JP2018174772A - Methods for producing lactic acid bacteria, and compositions for immunity modulation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide methods for preparing lactic acid bacteria having an activity to elicit IL-10 production that suppresses excess immune response but almost no activity to elicit IL-12 production that induces excess immune response, as well as immunity modulating compositions comprising the bacteria as an effective ingredient.SOLUTION: A lactic acid bacterial strain, whose IL-10 production-eliciting activity remains but IL-12 production-eliciting activity is almost lost, is prepared by culturing a lactic acid bacterial strain belonging to Lactobacillus pentosus having IL-10 production-eliciting and IL-12 production-eliciting activities with addition of an alkaline agent to suppress pH reduction during culture.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a method for producing lactic acid bacteria in which the activity to induce IL-10 production remains and the activity to induce IL-12 production has almost disappeared, and to a composition for immunomodulation.

  It is known that some microorganisms such as lactic acid bacteria have the effect of improving the immune activity of the living body, in addition to the effect of improving the balance of intestinal flora to reduce intestinal rotten products and improving fecal properties. . Regarding the mechanism of immune activation by microorganisms, the ingested microorganisms pass through the stomach and enter the small intestine, and the microorganisms are taken up by endocytosis from M cells on the surface of Peyer's patches present on the mucosa covering the small intestine, It is considered that T cells are activated by dendritic cells in contact with the membrane side receiving and degrading microorganisms and presenting their antigen fragments to T cells. These T cells differentiate into Th1 cells, Th2 cells, Th17 cells, and Treg cells depending on the type of signal emitted by dendritic cells.

  Among these, Th1 cells produce cytokines such as IFNγ and IL-12, attack and destroy foreign substances such as bacteria and viruses to prevent infection, and further activate macrophages. Here, IL-12 is a cytokine that is also secreted from antigen-presenting cells such as dendritic cells and macrophages, and is a natural killer cell (NK cell) that directly attacks cancer cells, and killer T cells (CTL cells). It is known as a very potent immunoactive substance that activates and enhances the production of IFNγ.

  In addition, Treg cells produce cytokines such as TGFβ and IL-10, and suppress the activation of macrophages and dendritic cells. Here, IL-10 is a cytokine which is also secreted from Th2 cells, monocytes, macrophages and the like, and suppresses the production of IL-1, IL-6, IL-12, TNFα from macrophages, IFNγ It is known as an immunosuppressant that suppresses production.

  As described above, IL-12 has a negative aspect in that it causes an excessive immune response that also attacks normal tissues and cells that constitute itself as well as the positive aspect of activation of inflammatory response and immune response. On the other hand, IL-10 is considered to have a negative function of suppressing the immune response as well as having a positive function of suppressing an abnormal or excessive immune response to self.

  Patent Document 1 describes that lactic acid bacteria belonging to a specific Lactobacillus helveticus can be used as an immune disease preventive agent that induces a high IL-10 / IL-12 ratio.

Unexamined-Japanese-Patent No. 2015-082164

  According to the example, the IL-10 / IL-12 production ratio of the preventive agent for immune diseases described in Patent Document 1 is estimated to be about 3 to 5.5. However, in order to suppress an abnormal or excessive immune response, an immunomodulatory composition that can achieve an even higher IL-10 / IL-12 production ratio is desirable.

  An object of the present invention is a lactic acid bacterium in which production-inducing activity of IL-10 having a function of suppressing excessive immune response remains, and in which production-inducing activity of IL-12 having a function of causing excessive immune response has disappeared. A method for producing a lactic acid bacterium to be produced, and a composition for immunomodulation comprising the lactic acid bacterium as an active ingredient.

  In order to achieve the above object, as a result of various researches by the present inventors, in specific lactic acid bacteria, IL-10 production can be achieved by culturing while adding an alkaline agent so as to suppress a drop in pH accompanying the culture. Although the induction activity remained, it was found that the IL-12 production induction activity was almost lost, and the present invention was completed.

  That is, the first aspect of the present invention belongs to Lactobacillus pentosus, and an alkaline agent is added so as to suppress the decrease in pH accompanying the culture with the lactic acid bacteria having IL-10 production inducing activity and IL-12 production inducing activity. According to the invention, there is provided a method for producing a lactic acid bacterium, which comprises producing a lactic acid bacterium in which the activity to induce IL-10 production remains and the activity to induce IL-12 production is almost lost by culturing.

  In the first aspect, the lactic acid bacteria are preferably Lactobacillus pentosus YM2-2 strain (Accession No. FERM AP-21778).

  Furthermore, in the first aspect, it is preferable to add the alkaline agent so that the pH during culture is maintained in the range of 5.0 to 7.5.

  The second aspect of the present invention is a Lactobacillus pentosus, which has IL-10 production-inducing activity, and is a cell of lactic acid bacteria with almost no IL-12 production-inducing activity and / or a treated product thereof. And providing a composition for immunomodulation.

  In the second aspect, it is preferable to use, as an active ingredient, cells obtained from a culture of Lactobacillus pentosus YM2-2 strain (Accession No. FERM AP-21778) and / or a treated product thereof.

  According to the method for producing lactic acid bacteria of the present invention, the activity to induce production of IL-12 having the function of causing an excessive immune response while the activity to induce production of IL-10 having the function of suppressing excessive immune response remains It is possible to produce lactic acid bacteria that have almost disappeared.

  In addition, according to the composition for immunomodulation of the present invention, while the activity to induce the production of IL-10 having the function of suppressing the excessive immune response remains, and the IL-12 having the function of causing the excessive immune response. Since the production induction activity is almost abolished, the immunosuppressive function by IL-10 can be exerted without causing an excessive immune response by IL-12.

FIG. 1 is a diagram showing IL-10 production inducing activity. FIG. 2 shows the IL-12 production-inducing activity.

  The method for producing lactic acid bacteria according to the present invention belongs to Lactobacillus pentosus, and the lactic acid bacteria having IL-10 production-inducing activity and IL-12 production-inducing activity are added while an alkaline agent is added so as to suppress the pH decrease with culture. By culturing, it is characterized in that the IL-10 production-inducing activity remains and produces a lactic acid bacterium in which the IL-12 production-inducing activity has almost disappeared.

  The lactic acid bacteria used in the present invention are lactic acid bacteria belonging to Lactobacillus pentosus, which have an activity of inducing production of IL-10 and IL-12.

  The lactic acid bacteria as described above are cultured using, for example, viable bacteria or killed bacteria of lactic acid bacteria obtained by adding the alkaline agent so as to suppress the decrease in pH accompanying the culture, for example, the lactic acid bacteria belonging to Lactobacillus pentosus. An IL-10 and IL-12 production induction test can be performed to obtain an IL-10 production-inducing activity that remains and detects almost no loss of the IL-12 production-inducing activity.

  As a lactic acid bacterium suitable for the present invention, for example, Lactobacillus pentosus strain YM2-2 (Accession No. FERM AP-21778) can be used. Lactobacillus pentosus YM2-2 is a lactic acid bacterium isolated from Awa later tea, which has an adjuvant effect when used in combination with a vaccine, and even when administered alone, protects rotavirus infection to the same extent as the vaccine. It is known that (patent 5324283).

  In the method for producing a lactic acid bacterium of the present invention, the culture is carried out while adding an alkaline agent to the medium to adjust the pH so as to suppress the decrease in pH due to the metabolite (lactic acid etc.) of the lactic acid bacterium accompanying the culture. Culture).

  As an alkali agent to be added, for example, an aqueous solution of sodium hydroxide, potassium hydroxide, calcium hydroxide or the like, ammonia or the like can be used.

  The pH in culture is preferably adjusted and maintained at pH 5.0 to 7.5, more preferably pH 6.2 to 6.7. Although pH adjustment may be performed manually, it is simple and accurate if a pH automatic controller (pH stat) or the like is used.

  The medium is not particularly limited as long as it is suitable for the growth of lactic acid bacteria. As a culture medium suitable for growth of lactic acid bacteria, there may be mentioned a nutrient-rich liquid medium containing yeast extract, peptone, meat extract and the like. Commercially available media include "MRS bouillon MERCK" (trade name, Chemicals), "Difco Lactobacilli MRS Broth" (trade name, Nippon Becton, Ditkinson Co., Ltd.), etc. These media may be used. In addition, there is no particular limitation in using a desired medium composition as appropriate, such as when a special medium composition is required depending on the type of lactic acid bacteria.

If the specific example of the said neutralization culture is mentioned, pH 5.0-7.5, 28-35 degreeC in the culture medium of Lactobacillus pentosus "Difco Lactobacilli MRS Broth" (brand name, Nippon Becton Ditzkinson Co., Ltd.) The initial cell concentration is 1 × 10 ⁶ to 1 × 10 ⁷ cfu / mL, and the final cell concentration is 5 × 10 ^{9 to} 5 × 10 ¹⁰ cfu / mL. It can be grown. Alternatively, when the culture medium is maintained at 30 to 33 ° C. and maintained at pH 5.0 to 7.5 for 18 to 24 hours, the initial cell concentration is 1 × 10 ⁶ to 1 × 10 ⁷ cfu / mL and the final concentration is The cell concentration can be increased to 5 × 10 ^{9 to} 5 × 10 ¹⁰ cfu / mL.

  By performing neutralization culture in this manner, although the reason is not clear, it is possible to produce a lactic acid bacterium in which the IL-10 production-inducing activity remains and the IL-12 production-inducing activity has almost disappeared.

  Here, that the IL-10 production-inducing activity remains means that the IL-10 production-inducing activity can be sufficiently detected, for example, in the measurement method by cell culture and ELISA as shown in the examples described later. Means The sufficiently detectable amount is, for example, preferably 15% of the activity of the lactic acid bacteria subjected to neutralization culture when the IL-10 production-inducing activity of the lactic acid bacteria subjected to static culture (cultured without pH adjustment) is 100%. The above means, more preferably 20% or more, and most preferably 25% or more. If the IL-10 production-inducing activity is less than 15%, the IL-10 production-inducing effect is not sufficiently obtained, and the effect of the immunomodulation tends to be poor.

  In addition, an amount at which almost no IL-12 production-inducing activity is observed in a cell culture and measurement method by ELISA as shown in the examples described later, for example, that the IL-12 production-inducing activity is almost completely abolished Means to be. The amount hardly recognized is, for example, when the IL-12 production induction activity of the statically cultured lactic acid bacteria is 100%, the activity of the neutralized lactic acid bacteria is preferably 15% or less, more preferably 10% In the following, most preferably, it is 5% or less. If the IL-12 production inducing activity exceeds 15%, it may cause an excessive immune response, and the effect of immunomodulation tends to be reduced.

  In addition, the present invention is an immunity comprising, as an active ingredient, bacteria of lactic acid bacteria belonging to Lactobacillus pentosus, having an activity to induce IL-10 production and having almost no activity to induce IL-12 production and / or a treated product thereof. A control composition is included.

  The cells and / or the processed product thereof for use in the composition for immunomodulation of the present invention may be a viable cell, a dead cell or a processed product of the above-mentioned lactic acid bacteria. As the treated cells, it is possible to use dry matter, freeze-dried matter, sonicated matter, treated surfactant, treated organic solvent, treated solvent, treated with lytic enzyme, immobilized cells, or immobilized cells, as the treated cells. In addition to the purified enzyme, etc., the concentrate of the culture solution of the strain, the dried product, the frozen product, the refrigerated product, the freeze-dried product, the sonicated product, the surfactant-treated product, the organic solvent-treated product, the solvent extract, the lysis Enzyme-treated products and the like can be mentioned.

  The dead cells include those obtained by sterilizing lactic acid bacteria that have undergone neutralization culture. The method of sterilization is not particularly limited, and the medium is separated by filtration, removed by centrifugation, sedimentation or the like after culture, and collected, and suspended with water, buffer solution or the like to prepare a concentrate of lactic acid bacteria as usual. The method of heat-sterilizing this etc. is mentioned. Alternatively, the culture solution after culture is subjected to heat sterilization treatment, and thereafter the culture medium is removed by filtration, centrifugation, sedimentation, etc. to collect the bacteria, and further, after culture, part of the culture medium is filtered off, centrifuged, sedimentation etc. After preparing a concentrated solution which has been removed and concentrated 2 to 10 times, it may be subjected to heat sterilization treatment, and then the remaining medium may be removed by filtration, centrifugation, sedimentation or the like to collect bacteria. The heat sterilization is preferably performed at 80 ° C. or higher, and more preferably at 80 to 100 ° C. for 5 to 20 minutes.

  According to the composition for immunomodulation of the present invention, it is possible to modulate the systemic immune system by exerting an immunosuppressive function by IL-10 without causing an excessive immune response by IL-12. Here, "regulating the immune system" means to normalize the immune system by acting on the innate immune system and the acquired immune system against any diseases caused by abnormal hyperfunction or depression of the immune system.

Specific diseases expected to be improved by the composition for immunomodulation of the present invention include, for example, arthritis, cerebrospinal meningitis, type I diabetes, Crohn's disease, ulcerative colitis, joints Examples include autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis vulgaris, chronic gastritis, autoimmune hepatitis, Graves' disease, and allergic diseases such as cedar pollinosis and atopic dermatitis.

  The composition for immunomodulation of the present invention may be in the form of a composition for food. That is, the cells of lactic acid bacteria and / or their processed products may be used as they are or in combination with other food materials to form a composition for food. Examples of food raw materials to be combined with the cells and / or processed products thereof include various sugars, emulsifiers, sweeteners, acidulants, fruit juices, flavors and the like. More specifically, sugars such as glucose, sucrose, fructose and honey, sugar alcohols such as sorbitol, xylitol, erythritol, lactitol and palatinit, and emulsifiers such as sucrose fatty acid esters, glycerin sugar fatty acid esters and lecithin. Besides these, various vitamins such as vitamin A, vitamin Bs, vitamin C and vitamin E, herb extracts, cereal ingredients, vegetable ingredients, milk ingredients and the like can be mentioned.

  In addition, the form of the food includes, but is not limited to, cookies, rice crackers, jellies, yogurts, confections such as yogurt, steamed buns, soft drinks, nutritional drinks, soups and the like. In addition, it may be in the form of health food, supplement, food for specified health, functional indication food, etc. provided for the purpose of health, health maintenance / promotion, etc. in a more positive sense than ordinary food.

  The composition for immunomodulation of the present invention may be in the form of a pharmaceutical composition. That is, the cells and / or the treated product thereof may be used as it is or in combination with other pharmaceutical raw materials to form a pharmaceutical composition. There is no particular limitation on the other pharmaceutical raw materials to be combined with the cells and / or the treated products thereof, and if necessary, pharmaceutically acceptable base materials and carriers are added, for example, tablets according to known formulation methods. In the form of granules, capsules, pills, powders, solutions, powders, jellies, chewing agents and the like, these can be used as an oral preparation. Moreover, it can be made into an ointment, a cream, a gel, a lotion, etc., and this can be utilized as a skin external preparation.

  Moreover, as a dosage form of a medicine, in order to make it act from the inside of a body, you may ingest orally, or you may apply and use it on skin. Moreover, it may be inhaled and applied to the respiratory system, and the administration form is not particularly limited. The dose may also be appropriately set depending on the health condition and age of the subject, and to what extent the immune modulation effect is required. Typically, the intake of the above-mentioned cells and / or their processed products in terms of dry matter is preferably 1 mg to 1,000 mg / day / kg, and 10 mg to 200 mg / day / kg Is more preferred. In addition, a medicine is the meaning including not only human but also medicine for animals.

  The composition for immunomodulation of the present invention may be in the form of a composition for animal feed. That is, the cells and / or their processed products may be used as they are or in combination with other animal feed materials to form an animal feed composition. The composition for immunomodulation of the present invention may be used, for example, as feeds for livestock, race horses, animals for appreciation, etc .; feeds for animals such as pet food, etc.

  In the composition for immunomodulation of the present invention, when the content of the cells and / or the processed product thereof is in various forms, it is appropriately determined in consideration of the relationship between the amount used and the effective dose. It should be determined. Typically, it is preferable to contain 0.1 to 100% by mass, preferably 1 to 50% by mass, in terms of dry matter, of the cells and / or the treated product thereof, and 10 to 30%. It is even more preferable to contain%.

  EXAMPLES The present invention will be specifically described by way of the following examples, but these examples do not limit the scope of the present invention.

[Culturing of lactic acid bacteria]
Lactobacillus pentosus YM2-2 strain (Accession No. FERM AP-2717) (hereinafter referred to as "YM2-2 bacteria") was used as the lactic acid bacteria. The medium is Difco Lactobacilli MRS Broth (trade name, Nippon Becton-Ditzkinson Co., Ltd.), and the final cell concentration is approximately 5 × 10 ^{9 to} 5 × 10 ¹⁰ cfu / mL at 35 ° C. Culture was performed. When adjusting the pH of the medium, the culture was performed while adjusting to pH 6.3 ± 0.1 with sodium hydroxide using a pH automatic controller (pH stat).

[Process of lactic acid bacteria]
The treatment after culture was carried out as follows except where indicated.

  After 90 mL of the culture broth was sterilized at 80 ° C. for 10 minutes in an autoclave, the cells were collected by centrifugation and suspended in about 20 mL of phosphate buffer so that the cell concentration became 1 to 4%. This was subjected to a Teflon (registered trademark) homogenizer to avoid aggregation of bacterial cells and to disperse as much as possible. After sterilizing the cell suspension thus obtained at 121 ° C. for 15 minutes, ultrasonication is performed for 30 minutes to prevent aggregation of the cells and separately measure the solid content of the cell suspension. The concentration was adjusted to a predetermined concentration based on the value, and the following production induction test was performed.

[IL-10 and IL-12 production induction test]
In vitro culture system of mouse spleen cells was used for IL-10 and IL-12 production induction test. Specifically, spleen cells are collected from 8-week-old BALB / c mice and suspended in RPMI 1640 medium containing 10% FBS, 50 μM 2-mercaptoethanol, 100 U / mL penicillin, 100 μg / mL streptomycin according to a conventional method. A solution (2.5 × 10 ⁶ cells / mL) was prepared. A cell / cell mixture is prepared by adding YM2-2 bacteria treated with the above or OK432 to a final concentration of 1 μg / mL or 10 μg / mL in terms of dry matter, to prepare a 96-well plate. 0.2 mL each was poured into each well. The culture supernatant is cultured under the conditions of 37 ° C. and 5% CO ₂ for 3 days in the case of IL-10, and 1 day in the case of IL-12, and the culture supernatant after culture is collected. The amounts of -10 and IL-12 were measured. The amount of IL-10 was measured by ELISA using kit "DuoSet IL-10" (trade name, R & D company). For measurement of the amount of IL-12, "capture Ab" as a primary antibody, "detection Ab" as a secondary antibody, "HRP-Avidin" (each trade name, BioLegend Inc.) as a detection reagent, "TMB as a chromogenic substrate (3,3 ', 5, 5' tetramethylbenzidine) "(trade name, Sigma. Life Scienc) was used to measure by sandwich ELISA. The results were determined as the average of 6 wells of the immunoplate.

[result]
When using YM2-2 bacteria and OK432 (1 μg / mL, 10 μg / mL) and culturing while adjusting the pH while adding an alkaline agent (sodium hydroxide) to the medium (hereinafter referred to as "neutralization culture") In the case of culture without pH adjustment (hereinafter referred to as "pH unadjusted culture"), the obtained IL-10 production-inducing activity (Fig. 1) and IL-12 production-inducing activity (Fig. 2) It was measured.

  As shown in FIG. 1, the IL-10 production-inducing activity of 1 μg / mL of bacterial cells obtained by culturing without adjustment of pH of YM2-2 bacteria was 461 pg / mL in terms of IL-10 production. On the other hand, neutralization culture in the same medium resulted in 130 pg / mL. That is, when the IL-10 production-inducing activity of 1 μg / mL of cells obtained by pH unadjusted culture is 100%, the activity of the cells obtained by neutralization culture was 28%.

  Moreover, the IL-10 production induction activity of 10 micrograms / mL of the microbial cells obtained by culture | cultivating unadjusted pH of YM2-2 bacteria was 627 pg / mL in IL-10 production amount. On the other hand, when the neutralization culture was performed in the same medium, it was 259 pg / mL. That is, when the IL-10 production-inducing activity of 10 μg / mL of cells obtained by stationary culture was 100%, the activity of the cells obtained by neutralization culture was 41%.

  As shown in FIG. 2, the IL-12 production-inducing activity of 1 μg / mL of the bacterial cells obtained by culture without adjustment of pH of YM2-2 bacteria was 646 pg / mL in terms of IL-12 production. On the other hand, when the neutralization culture was performed in the same medium, it was -57 pg / mL. The reason why the value became negative in this way is that the detection accuracy was lowered at a level at which almost no IL-12 production-inducing activity was observed, and it is presumed that the actual concentration is close to 0 pg / mL.

  In addition, the IL-12 production inducing activity of 10 μg / mL of the bacterial cells obtained by pH unadjusted culture of YM2-2 bacteria was 308 pg / mL as IL-12 production amount. On the other hand, when the neutralization culture was performed in the same medium, it was 12 pg / mL. That is, when the IL-12 production-inducing activity of 10 μg / mL of cells obtained by pH unadjusted culture is 100%, the activity of the cells obtained by neutralization culture was 3.9%.

  Thus, by carrying out the neutralization culture of the Lactobacillus pentosus YM2-2 strain, the IL-10 production induction activity remained, and the lactic acid bacteria in which the IL-12 production induction activity abolished were able to be manufactured.

As a lactic acid bacterium suitable for the present invention, for example, Lactobacillus pentosus strain YM2-2 (Lactobacillus pentosus strain YM2-2) (Accession number: FERM AP-21778, Depositary organization: National Institute of Advanced Industrial Science and Technology, International Patent Organism Depositary) Date of deposit: March 4, 2009) can be used. Lactobacillus pentosus YM2-2 is a lactic acid bacterium isolated from Awa later tea, which has an adjuvant effect when used in combination with a vaccine, and even when administered alone, protects rotavirus infection to the same extent as the vaccine. It is known that (patent 5324283).

In the first embodiment, the lactic acid bacteria is preferably a Lactobacillus pentosus YM2-2 strain (consignment number FERM P -21778).

The second aspect is preferably set to a Lactobacillus pentosus YM2-2 strain (consignment number FERM P -21,778) obtained cells and / or active ingredient treated product thereof from a culture of.

Suitable lactic acid bacteria in the present invention, for example, Lactobacillus pentosus YM2-2 strains (Lactobacillus pentosus strain YM2-2) (consignment number: FERM P -21778, depositary institution: National Institute of Advanced Industrial Science and Technology, International Patent Organism Depositary A center (AIST, 1-1-1 Central 6th East, Tsukuba City, Ibaraki Prefecture, Japan, deposit date: March 4, 2009) can be used. Lactobacillus pentosus YM2-2 is a lactic acid bacterium isolated from Awa later tea, which has an adjuvant effect when used in combination with a vaccine, and even when administered alone, protects rotavirus infection to the same extent as the vaccine. It is known that (patent 5324283).

[Culturing of lactic acid bacteria]
Lactic acid bacteria, Lactobacillus pentosus YM2-2 strain (consignment number FERM P -21778) (hereinafter referred to. As "YM2-2 bacteria") was used. The medium is Difco Lactobacilli MRS Broth (trade name, Nippon Becton-Ditzkinson Co., Ltd.), and the final cell concentration is approximately 5 × 10 ^{9 to} 5 × 10 ¹⁰ cfu / mL at 35 ° C. Culture was performed. When adjusting the pH of the medium, the culture was performed while adjusting to pH 6.3 ± 0.1 with sodium hydroxide using a pH automatic controller (pH stat).

Claims (5)

  By culturing a lactic acid bacterium belonging to Lactobacillus pentosus and having an activity to induce IL-10 production and an activity to induce IL-12 production while adding an alkaline agent so as to suppress a decrease in pH accompanying the culture, to produce IL-10 A method for producing lactic acid bacteria, which comprises producing lactic acid bacteria in which induction activity remains and IL-12 production induction activity is almost lost.   The method for producing lactic acid bacteria according to claim 1, wherein the lactic acid bacteria are Lactobacillus pentosus YM2-2 strain (Accession No. FERM AP-2717).   The manufacturing method of the lactic acid bacteria of Claim 1 or 2 which adds the said alkali chemicals so that pH in culture | cultivation may be maintained in the range of 5.0-7.5.   A composition for immunomodulation comprising Lactobacillus pentosus, an IL-10 production-inducing activity, and / or a treated product of a lactic acid bacterium having almost no IL-12 production-inducing activity as an active ingredient.   5. The composition for immunomodulation according to claim 4, which comprises, as an active ingredient, cells obtained from a culture of Lactobacillus pentosus strain YM2-2 (Accession No. FERM AP-2717) and / or a treated product thereof.

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