JP6002452B2 - New yeast and medicine or food and drink containing the same - Google Patents

Description

  The present invention relates to a novel yeast, a medicine containing the same, and a food and drink.

  Allergy is an immune reaction that occurs excessively against a specific antigen, and the immune reaction is a biological defense reaction that works to eliminate foreign substances (antigens). Allergic reactions are largely classified from type I to type IV according to the developmental mechanism (Coombs classification). In type I allergy, IgE binds to mast cells and basophils, and antigens bind to these cells, whereby these cells release mediators such as histamine and serotonin. Various symptoms appear by the action of this mediator. Allergic rhinitis, bronchial asthma, hives etc. are included. Type II allergy is a reaction in which IgG binds to an autologous cell having an antigen, and a white blood cell that recognizes it destroys the cell. Type III allergy is a reaction in which an immune complex formed by an immune reaction injures surrounding tissues where it has flowed into the bloodstream. Type IV allergy is a reaction in which various cytokines such as factors that activate macrophages are released from sensitized T cells that have reacted with an antigen, causing damage to surrounding tissues.

  Synthetic drugs such as antihistamines, histamine release inhibitors from mast cells, and various cytokine inhibitors have been developed for these allergic diseases. However, since these drug products have many side effects, anti-allergic agents derived from natural products have attracted attention.

  As such a natural product-derived physiologically active ingredient, a yeast-derived component NBG (Patent Document 1), a method for producing an immunomodulator by removing the water-soluble fraction of yeast belonging to the genus Saccharomyces (Patent Document 2), A soybean fermented product by yeast or lactic acid bacteria (Patent Document 3) is known.

International Publication WO2003 / 039567 Pamphlet JP 2007-291006 A JP 2007-197333 A

However, the pharmacological action of these yeast-derived components and fermented soybeans is not sufficient, and further new materials and their use have been desired.
Accordingly, an object of the present invention is to provide a natural material useful for the prevention and treatment of various immune diseases by suppressing the production of IgE causing allergic symptoms or promoting the production of useful cytokines. is there.

  Therefore, the present inventors have isolated novel yeasts from various natural products existing in Kiso-machi and studied their pharmacological actions. As a result, seven yeasts belonging to the genus Saccharomyces have IL-12 production-promoting action, IFN -It has a gamma production promoting action and an IgE production inhibitory action, and based on the immunomodulating action, has been found to be useful as a pharmaceutical or food and drink for the prevention and treatment of various immune diseases, particularly various allergic diseases, and the present invention. Was completed.

That is, the present invention provides the following [1] to [4].
[1] Kiso yeast S02 (NITE P-1293) belonging to Saccharomyces cerevisiae, Kiso yeast S03 (NITE P-1294) belonging to Saccharomyces cerevisiae, Koji yeast P01 (NITE P-1290) belonging to Saccharomyces paradoxus, Saccharomyces Koji yeast P02 (NITE P-1291) belonging to Paradoxus, Koji yeast S01 (NITE P-1292) belonging to Saccharomyces paradoxus, Kiso yeast S04 (NITE P-1295) belonging to Saccharomyces paradoxus or Kiso yeast belonging to Saccharomyces paradoxus S05 (NITE P-1296).
[2] A medicine or food or drink containing the yeast according to [1].
[3] An immunomodulator comprising the yeast according to [1].
[4] An antiallergic agent comprising the yeast according to [1].

  By using the yeast of the present invention, it is possible to prevent or treat various immune diseases in which IL-12 or IFN-γ is involved or IgE is involved. The yeast of the present invention is naturally derived, and can be applied not only to pharmaceuticals but also to various foods and beverages.

The influence of koji yeast addition on IgE production of mouse spleen cells is shown. ** P <0.01, *** P <0.001. The influence of Kiso yeast addition on IL-12 production of mouse spleen cells is shown. * P <0.05, ** P <0.01, *** P <0.001. The influence of the addition of Koji yeast on IFN-γ production of mouse spleen cells is shown. * P <0.05.

  The yeast of the present invention (Kiso yeast) all belongs to the genus Saccharomyces, but S02 and S03 belong to Saccharomyces cerevisiae, and P01, P02, S01, S04 and S05 belong to Saccharomyces paradoxus. These koji yeasts are collected from flowers, fruits, leaves or soil collected from Kiso Town, Nagano Prefecture.

  To collect koji yeast from flowers, fruits, leaves, or soil, for example, accumulation culture in a broth medium is performed, and a sample in which foaming is observed is anaerobically cultured in a medium supplemented with 2 to 5% ethanol, and foaming is further observed. The obtained sample can be cultured on an agar medium and colonies can be isolated.

  Identification of the obtained colonies can be confirmed to be of the genus Saccharomyces by a yeast-like fungus determination test (31 kinds of carbon source utilization tests by API ID 32C).

  The fact that these yeasts belong to Saccharomyces cerevisiae or Paradoxus was determined by gene analysis of the 26S rDNA D1 / D2 region, homology search with an international nucleotide sequence database, and simple molecular phylogenetic tree analysis.

  The seven yeasts obtained were: Kite yeast P01 as NITE P-1290, Kiso yeast P02 as NITE P-1291, Kiso yeast S01 as NITE P-1292, Kiso yeast S03 as NITE P-1293, Kiso yeast S04 as NITE P-1294 and Kiso yeast S05 were deposited as NITE P-1295 with the National Institute of Technology and Evaluation.

As shown in the examples described later, the yeast of the present invention has an excellent IgE production inhibitory action, and also has an IL-12 production promoting action and an IFN-γ production promoting action.
IL-12 is an IFN-γ inducer, and is known to activate NK cells and NKT cells and induce IFN-γ production. In addition, naive helper T cells are induced to differentiate into type I helper T cells (Th1) cells. IFN-γ is mainly produced from CD4-positive type I helper T cells (Th1) cells, CD8-positive T cells, NK cells, and NKT cells. IFN-γ has an action of suppressing the production of IgE by suppressing type II helper T cells (Th2), and also has an action of activating macrophages, an action of improving production of nitric oxide by macrophages, and the like. Are known. Therefore, the yeast of the present invention is useful as an immunomodulator and is useful as a prophylactic and therapeutic agent for various immune diseases, particularly allergic diseases. Preferred allergic diseases to be considered here are type I allergies such as hay fever, allergic rhinitis, allergic conjunctivitis, allergic gastroenteritis, allergic diarrhea, bronchial asthma, hives, anaphylactic shock, atopic dermatitis, etc. Can be mentioned.

  When the yeast of the present invention is used as an immunomodulator, either oral administration or parenteral administration can be used, but oral administration is desirable. Regarding administration, yeast cells as an active ingredient can be mixed with a solid or liquid nontoxic pharmaceutical carrier suitable for the administration method and administered in the form of a conventional pharmaceutical preparation.

  There is no strict limitation on the dosage when using koji yeast which is an active ingredient of the immunomodulator of the present invention. Since the effects obtained by various use modes such as the subject and applicable diseases are different, it is desirable to appropriately set the dosage, but for koji yeast, the preferred dosage is 1 mg to 10 g per day in terms of cell weight, More preferably, it is 10 mg to 1 g.

  Examples of such preparations include solid agents such as tablets, granules, powders and capsules, solutions such as solutions, suspensions and emulsions, and freeze-dried agents. These preparations can be prepared by conventional means on the preparation. Examples of the non-toxic pharmaceutical carrier include starch, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, albumin, water, and physiological saline. It is done. In addition, conventional additives such as stabilizers, wetting agents, emulsifiers, binders, isotonic agents, excipients and the like can be appropriately added as necessary.

  In addition, the yeast and immunomodulator of the present invention can be used not only as a pharmaceutical preparation as described above but also as a food or drink. In this case, the yeast of the present invention may be contained in the food or drink as it is or with various nutritional components added. This food / beverage product can be used as a health food or food material useful for various immune diseases, and these food / beverage products or their containers may be labeled as having the above effects. Specifically, when the yeast of the present invention is blended in a food or drink, an additive that can be used as a food or drink is appropriately used, and a form suitable for food using conventional means, for example, granular, granular, tablet, It may be formed into capsules, pastes, etc. and added to various foods such as processed meat products such as ham and sausage, processed fish products such as kamaboko and chikuwa, bread, confectionery, butter, powdered milk, fermented food and drink Or added to beverages such as water, fruit juice, milk, soft drinks and tea drinks. The food and drink includes animal feed.

  Hereinafter, the content of the present invention will be described in more detail with reference to examples, but the present invention is not limited by these.

Example 1
〔Method〕
(1) As a yeast separation source, environmental resources including flowers, fruits, leaves and soil collected from Kiso Town, Nagano Prefecture were used as samples.
(2) A sample for yeast separation was saccharified with a high-temperature saccharification treatment by adding a 4-fold volume of distilled water to dried rice bran at 56 ° C. for 6 to 7 hours, and centrifuging (3 2,000 × rpm, 10 minutes) and 2% lactic acid, 0.2% sodium propionate, 0.01% chloramphenicol added to the supernatant and sterilized by autoclave). Aerobic culture for about a week was performed.
(3) YPS medium (2% sucrose, 1% dry yeast extract, 2% peptone, 0.2% sodium propionate) to which 2-5% ethanol was further added at 29 ° C. for the sample in which foaming was observed And anaerobic culture in 0.01% chloramphenicol, pH 5.8). Further, for samples in which foaming was observed, the culture solution was added to YPD medium (2% D-glucose, 1% dry yeast extract, 2% peptone, 0.2% sodium propionate, 0.01% chloramphenicol, Colonies were isolated by seeding on an agar medium supplemented with 1.5% agar at pH 5.8).
(4) About the isolated yeast colony, Kultzman et al. (2011) Yeast extract-malt extract agar (YM) on agar plate at 25 ° C. under aerobic culture, and on day 3 of culture, Morphological observations were made of the raised state, surface shape, gloss and properties, and color tone.
(5) With respect to the vegetative cells of the isolated yeast, the vegetative cells on the third day of culture were observed on a YM agar plate medium under an aerobic culture at 25 ° C., and the shape and budding were confirmed. In addition, the presence or absence of ascospores in vegetative cells after 3 weeks of culture on a YM agar plate medium at 25 ° C. was confirmed.

(6) The carbon source assimilation ability of yeast was determined using API ID 32C yeast-like fungus identification kit (manufactured by Sysmex Biomelieu), and 31 types of carbon sources (galactose, cycloheximide, sucrose, N-acetyl-glucosamine, lactic acid, L-arabinose, D-cellobiose, raffinose, D-maltose, trehalose, 2-keto-calcium gluconate, α-methyl-α-D-glucoside, D-mannitol, lactose, inositol, D-sorbitol, D-xylose, 48 hours for D-ribose, glycerol, L-rhamnose, palatinose, erythritol, D-melibiose, sodium glucuronate, D-meletitol, potassium gluconate, levulinic acid, glucose, L-sorbose, D-glucosamine hydrochloride, esculin) Later assimilation I saw over emissions. Bacterial species determination based on the results of the assimilation pattern obtained was input to the Apive ID 32C V3.0 database access site (https://apiweb.biomieux.com/servlet/Authenticate?action=prepalogin) .

(7) Identification of yeast strains is performed by analyzing the gene sequence of the 26S rDNA D1 / D2 region and homologous to Apollon DB-FU5.0 (Techno Suruga) and the international base sequence database (Genbank / DDBJ / EMBL). The search and simple molecular phylogenetic tree analysis were performed.

〔result〕
(1) When the koji yeast P01 was cultured on a YM agar medium for 3 days, it formed a cushion-type white to cream-colored colony having a flat shape at the periphery at the entire edge. In addition, the vegetative cells in the third week of culturing showed a sub-spherical to wide-elliptical shape, proliferated by multipolar budding, and formation of 2 to 4 sub-spherical ascospores in the ascosm. It was. This species has the property of assimilating galactose, sucrose, raffinose, α-methyl-α-D-glucoside, palatinose and glucose in the API ID32C carbon source assimilation test, and belongs to Saccharomyces paradoxus as a result of gene analysis It became clear that it was a strain.

(2) When the koji yeast P02 was cultured on a YM agar medium for 3 days, it formed a cushion-type white to cream-colored colony having a flat shape on the periphery at the entire edge. In addition, the vegetative cells in the third week of culturing showed a sub-spherical to wide-elliptical shape, proliferated by multipolar budding, and formation of 2 to 4 sub-spherical ascospores in the ascosm. It was. This species has the property to assimilate galactose, sucrose, raffinose, maltose, α-methyl-α-D-glucoside, palatinose, glucose in the API ID32C carbon source assimilation test. As a result of gene analysis, Saccharomyces paradoxus It became clear that it was a strain belonging to.

(3) When the koji yeast S01 was cultured on a YM agar medium for 3 days, it formed a cushion-type white to cream-colored colony having a flat shape at the entire periphery and the periphery. In addition, the vegetative cells in the third week of culturing showed a sub-spherical to wide-elliptical shape, proliferated by multipolar budding, and formation of 2 to 4 sub-spherical ascospores in the ascosm. It was. This species has the property of assimilating galactose, sucrose, raffinose, α-methyl-α-D-glucoside, palatinose and glucose in the API ID32C carbon source assimilation test, and belongs to Saccharomyces paradoxus as a result of gene analysis It became clear that it was a strain.

(4) When the koji yeast S02 was cultured on a YM agar medium for 3 days, it formed a cushion-type white to cream-colored colony having a flat shape on the periphery at the entire edge. In addition, the vegetative cells in the third week of culturing showed a sub-spherical to wide-elliptical shape, proliferated by multipolar budding, and formation of 2 to 4 sub-spherical ascospores in the ascosm. It was. This species has the property of assimilating galactose, sucrose, raffinose, α-methyl-α-D-glucoside, palatinose and glucose in the API ID32C carbon source utilization test, and belongs to Saccharomyces cerevisiae as a result of gene analysis It became clear that it was a strain.
(5) When the koji yeast S03 was cultured on a YM agar medium for 3 days, it formed a cushion-type white to cream-colored colony having a flat shape at the entire periphery and the periphery. In addition, the vegetative cells in the third week of culturing showed a sub-spherical to wide-elliptical shape, proliferated by multipolar budding, and formation of 2 to 4 sub-spherical ascospores in the ascosm. It was. This species has the property of assimilating galactose, sucrose, raffinose, α-methyl-α-D-glucoside, palatinose and glucose in the API ID32C carbon source utilization test, and belongs to Saccharomyces cerevisiae as a result of gene analysis It became clear that it was a strain.

(6) When the koji yeast S04 was cultured on a YM agar medium for 3 days, it formed a cushion-type white to cream-colored colony having a flat shape at the entire periphery. In addition, the vegetative cells in the third week of culturing showed a sub-spherical to wide-elliptical shape, proliferated by multipolar budding, and formation of 2 to 4 sub-spherical ascospores in the ascosm. It was. This species has the property of assimilating galactose, sucrose, lactic acid, raffinose, maltose, α-methyl-α-D-glucoside, palatinose, α-meretitol, glucose in the API ID32C carbon source assimilation test, Analysis revealed that the strain belongs to Saccharomyces paradoxus.

(7) When Kiso yeast S05 was cultured on a YM agar medium for 3 days, it formed a cushion-type white to cream-colored colony having a flat shape at the entire periphery. In addition, the vegetative cells in the third week of culturing showed a sub-spherical to wide-elliptical shape, proliferated by multipolar budding, and formation of 2 to 4 sub-spherical ascospores in the ascosm. It was. This species has the property of assimilating galactose, sucrose, raffinose, maltose, α-methyl-α-D-glucoside, palatinose, α-meretitol, glucose in the API ID32C carbon source assimilation test. As a result, it was revealed that the strain belongs to Saccharomyces paradoxus.

Example 2
〔Method〕
(1) The isolated strain was cultured at 29 ° C. using YPD medium. After confirming the growth, the culture solution was centrifuged (3000 × rpm, 10 minutes) to obtain a precipitate. Centrifugal washing was performed twice with ultrapure water in order to remove medium components from the resulting precipitate. This precipitate was stored at −80 ° C. and freeze-dried.

(2) The spleen was aseptically removed from BALB / c female mice (Japan SLC) euthanized by cervical dislocation, and then spleen cells were taken out in RPMI 1640 medium (manufactured by Nissui Pharmaceutical). After centrifugation at 2000 × rpm for 10 minutes, the suspension was suspended in erythrocyte hemolysis buffer (17 mM Tris-HCl, 0.144 M ammonium chloride, pH 7.2). After 5 minutes, RPMI 1640 medium was added, centrifuged at 2000 × rpm for 10 minutes to remove the supernatant, and the cells were removed with RPMI 1640 medium supplemented with 10% inactivated fetal bovine serum (Hyclone). It prepared to x10 < ⁶ > cells / ml. Using a 96-well culture microplate (BD falcon), 100 μl / well of the spleen cell suspension 100 μl / well (final concentration 10 μg / ml (when measuring the amount of cytokine)) and 100 μg / ml (when measuring the amount of antibody) And the cells were cultured under conditions of 37 ° C. and 5% CO _2. For the cytokines and antibodies for measurement, the culture supernatants on the 3rd and 7th days of culture were collected and subjected to sandwich ELISA.

(3) The amount of IgE in the spleen cell culture supernatant was measured by sandwich ELISA using Goat anti-mouse IgE (Bethyl) as a solid layer antibody and Goat anti-Mouse IgE HRP conjugated (Bethyl) as a detection antibody. It went by. Each primary antibody was dissolved in 0.1 M carbonate buffer (pH 10.0), added to 96-well Nunc Immuno Plate MaxiSorp (Thermo Fisher Scientific) at 100 μl / well and allowed to stand at 37 ° C. for 90 minutes. did. Thereafter, the plate was washed 3 times with T-PBS, a carbonate buffer solution added with 1% skim milk was added in an amount of 300 μl / well, and the mixture was allowed to stand at 4 ° C. overnight. Thereafter, the plate was washed 5 times with T-PBS, antidinitrophenyl (DNP) mouse IgE antibody (Sigma) as a standard and serially diluted with T-PBS was added at 50 μl / well at 60 ° C. at 60 ° C. Reacted for 1 minute. Thereafter, the plate was washed 3 times with T-PBS, and an antibody for detection was added at 100 μl / well in the dark and allowed to react at 37 ° C. for 30 minutes. After the reaction, the plate was washed 5 times with T-PBS, and developed with TMB Microwell Peroxidase Substrate System (manufactured by Kirkegaard & Perry Laboratories) in the dark. After the color development, 100 μl of phosphoric acid was added to stop the reaction, and the absorbance at 450 nm was measured using Model 550 (manufactured by Bio-Rad Laboratories).

(4) IL-12 in the spleen cell culture supernatant was measured using Purified Rat Anti-Mouse IL-12 p40 / p70 (manufactured by BD Pharmingen) as a solid layer antibody and Biotin Rat Anti-Mouse IL as a detection antibody. -12 p40 / p70 (BD Pharmingen) was performed by sandwich ELISA method combined with Streptavidin HRP (BD Pharmingen). In addition, for the measurement of IFN-γ, a sandwich ELISA in which Purified Rat Anti-Mouse IFN-γ (BD Pharmingen) was used as a solid-phase antibody and Biotin Anti-Mouse IFN-γ (BD Pharmingen) was combined with Streptavidin HRP as a detection antibody. Done by law. Each primary antibody was dissolved in 0.1 M carbonate buffer (pH 10.0), added to 96-well Nunc Immuno Plate MaxiSorp at 100 μl / well, and allowed to stand at 37 ° C. for 90 minutes. Thereafter, the plate was washed with 0.05% Tween 20-added PBS (T-PBS) three times, carbonate buffer to which 1% skim milk was added was added in an amount of 300 μl / well and allowed to stand at 4 ° C. overnight. Thereafter, the sample was washed 5 times with T-PBS. Recombinant Murine IL-12 (manufactured by PeproTech) was used as each sample solution and standard as IL-12, and Recombinant Murine IFN-γ (PeproTech) was used as TFN for IFN-γ. What was diluted with PBS was added at 50 μl / well and reacted at 37 ° C. for 60 minutes. Then, it wash | cleaned 3 times by T-PBS, the secondary antibody was added at 100 microliters / well under light-shielding, and it was made to react at 37 degreeC for 30 minutes. After the reaction, the plate was washed 5 times with T-PBS, Streptavidin HRP was added at 100 μl / well, and the mixture was reacted at 37 ° C. for 30 minutes. After the reaction, it was washed 5 times with T-PBS, and developed with TMB Microwell Peroxidase Substrate System under light shielding. After color development, 100 μl of phosphoric acid was added to stop the reaction, and the absorbance at 450 nm was measured using a microplate reader Model 550.

〔result〕
(1) Regarding the antibody production amount, a significant decrease in the IgE production amount at the time of addition was confirmed for all of the koji yeasts P01 and P02 and the koji yeasts S01, S02, S03, S04, and S05 (FIG. 1). This means that the degranulation reaction induced by the interaction between IgE and mast cells is suppressed by the action of the yeast of the present invention.

(2) Regarding cytokine production, significant increases in IL-12 production at the time of addition were confirmed for all of the koji yeasts P01 and P02 and the koji yeasts S01, S02, S03, S04, and S05 (FIG. 2). Moreover, about the koji yeast S03, the significant increase in the IFN-gamma production amount at the time of addition was confirmed (FIG. 3).

  It is known that helper T cell (Th) type 1 and Th2 type immune responses form a balanced immune response in the living body by maintaining an antagonistic state in which each other suppresses the partner. IL-12 or IFN-γ that induces an immune response suppresses a Th2-type immune response and induces a biological immune response to the Th1-type. One of the causes of the increase in immediate type (especially type I) allergy in developed countries in recent years is related to the production of a large amount of IgE antibody in a significant immune response of the Th2 type immune response. ing. The yeast of the present invention is expected to exert an antiallergic effect by suppressing Th1 type immune responses including IgE antibody production induced by Th1 type cytokines.

Claims (7)

  Koji yeast S02 (NITE P-1293) belonging to Saccharomyces cerevisiae, Kiso yeast S03 (NITE P-1294) belonging to Saccharomyces cerevisiae, Kiso yeast P01 (NITE P-1290) belonging to Saccharomyces paradoxus, Saccharomyces paradoxus Kiso yeast P02 (NITE P-1291), Kiso yeast S01 (NITE P-1292) belonging to Saccharomyces paradoxus, Kiso yeast S04 (NITE P-1295) belonging to Saccharomyces paradoxus or Kiso yeast S05 (NITE belonging to Saccharomyces paradoxus) P-1296). Koji yeast S02 (NITE P-1293) belonging to Saccharomyces cerevisiae, Kiso yeast S03 (NITE P-1294) belonging to Saccharomyces cerevisiae, Kiso yeast P01 (NITE P-1290) belonging to Saccharomyces paradoxus, Saccharomyces paradoxus Kiso yeast P02 (NITE P-1291), Kiso yeast S01 (NITE P-1292) belonging to Saccharomyces paradoxus, Kiso yeast S04 (NITE P-1295) belonging to Saccharomyces paradoxus or Kiso yeast S05 (NITE belonging to Saccharomyces paradoxus) An IgE production inhibitor comprising P-1296) as an active ingredient . Koji yeast S02 (NITE P-1293) belonging to Saccharomyces cerevisiae, Kiso yeast S03 (NITE P-1294) belonging to Saccharomyces cerevisiae, Kiso yeast P01 (NITE P-1290) belonging to Saccharomyces paradoxus, Saccharomyces paradoxus Kiso yeast P02 (NITE P-1291), Kiso yeast S01 (NITE P-1292) belonging to Saccharomyces paradoxus, Kiso yeast S04 (NITE P-1295) belonging to Saccharomyces paradoxus or Kiso yeast S05 (NITE belonging to Saccharomyces paradoxus) A food and drink composition for suppressing IgE production comprising P-1296) as an active ingredient. Koji yeast S02 (NITE P-1293) belonging to Saccharomyces cerevisiae, Kiso yeast S03 (NITE P-1294) belonging to Saccharomyces cerevisiae, Kiso yeast P01 (NITE P-1290) belonging to Saccharomyces paradoxus, Saccharomyces paradoxus Kiso yeast P02 (NITE P-1291), Kiso yeast S01 (NITE P-1292) belonging to Saccharomyces paradoxus, Kiso yeast S04 (NITE P-1295) belonging to Saccharomyces paradoxus or Kiso yeast S05 (NITE belonging to Saccharomyces paradoxus) An immunomodulator by suppressing IgE production comprising P-1296) as an active ingredient. Koji yeast S02 (NITE P-1293) belonging to Saccharomyces cerevisiae, Kiso yeast S03 (NITE P-1294) belonging to Saccharomyces cerevisiae, Kiso yeast P01 (NITE P-1290) belonging to Saccharomyces paradoxus, Saccharomyces paradoxus Kiso yeast P02 (NITE P-1291), Kiso yeast S01 (NITE P-1292) belonging to Saccharomyces paradoxus, Kiso yeast S04 (NITE P-1295) belonging to Saccharomyces paradoxus or Kiso yeast S05 (NITE belonging to Saccharomyces paradoxus) A food / beverage product composition for immunoregulation by suppressing IgE production comprising P-1296) as an active ingredient.   Koji yeast S02 (NITE P-1293) belonging to Saccharomyces cerevisiae, Kiso yeast S03 (NITE P-1294) belonging to Saccharomyces cerevisiae, Kiso yeast P01 (NITE P-1290) belonging to Saccharomyces paradoxus, Saccharomyces paradoxus Kiso yeast P02 (NITE P-1291), Kiso yeast S01 (NITE P-1292) belonging to Saccharomyces paradoxus, Kiso yeast S04 (NITE P-1295) belonging to Saccharomyces paradoxus or Kiso yeast S05 (NITE belonging to Saccharomyces paradoxus) An antiallergic agent by suppressing IgE production comprising P-1296) as an active ingredient.   Koji yeast S02 (NITE P-1293) belonging to Saccharomyces cerevisiae, Kiso yeast S03 (NITE P-1294) belonging to Saccharomyces cerevisiae, Kiso yeast P01 (NITE P-1290) belonging to Saccharomyces paradoxus, Saccharomyces paradoxus Kiso yeast P02 (NITE P-1291), Kiso yeast S01 (NITE P-1292) belonging to Saccharomyces paradoxus, Kiso yeast S04 (NITE P-1295) belonging to Saccharomyces paradoxus or Kiso yeast S05 (NITE belonging to Saccharomyces paradoxus) Anti-allergic food / beverage composition by suppressing IgE production comprising P-1296) as an active ingredient.