses, lip balms, and cakes, and oral cosmetics such as toothpastes, moist toothpastes, liquid toothpastes, mouthwashes, and mouth fresheners.

Cosmetics are also included in cosmetics. Cosmetics include cleansing cosmetics, hair cosmetics, basic cosmetics, makeup cosmetics, aromatic cosmetics, sunburn cosmetics, sunscreen cosmetics, nail cosmetics, eyeliner cosmetics, eyeshadow cosmetics, cheeks, lip cosmetics, oral cosmetics, etc. The present invention is effective for any of these applications.

Furthermore, the cosmetic may be a drug or a quasi-drug. For example, the cosmetic composition according to the present invention can be incorporated into an ointment containing pharmaceutically effective ingredients.

When the lactic acid bacteria of the present invention is processed and blended into pharmaceutical, food, feed, and/or cosmetic compositions, the blending ratio of the lactic acid bacteria is not particularly limited, and the ratio of the lactic acid bacteria is not particularly limited. The dosage may be adjusted as appropriate depending on the administration and usage amount. This is determined individually taking into consideration the symptoms, age, weight, intended use, etc. of the person to be administered and used, but for adults, the usual dosage is 1 to 200 g of the lactic acid bacteria culture per day, and the bacterial cells themselves per day. The blending amount may be adjusted to 1.0×10 ¹⁰ to 1.0×10 ¹¹ or 0.001 to 90% as dry weight, and by ingesting it in this way, the desired effect can be achieved. can demonstrate.

The present invention will be explained in more detail below by showing test examples and prescription examples as examples, but these are merely illustrative and the present invention is not limited by these.

<Test Example 1>
IFN-β and RNaseL gene expression promoting effect of novel lactic acid bacteria 1-1. Test method (1) Preparation of new lactic acid bacteria cells Each strain belonging to Lactobacillus gasseri was inoculated into MRS medium (Difco) and cultured at 37°C for 16 hours. After culturing, the cells were washed three times with sterile 0.15 M sodium chloride-0.01 M phosphate buffer (PBS, pH 7.2) and diluted with PBS so that the number of bacteria was 2.5 x 10 ⁹ cells/mL. It was suspended in
(2) Test procedure Next, porcine alveolar macrophages (3D4/31 cells) were suspended in RPMI-1640 medium (Wako) to a concentration of 2.0 x ¹⁰ cells/mL, and this was placed in a 12-well plate. 1 mL of each well was seeded and cultured overnight. After replacing the medium, bacterial cells were added at 5.0 x 10 ⁷ cells/mL and cultured for 2 days. As a control, a well to which PBS was added (denoted as with poly(I:C) in the figure) was prepared. After culturing, the medium was replaced with RPMI-1640 medium supplemented with poly(I:C), an RNA virus mimic, at a concentration of 100 ng/mL, and cultured for 3 and 12 hours.
After stimulation, the cells were washed twice with PBS, TRIzol reagent (Invitrogen) was added to each well, the cell lysate was collected, and RNA was extracted by phenol-chloroform extraction and ethanol precipitation. cDNA was synthesized from the obtained RNA using PrimeScript RT reagent Kit (Takara Bio Inc.).
Using the obtained cDNA as a template, gene expression analysis of IFN-β and RNaseL was performed by quantitative real-time PCR (qPCR) using Platinum SYBR Green qPCR Super Mix-UDG with ROX (Invitrogen). .

1-2. Test results Figure 1 shows that in order to select strains that have the effect of promoting the expression of IFN-β and RNaseL from among new lactic acid bacteria, lactic acid bacteria belonging to Lactobacillus gasseri were added to 3D4/31 cells, and IFN-β and RNaseL were added to 3D4/31 cells. This is the result of analyzing the gene expression level of .
When stimulated with poly(I:C) for 3 hours and 12 hours, Lactobacillus gasseri TMT36, TMT39, and TMT40 strains have a stronger ability to induce IFN-β and RNaseL expression than other strains. Shown.

<Test Example 2>
Effect of heat-treated Lactobacillus gasseri TMT36, TMT39 and TMT40 on promoting IFN-β and RNaseL gene expression 1-1. Test method (1) Preparation of heat-treated bacterial cells Lactobacillus gasseri TMT36, TMT39, and TMT40 strains cultured according to the culture method described in Test Example 1 were heat-treated at 65, 90, or 121°C for 30 minutes, and the number of bacteria decreased to 2. The cells were suspended in PBS to a concentration of .5×10 ⁹ cells/mL.
(2) Test procedure According to the test procedure described in Test Example 1, TMT36, TMT39, or TMT40 strains prepared under each heating condition were added to 3D4/31 cells, cultured for 2 days, and then stimulated with poly(I:C). .
After the stimulation was completed, cDNA was synthesized and gene expression analysis of IFN-β and RNaseL was performed by qPCR method.

1-2. Test results Figure 2 shows the effects of IFN-β in 3D4/31 cells to which heat-treated Lactobacillus gasseri TMT36, TMT39, and TMT40 strains were added in order to examine the heating characteristics of the strain in its ability to induce IFN-β and RNaseL gene expression. This is the result of comparative analysis of the gene expression levels of -β and RNaseL with that of live bacterial cells.
Regarding all the strains, the ability to induce the expression of IFN-β and RNaseL in the heat-treated cells was equal to or higher than that in the live cells. In particular, it was shown that the ability to induce the expression of IFN-β and RNaseL was generally enhanced when heat treatment was performed at 90° C. for 30 minutes.

<Test Example 3>
Comparison of immunomodulatory ability of heat-treated bacterial cells and standard strain 1-1. Test method (1) Preparation of heat-treated bacterial cells According to the culture method described in Test Example 1, the cultured Lactobacillus gasseri TMT36, TMT39, and TMT40 strains were heat-treated at 90°C for 30 minutes, and the number of bacteria was 2.5×. The cells were suspended in PBS to a concentration of 10 ⁹ cells/mL. In addition, Lactobacillus gasseri JCM1131 ^T , which had been heat-treated under the same conditions, was used as a control. Note that in the figure, the heat treatment is indicated as HT (Heat-treated).
(2) Test procedure According to the test procedure described in Test Example 1, heat-treated TMT36, TMT39, or TMT40 strain cells were added to 3D4/31 cells, and after culturing for 2 days, poly(I:C) It stimulated me.
After the stimulation was completed, cDNA was synthesized and the expression of various immune factors was analyzed by qPCR.

1-2. Test Results FIG. 3 shows the results of a comparative analysis of the immunomodulatory ability of heat-treated Lactobacillus gasseri TMT36, TMT39, and TMT40 strains and JCM1131 ^T strain, a standard strain of Lactobacillus gasseri.
All of the heat-treated bacterial cells enhanced various immune factors (IFN-β, IFN-λ3, and RNaseL) compared to poly(I:C) alone, and their activity was higher than that of the standard strain JCM1131 ^T strain. It was also expensive. The above results showed that the immunomodulatory effects of Lactobacillus gasseri TMT36, TMT39, and TMT40 strains were superior to those of other Lactobacillus gasseri strains.

<Prescription example 1>
Production of Lactobacillus gasseri TMT36-containing pharmaceutical composition (granules) Lactobacillus gasseri TMT36 strain was inoculated at 5% by weight into an edible synthetic medium (added with 0.5% yeast extract and 0.1% trypticase peptone). After culturing at 38°C for 15 hours, the bacterial cells were collected by centrifugation. The collected cells were freeze-dried to obtain a freeze-dried powder of the cells. 1 g of this freeze-dried powder was mixed with 5 g of lactose and formed into granules to obtain the pharmaceutical composition (granules) of the present invention.

<Prescription example 2>
Manufacture of Lactobacillus gasseri TMT39-containing pharmaceutical composition (powder) Lactobacillus gasseri obtained in accordance with the provisions of the 13th revised Japanese Pharmacopoeia Explanation General Rules for Preparations "Powder" and in the same manner as in Prescription Example 1 above. 400 g of lactose (Japanese Pharmacopoeia) and 600 g of potato starch (Japanese Pharmacopoeia) were added to 10 g of freeze-dried powder of TMT39 strain and mixed uniformly to obtain a pharmaceutical composition (granules) of the present invention.

<Prescription example 3>
Production of Lactobacillus gasseri TMT40-containing food composition (jelly) 20 g of Lactobacillus gasseri TMT40 strain obtained in the same manner as in Formulation Example 1 above, 2,000 g of fructose, 1,500 g of granulated sugar, 500 g of starch syrup, Mix 100 g of agar, 10 g of fragrance, and 5,870 g of deionized water, stir and mix at 6,000 rpm for 10 minutes using a TK homomixer (TK ROBO MICS; manufactured by Tokushu Kika Kogyo Co., Ltd.), and then heat to 50°C to dissolve. After that, the food composition (jelly) of the present invention was obtained by filling 100 g into containers and cooling.

<Prescription example 4>
Production of Lactobacillus gasseri TMT36-containing food composition (soft drink) 200 mg of Lactobacillus gasseri TMT36 strain obtained in the same manner as in Formulation Example 1 above, 0.75 kg of 50% lactic acid, 5.7 kg of erythritol, fragrance 1 kg of deionized water and 42.55 kg of deionized water were mixed, heated to 40° C., and stirred and mixed for 10 minutes at 6,000 rpm using a TK homomixer (TK ROBO MICS; manufactured by Tokushu Kika Kogyo Co., Ltd.). The food composition (soft drink) of the present invention was obtained by sterilizing this solution at 90° C. for 10 minutes and then cooling it to 10° C. or lower.

<Prescription example 5>
Production of feed composition containing Lactobacillus gasseri TMT39 Soybean meal 12 kg, skim milk powder 14 kg, soybean oil 4 kg, corn oil 2 kg, palm oil 23.2 kg, corn starch 14 kg, wheat flour 9 kg, bran 2 kg, vitamin mixture 5 kg, cellulose 2 The feed composition of the present invention was prepared by blending 10 kg of Lactobacillus gasseri TMT39 strain obtained in the same manner as Formulation Example 1 by blending . Obtained.

The novel Lactobacillus lactic acid bacteria of the present invention have a high immunomodulatory effect, so ingesting them activates the immune system of the living body, making it possible to prevent and/or treat viral infections and other immune diseases. This can be applied to medicines, foods, feeds, cosmetics, etc.

[Reference to deposited biological material]
1. Lactobacillus gasseri TMT36
(a) Name and address of the depositary institution that deposited the biological material concerned: National Institute of Technology and Evaluation (Independent Administrative Agency) Patent Microorganisms Center Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan (zip code 292-0818)
Date of deposit of biological materials with the Depository of Japan July 29, 2021 Accession number NITE P-03500 given by the Depository of Japan regarding the deposit
2. Lactobacillus gasseri TMT39
(a) Name and address of the depositary institution that deposited the biological material concerned: National Institute of Technology and Evaluation (Independent Administrative Agency) Patent Microorganisms Center Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan (zip code 292-0818)
Date of deposit of biological materials with the Depository of Japan July 29, 2021 Accession number NITE P-03501 given by the Depository of Japan regarding the deposit
3. Lactobacillus gasseri TMT40
(a) Name and address of the depositary institution that deposited the biological material concerned: National Institute of Technology and Evaluation (Independent Administrative Agency) Patent Microorganisms Center Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan (zip code 292-0818)
Date of deposit of biological materials with the Depository of Japan July 29, 2021 Accession number NITE P-03502 given by the Depository of Japan regarding the deposit

Claims (6)

Lactobacillus gasseri TMT36 strain (accession number: NITE P-03500) is a lactic acid bacterium of the genus Lactobacillus. Lactobacillus gasseri TMT39 strain (accession number: NITE P-03501) is a lactic acid bacterium of the genus Lactobacillus. Lactobacillus gasseri TMT40 strain (accession number: NITE P-03502) is a lactic acid bacterium of the genus Lactobacillus. A heat-treated bacterial cell of Lactobacillus lactic acid bacteria according to any one of claims 1 to 3, which is produced by heating the Lactobacillus lactic acid bacteria at a temperature of 60° C. or higher. A pharmaceutical composition, food composition, feed composition, or cosmetic composition containing the Lactobacillus lactic acid bacteria according to any one of claims 1 to 3 . A pharmaceutical composition, a food composition, a feed composition, or a cosmetic composition containing the heat-treated bacterial cells of the Lactobacillus genus lactic acid bacteria according to claim 4 .