WO2018180728A1 - Composition for promoting expression of antiinflammatory gene - Google Patents

Abstract

The present invention addresses the problem of providing a composition for promoting the expression of an antiinflammatory gene and a composition for inhibiting the production of an inflammatory cytokine. A means for solving the problem is to use, as an active ingredient, a bacterium belonging to the genus Bifidobacterium, i.e., Bifidobacterium longum subsp. infantis LMG23728 and/or Bifidobacterium breve FERM BP-11175 or a culture thereof.

Description

Composition for promoting expression of inflammation control gene

The present invention relates to a composition for promoting the expression of inflammation control genes.

Intestinal health is important not only for one organ, the intestine, but also for general health. The intestinal tract tissue has a barrier function and is responsible for preventing pathogenic microorganisms from entering the living body, such as by mobilizing about 60% of immune cells in the human body.
When excessive inflammation occurs in the intestinal tissue, inflammatory cytokines (TNF-α, IL-1β, IL-6, etc.) produced by immune cells act on other organs to induce fever and C-reactive protein production. At the same time, the intestinal barrier function may be disrupted and spread to systemic chronic diseases.
For example, inflammatory bowel diseases such as ulcerative colitis and Crohn's disease are enteropathy of unknown cause and may be accompanied by complications other than the gastrointestinal tract, and are designated as designated intractable diseases.

As a treatment method for such inflammatory diseases including inflammatory bowel disease, for example, a human antibody drug such as an anti-IL-23 antibody drug (Non-patent Document 1) or a steroid drug therapy is known. .

In recent years, it has been clarified that the renin-angiotensin system, which is a biological system that controls blood pressure by regulating vasoconstriction and dilation, is involved in the control of inflammation in the intestinal tissue. (Non-Patent Document 1). Angiotensin converting enzyme 2 (ACE2), which is one of the enzymes that control the renin-angiotensin system, is an enzyme that converts AngII that induces vasoconstriction into Ang1-7 that antagonizes it, and suppresses inflammation. It is known to work (Non-Patent Document 2).
ACE2 is known to maintain the intestinal environment by controlling amino acid absorption in the small intestine and suppress inflammatory effects (Non-patent Document 3).

Also, Mucin1 (Muc-1) is known to suppress inflammatory signals via a wide range of TLR signals (Non-Patent Document 4).

By the way, the use of microorganisms that are beneficial to health maintenance such as Bifidobacterium is called “probiotics”, and many studies have been conducted. It has also been reported on the preventive or ameliorating action of inflammatory diseases caused by Bifidobacterium (Patent Documents 1 to 3).

JP 2012-158568 A International Publication No. 2007/122885 Pamphlet JP 2011-032170 A

As described above, therapeutic methods using human antibody drugs or steroid drugs are used for the treatment of serious inflammatory diseases including inflammatory bowel disease. However, these drug therapies are prone to side effects.
In particular, these problems are more serious for infants and children.
Therefore, an object of the present invention is to provide a composition for promoting the expression of an inflammation regulatory gene and a composition for suppressing inflammatory cytokine production that are safe and have high effects.
In particular, an object of the present invention is to provide a composition for promoting the expression of an inflammation regulatory gene and a composition for suppressing the production of inflammatory cytokines, which are excellent in safety for infants and children and have a high effect.

As a result of earnest research for active ingredients of a composition for promoting the expression of inflammatory regulatory genes or a composition for suppressing the production of inflammatory cytokines that are safe and highly effective, the present inventors have found that there are many in the body of infants The present invention was completed by finding that the culture obtained from a specific fungus among the strains to be observed has an effect of promoting the expression of inflammation control genes and the effect of suppressing the production of inflammatory cytokines.

The first invention for solving the above-mentioned problems is that Bifidobacterium infantis (Bifidobacterium longsp. Infantis) LMG23728 and / or Bifidobacterium breve (Bifidobacterium breve) FERM BP-11175 An agent for promoting expression of one or more inflammation control genes selected from the group consisting of ACE2, AgtR2, Mas-1, MKP-1, Muc-1, and IL-10, comprising a bacterium or a culture thereof as an active ingredient, or This is a composition for promoting expression. In the present specification, the terms “composition” and “agent” have the same meaning.

The present invention also relates to Bifidobacterium infantis (Bifidobacterium longum subsp. Infantis) LMG23728 and / or Bifidobacterium breve (Bifidobacterium breve) FERM BP-11175 Bifidobacterium or its Bifidobacterium genus Is an inflammatory cytokine production inhibitor of TNF-α and / or IL-23 or a composition for suppressing inflammatory cytokine production.

In a preferred form of the present invention, the active ingredient of the composition is the culture supernatant of the Bifidobacterium.

In a preferred form of the present invention, the composition is a pharmaceutical composition or a food or drink composition.

The composition of the present invention is preferably used for the prevention and / or improvement of one or more inflammatory diseases selected from inflammatory bowel disease, inflammatory joint disease, and inflammatory skin disease.

Moreover, the said bacteria which are an active ingredient of this invention, or its culture | cultivation are high safety | security also with respect to an infant or a child. Therefore, the expression promoter or expression promoting composition of the inflammation control gene of the present invention, or the inflammatory cytokine production inhibitor or the inflammatory cytokine production inhibitory composition is suitable for inflammatory diseases of infants or children. Can be used.
That is, the composition of the present invention is preferably used for prevention and / or improvement of inflammatory diseases in infants or children.

Further, the second invention for solving the above-mentioned problems is to promote the expression of one or more inflammation control genes selected from the group consisting of ACE2, AgtR2, Mas-1, MKP-1, Muc-1, and IL-10 Bifidobacterium infantis (Bifidobacterium longum subsp. Infantis) LMG23728 and / or Bifidobacterium breve FERM BP-11175 Bifidobacterium or Bifidobacterium spp. Or it is a culture supernatant, The preferable form of the said bacteria or its culture or culture supernatant is as above-mentioned.

In addition, the present invention provides Bifidobacterium longum subsp. Infantis LMG 23728 and / or Bifidobacterium breve used for suppression of TNF-α and / or IL-23 inflammatory cytokine production. (Bifidobacterium breve) It is also a Bifidobacterium bacterium of FERM BP-11175, or a culture or culture supernatant thereof, and the preferred form of the bacterium, or the culture or culture supernatant thereof is as described above.

Further, the second invention has the following preferred forms.

In a preferred form of the present invention, the composition is a pharmaceutical composition or a food or drink composition.

In a preferred embodiment of the present invention, the bacterium, or the culture or culture supernatant thereof is used for the prevention and / or improvement of one or more inflammatory diseases selected from inflammatory bowel disease, inflammatory joint disease, and inflammatory skin disease. For use in

In a preferred embodiment of the present invention, the inflammatory disease is an inflammatory disease of an infant or a child.

The third invention for solving the above-mentioned problems is to promote the expression of one or more inflammation control genes selected from the group consisting of ACE2, AgtR2, Mas-1, MKP-1, Muc-1, and IL-10 Bifidobacterium infantis (Bifidobacterium longsp. Infantis) LMG23728 and / or Bifidobacterium breve (Bifidobacterium breve) FERM BP-11175 in the manufacture of the agent or expression promoting composition The use of bacteria or a culture or culture supernatant thereof is preferred, and the preferred form of the bacteria or culture or culture supernatant is as described above.

The present invention also relates to Bifidobacterium longum subsp. Infantis LMG23728 and / or Bifidobacteria in the production of a composition for suppressing the production of inflammatory cytokines such as TNF-α and / or IL-23. Bifidobacterium breve FERM BP-11175 Bifidobacterium genus, or a culture or culture supernatant thereof. The preferred form of the bacterium, or the culture or culture supernatant is as described above. It is.

Moreover, the third invention has the following preferable forms.

In a preferred form of the present invention, the composition is a pharmaceutical composition or a food or drink composition.

In a preferred embodiment of the present invention, the bacterium, or the culture or culture supernatant thereof is used for the prevention and / or improvement of one or more inflammatory diseases selected from inflammatory bowel disease, inflammatory joint disease, and inflammatory skin disease. For use in

In a preferred embodiment of the present invention, the inflammatory disease is an inflammatory disease of an infant or a child.

In addition, a fourth invention for solving the above-mentioned problems is a Bifidobacterium infantis (Bifidobacterium longsp. Infantis) LMG23728 and / or Bifidobacterium breve (Bifidobacterium breve) FERM BP-1175. Promoting expression of one or more inflammation control genes selected from the group consisting of ACE2, AgtR2, Mas-1, MKP-1, Muc-1, and IL-10 A method for promoting the expression of one or more inflammation control genes selected from the group consisting of ACE2, AgtR2, Mas-1, MKP-1, Muc-1, and IL-10, comprising administering to a subject in need thereof Yes, the details The preferred form of the fungus or its culture or culture supernatant is as described above.

The present invention also relates to Bifidobacterium infantis (Bifidobacterium longum subsp. Infantis) LMG23728 and / or Bifidobacterium breve (FERM BP-11175 Bifidobacterium, Bifidobacterium genus, or Bifidobacterium br11 A method for inhibiting the production of inflammatory cytokines by TNF-α and / or IL-23, comprising administering a product or culture supernatant to a subject in need of inhibition of inflammatory cytokine production by TNF-α and / or IL-23 The preferred form of the bacterium or its culture or culture supernatant is as described above.

Further, the fourth invention has the following preferred forms.

In a preferred form of the present invention, the composition is a pharmaceutical composition or a food or drink composition.

In a preferred embodiment of the present invention, the bacterium, or the culture or culture supernatant thereof is used for the prevention and / or improvement of one or more inflammatory diseases selected from inflammatory bowel disease, inflammatory joint disease, and inflammatory skin disease. For use in

In a preferred embodiment of the present invention, the inflammatory disease is an inflammatory disease of an infant or a child.

According to the present invention, it is possible to provide a composition for promoting the expression of an inflammation control gene or a composition for suppressing the production of inflammatory cytokines that is safe and highly effective. According to the present invention, it is possible to provide a composition for promoting the expression of an inflammation control gene or a composition for suppressing the production of inflammatory cytokines, which is excellent in safety and particularly effective for infants and children.
In addition, according to a preferred embodiment of the present invention, since the culture supernatant is used as an active ingredient, a pharmaceutical composition or a food / drink composition using the composition for promoting the expression of inflammation control gene or the composition for suppressing inflammatory cytokine production When designing a product, it is possible to design a product that is effective without impairing the degree of freedom of prescription and raw materials.
The culture supernatant is discarded as a by-product in the industrial production of Bifidobacterium. Therefore, according to a preferred embodiment of the present invention, since the culture supernatant is used as an active ingredient, the by-product can be effectively used.

Next, a preferred embodiment of the present invention will be described in detail. However, the present invention is not limited to the following embodiments, and can be freely modified within the scope of the present invention.

Expression promoter for inflammation control gene or composition for promoting expression of inflammation control gene of the present invention (hereinafter referred to as composition for promoting expression of inflammation control gene), or expression promotion of inflammatory cytokine production inhibitor or inflammation control gene Composition (hereinafter referred to as composition for suppressing inflammatory cytokine production) is Bifidobacterium infantis LMG23728 (hereinafter referred to as B. Infantis LMG23728) and / or Bifidobacterium breve FERM BP- 11175 (hereinafter referred to as B. breve FERM BP-11175) Bifidobacterium bacterium or its culture is used as an active ingredient.

As shown in Examples described later, B.I. Infantis LMG23728 and / or B.I. The culture supernatant of Breve FERM BP-11175 has an action of promoting the expression of inflammation control genes such as ACE2, AgtR2, Mas-1, MKP-1, Muc-1, and IL-10. B. Infantis LMG23728 and / or B.I. The culture supernatant of Breve FERM BP-11175 has an inhibitory effect on the production of inflammatory cytokines such as TNF-α and IL-23. Since the culture supernatant contains metabolites of these Bifidobacterium, the culture containing the metabolite is a composition for promoting expression of inflammation control genes or a composition for suppressing inflammatory cytokine production. It can be used as an active ingredient.
Furthermore, it is considered that when the Bifidobacterium bacterium reaches the intestine in a living state, a metabolite of the Bifidobacterium bacterium is produced in the intestine and an anti-inflammatory action is exhibited. Therefore, the Bifidobacterium can also be used as an active ingredient.

B. Infantis LMG23728 or B.I. Breve FERM BP-11175 is derived from various samples containing Bifidobacterium, B. Infantis LMG23728 or B.I. Breve FERM BP-11175 can be isolated and used, or commercially available Bifidobacterium and deposited strains can also be used.

B. Infantis LMG23728 Bifidobacterium is generally available from BELGIAN CO-ORDINATED COLLECTIONS OF MICRO-ORGANISMS (BCCM).
B. Infantis LMF23728 is the same strain as M-63 (manufactured by Morinaga Milk Company).

B. Blebe FERM BP-11175, Bifidobacterium spp., Was released on August 25, 2009 by the National Institute of Technology and Evaluation Biological Center (Postal code: 292-0818, address: Kazusa, Kisarazu City, Chiba Prefecture) International deposit based on the Budapest Treaty has been made in Kamaashi 2-5-8 Room 122) and the deposit number FERM BP-11175 has been given.

The culture is B. Infantis LMG23728 and B.I. Breve FERM BP-11175 can be obtained by culturing Bifidobacterium genus bacteria by a conventional method.
The culture conditions are preferably 25 ° C. to 42 ° C. and 12 hours to several days under anaerobic conditions.
For example, a BAM medium (manufactured by Nissui) with Glucose (manufactured by Nacalai Tesque) added at a rate of 2% Infantis LMG23728 and B.I. Inoculated with Breve FERM BP-11175, cultured at 37 ° C for 12 hours under anaerobic conditions, 11% reduced skim milk powder and 0.6% yeast extract were dissolved in ion-exchanged water and autoclaved at 90 ° C for 30 minutes B. Infantis LMG23728 and B.I. A culture can be obtained by inoculating Breve FERM BP-11175 and culturing at 37 ° C. for 16 hours in an anaerobic jar (CO2: 20%, N2: 80%).

Here, the culture is a composition containing a metabolite of the genus Bifidobacterium obtained by culturing by the above-described method or the like. That is, as the culture, a composition containing the metabolite of the Bifidobacterium genus bacteria, a medium component and the microbial cells can be used as it is, and the metabolite of the Bifidobacterium bacterium is included from the composition. A fraction obtained by separation and purification by a method such as filtration, centrifugation, or extraction can also be used.
In addition, the culture may be subjected to a concentration and drying process.

It is preferable to use a culture supernatant as the active ingredient of the present invention. By using the culture supernatant as an active ingredient, the solid content derived from the culture is reduced while sufficiently maintaining the concentration of the active ingredient when designing a pharmaceutical composition or a food / beverage product composition to be described later. It is possible to increase the degree of freedom in designing pharmaceutical compositions and food / drink composition compositions.
In addition, in industrial production of Bifidobacterium genus preparations and fermented milk using the same, the culture supernatant is generally separated as a temporary light liquid and discarded. From the viewpoint of effective utilization of such by-products, the culture supernatant is preferably used.
In the present invention, the “culture supernatant” does not need to be completely removed of solid components including medium components and bacteria by a method such as centrifugation, but the metabolite of the Bifidobacterium genus is used. If the liquid layer is mainly contained, it can be said to be a “culture supernatant”.

As an active ingredient of the present invention, B. Infantis LMG23728 and / or B.I. Any single Bifidobacterium bacterium of Breve FERM BP-11175 or a culture thereof may be used, or both Bifidobacterium bacteria or a culture thereof may be used in combination.

The composition for promoting the expression of an inflammation control gene or the composition for suppressing the production of inflammatory cytokine of the present invention can be administered to mammals including humans. As the dosage form, either oral administration or parenteral administration may be selected according to the patient's symptoms and the like.

When a culture is used as the active ingredient of the present invention, the dosage of the culture depends on the dosage form and food form of the composition for promoting the expression of inflammation control genes or the composition for suppressing the production of inflammatory cytokines, patient symptoms, age, etc. Depending on the amount of solid content in the culture supernatant per day, 0.001 g / kg body weight or more, preferably 0.01 to 0.1 g / kg body weight can be used as a guide. The administration can be performed once or several times a day, and the administration period is preferably continued for several days or more.

In addition, when a Bifidobacterium bacterium is used as the active ingredient of the present invention, the dose of the microbial cell (viable bacterium) is an agent of the composition for promoting expression of inflammation control gene or the composition for suppressing inflammatory cytokine production. Although it varies depending on the shape and form of food, the patient's symptoms, age, etc., 1 × 10 ⁶ CFU / kg body weight or more per day, preferably 1 × 10 ⁷ to 1 × 10 ¹² CFU / kg body weight can be used as a guide. . CFU means a colony forming unit. When the Bifidobacterium is dead, CFU can be replaced with individual cells.

In addition, administration can be performed once or several times a day, and the administration period is preferably continued for several days or more.

The composition for promoting expression of an inflammation control gene of the present invention is capable of expressing one or more inflammation control genes selected from the group consisting of ACE2, AgtR2, Mas-1, MKP-1, Muc-1, and IL-10. Has the effect of promoting.

ACE2 converts Ang II (Angiotensin II) to Ang 1-7 in the renin-angiotensin system involved in inflammation control of intestinal tissue (Non-patent Document 1).
Here, Ang II strongly induces vasoconstriction via AT1R, and also induces active oxygen to cause oxidative stress in tissues and increase inflammatory response.
Ang1-7 is known to exert antioxidant stress and anti-inflammatory ability via AgtR2 and Mas-1 (Non-patent Document 1).

That is, by promoting the expression of an inflammation control gene selected from ACE2, AgtR2, and Mas-1, an antioxidant stress action and an anti-inflammatory ability action are exhibited.
Therefore, the composition for promoting the expression of an inflammation regulatory gene selected from ACE2, AgtR2 and Mas-1 of the present invention can be used as an antioxidant, an anti-inflammatory agent and the like.
In addition, the composition for promoting the expression of an inflammation control gene selected from ACE2, AgtR2, and Mas-1 can be used as a composition for preventing or ameliorating inflammatory bowel diseases such as ulcerative colitis and Crohn's disease.

MKP-1 (mitogen-activated protein kinase phosphatase 1) suppresses inflammation caused by TLR activation by selectively dephosphorylating p38MAPK and c-JUN terminal kinase.
Muc-1 (Mucin 1) also suppresses inflammation caused by TLR activation (Non-patent Document 4).
Therefore, by increasing the gene expression levels of MKP-1 and Muc-1, the effect of preventing or improving inflammation due to TLR activation is exhibited.
Therefore, the composition for promoting the expression of an inflammation control gene selected from MKP-1 and Muc-1 of the present invention can be used as a composition for preventing or improving inflammation due to activation of TLR.

In addition, IL-10 acts on T cells and macrophages to induce cell activation suppression and antigen presentation ability decrease, and soothes inflammation due to activation of T cells and macrophage cells. Therefore, by increasing the gene expression level of IL-10, the cell activation suppressing effect and the antigen presenting ability reducing effect are exhibited.

Therefore, the IL-10 gene expression promoting composition of the present invention can be used as a composition for preventing or improving inflammation caused by activation of T cells and macrophage cells including autoimmune diseases.
More specifically, the IL-10 gene expression promoting composition of the present invention is used as a composition for preventing or ameliorating diseases such as autoimmune hemolytic anemia, multi-gland autoimmune syndrome, and Alzheimer's disease. Can do.

The composition for suppressing inflammatory cytokine production of the present invention has an action of suppressing the production of inflammatory cytokines such as TNF-α and IL-23.

TNF-α is a kind of inflammatory cytokine, induces apoptosis through TNF receptor 1, and induces activation of transcription factors such as NF-κB or AP-1 to produce various inflammatory mediators • Increase release.
Therefore, by suppressing the production of TNF-α, the effect of preventing or improving inflammation due to the production / release of inflammatory mediators is exhibited.

IL-23 is a kind of inflammatory cytokine and induces the expression of inflammatory cytokines such as IL-17 and TNF-α. In addition, IL-23 is known to be deeply involved in inflammatory colitis, colitis, Crohn's disease, psoriasis, septic shock, etc. (Non-patent Document 3).
Therefore, by suppressing the production of IL-23, an effect of preventing or improving inflammatory bowel disease, colitis, Crohn's disease, psoriasis, septic shock, etc. is exhibited.

As described above, AngII promotes the expression of inflammatory regulatory genes such as ACE2, AgtR2, Mas-1, MKP-1, Muc-1, and IL-10 and suppresses the production of inflammatory cytokines such as TNF-α and IL-23. Inflammation caused by AT1R, inflammation caused by TLR activation, inflammation caused by T cell and macrophage cell activation, inflammation caused by production and release of various inflammatory mediators caused by TNF-α, and inflammation caused by IL-23 production The preventive or ameliorating action of a wide range of inflammatory diseases caused by the disease is exhibited.

That is, the composition for promoting expression of inflammatory regulatory genes or the composition for suppressing inflammatory cytokine production of the present invention is an inflammatory bowel disease, inflammatory skin disease, inflammatory joint disease, wound, arteriosclerotic disease, neurodegenerative disease, It can be widely used as a composition for preventing and / or improving inflammatory diseases including autoimmune diseases and tumor diseases.

Specific diseases include rheumatism, juvenile idiopathic arthritis, rheumatoid systemic lupus erythematosus, scleroderma, antiglomerular basement membrane disease, systemic lupus erythematosus, Addison's disease, antiphospholipid antibody syndrome, IgA thread Globe nephritis, Goodpasture syndrome, Lambert Eaton myasthenia syndrome, idiopathic purpura, autoimmune thyroiditis, pemphigus, autoimmune hemolytic anemia, herpes zoster dermatitis, membranous glomerulonephritis, Graves' disease , Sympathetic ophthalmitis, multigland autoimmune syndrome, multiple sclerosis, Reiter's disease, acute lung injury (ALI), Crohn's disease, myocardial infarction / cerebrovascular disorder, Alzheimer, ulcerative colitis, psoriasis, nonalcoholic Examples include fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

In the present specification, the concept of “prevention” includes reduction of the risk of developing a disease. The concept of “improvement” includes both treatment and symptom relief.

In addition, as shown in the examples described later, the active ingredient of the present invention is also excellent in the action of suppressing weight loss associated with inflammatory diseases. Therefore, the composition for promoting expression of the inflammation control gene or the composition for suppressing inflammatory cytokine production of the present invention can also be used as a composition for suppressing weight loss associated with inflammatory disease.

In addition, since the active ingredient of the present invention is a Bifidobacterium genus bacteria or a culture thereof that is present in large numbers in infants, it can be suitably used for inflammatory diseases in infants and children. Specific examples include inflammatory skin diseases such as psoriasis and inflammatory joint diseases such as juvenile idiopathic arthritis.

The composition for promoting the expression of an inflammation control gene or the composition for suppressing the production of inflammatory cytokines of the present invention can be in the form of a pharmaceutical composition or a food or drink composition.

The pharmaceutical composition of the present invention is an active ingredient of the above-mentioned composition for promoting expression of an inflammation control gene or composition for suppressing inflammatory cytokine production according to the present invention. Infantis LMG23728 and / or B.I. Breve FERM BP-11175, or a culture thereof can be prepared by formulating with any additive such as a pharmaceutically acceptable excipient.
In the case of oral administration, the pharmaceutical composition of the present invention can be in the form of solid preparations such as powders, granules, tablets and capsules, and liquids such as solutions, syrups, suspensions and emulsions. In addition, the pharmaceutical composition of the present invention can be in the form of enteral administration or parenteral administration. For example, in the case of parenteral administration, suppositories, sprays and the like can be mentioned.

As the preparation carrier and additives, various conventional organic or inorganic carriers can be used depending on the dosage form. In the case of a solid preparation, examples include excipients, binders, disintegrants, lubricants, stabilizers, and flavoring agents.

Excipients include sugar derivatives such as lactose, sucrose, glucose, mannitol, sorbit; starch derivatives such as corn starch, potato starch, α-starch, dextrin, carboxymethyl starch; crystalline cellulose, hydroxypropylcellulose, hydroxypropyl Cellulose derivatives such as methylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium magnesium metasilicate; phosphate derivatives such as calcium phosphate; And carbonate derivatives thereof; and sulfate derivatives such as calcium sulfate.

Examples of the binder include gelatin, polyvinyl pyrrolidone, and Magrogol in addition to the above excipients.

Examples of the disintegrant include, in addition to the above excipients, chemically modified starch or cellulose derivatives such as croscarmellose sodium, sodium carboxymethyl starch, and crosslinked polyvinylpyrrolidone.

Lubricants include: talc; stearic acid; stearic acid metal salts such as calcium stearate and magnesium stearate; colloidal silica; waxes such as bee gum and gallow; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid; Carboxylic acid sodium salts such as sodium sulfate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as anhydrous silicic acid and silicic acid hydrate; starch derivatives and the like .

Examples of the stabilizer include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; sorbic acid and the like.

Examples of flavoring agents include sweeteners, acidulants, and fragrances.

In the case of a liquid agent, a solvent such as water, a flavoring agent and the like can be mentioned.

In addition, when the culture is used as a pharmaceutical composition using the active ingredient, B. Infantis LMG23728 and / or B.I. The content of the culture of Breve FERM BP-11175 is 0.001 to 10% by mass, preferably 0.01 to 10% by mass, corresponding to the solid content in the culture supernatant.
In addition, in the case where a pharmaceutical composition using bacterial cells as an active ingredient is used, B. Infantis LMG23728 and / or B.I. The content of the cells of the brebe FERM BP-11175 can be 1 × 10 ⁶ CFU / kg or more, preferably 1 × 10 ⁷ to 1 × 10 ¹² CFU / kg per day.

The food and beverage composition of the present invention is, for example, B.I. Infantis LMG23728 and / or B.I. Manufactured by appropriately blending and processing Brave FERM BP-11175 or its culture with known ingredients and materials used as food hygiene acceptable bases, carriers, additives and other food additives can do. By setting it as a food / beverage product composition, an active ingredient can be ingested continuously and easily even if it is an infant or a child. In the present invention, the “food / beverage product composition” includes foods / foods consumed by humans and feeds consumed by animals other than humans.

The food and beverage composition of the present invention includes dairy products such as processed milk and fermented milk; beverages such as lactic acid bacteria beverages, soft drinks, carbonated beverages, nutritional beverages, fruit beverages (including concentrated concentrates and powders for preparation of these beverages). Ice cream, ice sherbet, shaved ice and other frozen desserts; candy, chewing gum, candy, gum, chocolate, tablet confectionery, snacks, biscuits, jelly, jam, cream, baked confectionery, etc .; enteral nutrition; functional food Or the like.
Among them, fermented milk, lactic acid bacteria beverages and the like can be produced as containing a culture of Bifidobacterium, and can also be provided in a form containing bacterial cells, so that the viewpoint of production efficiency To a preferable form.
Also, beverages (including concentrated stock solutions and powders for preparation of these beverages) such as soft drinks, carbonated beverages, nutritional beverages, fruit juice beverages, and lactic acid bacteria beverages are particularly preferred from the viewpoint of efficiently ingesting the active ingredients.
Moreover, it is also preferable that it is a granular form, a tablet form, or a liquid supplement as a form of a functional food at the point that an ingestor is easy to grasp | ascertain the intake amount of an active ingredient.

In addition, additives such as carriers, excipients, binders, disintegrants, lubricants, colorants and the like that are widely used in ordinary foods can be used in the food and drink composition of the present invention.

For example, when the form of the food or drink composition is a granular, tablet, or liquid supplement, the Bifidobacterium genus bacteria or a culture thereof, which is an active ingredient, for example, lactulose, maltitol, Sugars such as lactitol, and other sugars such as dextrin and starch; proteins such as gelatin, soy protein and corn protein; amino acids such as alanine, glutamine and isoleucine; polysaccharides such as cellulose and gum arabic; It is also preferable to formulate with oils and fats such as medium chain fatty acid triglycerides.

In addition, when the culture is used as an active ingredient, the B.V. Infantis LMG23728 and / or B.I. The content of the culture of Breve FERM BP-11175 is 0.001 to 10% by mass, preferably 0.01 to 10% by mass, corresponding to the solid content in the culture supernatant.
In addition, in the case where the bacterial cell is used as an active ingredient, B.I. Infantis LMG23728 and / or B.I. The content of the microbial cells (viable bacteria) of breve FERM BP-11175 is usually 1 × 10 ⁶ CFU / kg or more, preferably 1 × 10 ⁷ to 1 × 10 ¹² CFU / kg per day. it can. If the bacterium is dead, the CFU can be replaced with cells.

The food / beverage composition of the present invention is preferably a functional food. The “functional food” means a food on which a disease prevention effect or a disease occurrence risk reduction effect is directly or indirectly indicated. For example, foods sold in the form of foods for specified health use, functional display foods, and health supplements at present in Japan.

In addition, it is also preferable that such a functional food is in a form with a label indicating “use for prevention or improvement of inflammatory diseases”.
The “display” includes all displays having a function of informing the consumer of the use. In other words, any display capable of recalling / analyzing the use corresponds to the “display” regardless of the purpose of display, the content of display, the target object / medium to be displayed, and the like.
In addition, the “labeled” means that there is a display act of associating and recognizing the display and the food composition (product).
It is preferable that the display act is one in which the consumer can directly recognize the application. Specifically, the description of the above-mentioned use on the product or the product packaging related to the food and beverage composition of the present invention, the advertisement related to the product, the price list or transaction documents (including those provided by electromagnetic methods) The act of describing the use can be exemplified.

On the other hand, the displayed content (display content) is a display approved by the government or the like (for example, a display that is approved based on various systems determined by the government and is performed in a mode based on such approval). Is preferred.
For example, the display of health foods, functional foods and drinks, enteral nutrition foods, special purpose foods, health functional foods, foods for specified health use, functional display foods, nutritional functional foods, quasi drugs, etc. it can. In particular, the display approved by the Consumer Affairs Agency, for example, the display approved by the food system for specific health use, the functional display food, and the similar system can be exemplified.

EXAMPLES Next, although an Example is shown and this invention is demonstrated further in detail, this invention is not limited to a following example.
[Example 1]
B. The effect of administration of the culture supernatant of Infantis LMG23728 on colitis model mice was examined. The test was conducted by the following method.

(1) Test (1-1) Preparation of culture supernatant 11% reduced skim milk powder and 0.6% yeast extract were dissolved in ion exchange water and autoclaved at 90 ° C. for 30 minutes to prepare a culture medium. B. Infantis LMG23728 was inoculated, cultured in an anaerobic jar (CO2: 20%, N2: 80%) at 37 ° C for 16 hours, and the resulting culture was centrifuged as the test sample. did.

As a comparative example, Bifidobacterium longum ATCC BAA-999 (hereinafter referred to as B. longum ATCC BAA-), which is known to have an inhibitory effect on interleukin (IL) -17 production. 999) and Bifidobacterium breve LMG23729 (hereinafter referred to as B. breve LMG23729) (see Patent Document 3). For the Bifidobacterium of the comparative example, a culture supernatant was similarly prepared and used for the test.

(1-2) Animal used and test method (i) Animal used A 9-week-old CBA / J mouse (female, manufactured by Charles River Japan) was used for the test. A group of 8 mice.

(Ii) Test method Continuous administration of the culture supernatant corresponding to 10 μL / g body weight was started for 9-week-old CBA / J mice. The culture supernatant was administered to mice by intragastric administration using an oral sonde. During the test period, body weight measurement, stool property observation, and stool collection were performed every day.

6 days after administration of culture supernatant (day 7), administration of DSS (dextran sulfate sodium, manufactured by MP Biomedicals) was started in conjunction with continuous administration of culture supernatant, and preparation of DSS-induced colitis model mice started did. DSS was administered by allowing mice to drink a 3% DSS solution.

Then, body weight measurement and fecal collection were performed on the 10th day of DSS administration (16th day of culture supernatant administration), and then the mice were euthanized under anesthesia and the large intestine was collected. After measuring the length of the large intestine, the mucosa of the large intestine was collected and immediately stored frozen.

As a control, treatment similar to the above was performed except that DSS and culture supernatant were not administered, and this was used as an untreated group. In addition, the same treatment as described above was performed except that the culture supernatant was not administered, and this was designated as a fungus-free group.

(2) Method for evaluating inflammation improving effect and method for measuring expression level of inflammation control gene (2-1) Method for evaluating inflammation In Example 1, the effect of improving inflammation was expressed by (i) body weight, (ii) colon length. , (Iii) DAI, expression levels of inflammation control genes ((iv) ACE2, (v) AgtR2, (vi) Mas-1), and expression levels of inflammatory cytokines ((vii) TNF-α, (viii) IL -23).

(2-2) Method for Measuring Expression Levels of Inflammatory Regulatory Gene and Inflammatory Cytokine RNA is extracted from the colonic mucosal tissue cryopreserved in (1-2) using Trizol (Thermo Fisher Scientific) and PrimeScript RT reagent. cDNA was prepared using kit (manufactured by Takara Bio Inc.).

ACE2 primer set (SEQ ID NO: 1 (forward primer), SEQ ID NO: 2 (reverse primer)), AgTR2 (AgtR2) primer set (TAKARA BIO INC., SEQ ID NO: 3 (forward primer) using the prepared cDNA as a template ), SEQ ID NO: 4 (reverse primer)), Mas-1 (MASR) primer set (manufactured by Takara Bio Inc., SEQ ID NO: 5 (forward primer), SEQ ID NO: 6 (reverse primer)), TNF-α primer set (Takara) Bio: SEQ ID NO: 7 (forward primer), SEQ ID NO: 8 (reverse primer)), or IL-23 primer set (TAKARA BIO INC., SEQ ID NO: 9 (forward primer), SEQ ID NO: 10 (reverse primer)), and S Using BR Premix ExTaq II reagent performs quantitative PCR in real time PCR Thermal cycler (iCycler, BioRad Co.) to measure the gene expression level. Evaluation was performed by converting the measured gene expression level per GADPH expression level and standardizing it.

(3) Results The results are shown in Table 1.

(3-1) (i) Body weight, (ii) Length of large intestine, (iii) DAI (i) Body weight is the body weight of the mouse on DSS administration day 10 (culture supernatant administration day 16) / start of test The maintenance rate (%) was calculated by expressing the weight of the previous mouse as a percentage.
Further, (ii) the length of the large intestine is the length of the large intestine on the 10th day of DSS administration (16th day of culture supernatant administration).

In addition, (iii) DAI (Disease Activity Index) is closely related to the presence of tissue crypts and inflammation (see Lab Invest 69 (2): 238-249, 1993). The DAI is represented by the sum of scores (see Table 2) for the three items of weight loss rate, fecal properties, and occult blood / bleeding.
It can be evaluated that the lower the DAI, the less likely the presence of tissue crypts or inflammation.

As shown in Table 1, B. Mice administered with the culture supernatant of Infantis LMG23728 were significantly reduced in weight loss as compared to the group not administered with the bacteria. B. Mice administered with the culture supernatant of Infantis LMG23728 were significantly suppressed in weight loss most significantly as compared with mice administered with culture supernatants of other Bifidobacterium bacteria.

Also, regarding the length of the large intestine, B.I. Mice administered with the culture supernatant of Infantis LMG23728 were longer than mice administered with the fungus-free group and other culture supernatants of Bifidobacterium, and colonic contraction was significantly suppressed. It was.

In addition, compared to the mice to which the bacteria-free group and other Bifidobacterium-cultured culture supernatants were administered, B. Mice administered with the culture supernatant of Infantis LMG23728 had low DAI. That is, B.I. Mice administered with the culture supernatant of Infantis LMG23728 may be less likely to be inflamed than mice administered with the fungus-free group or mice administered with the culture supernatant of other Bifidobacterium bacteria. Indicated.

(3-2) (iv) ACE2, (v) AgtR2, (vi) About Mas-1 (iv) ACE2 (angiotensin converting enzyme 2) is a kind of carboxypeptidase. And ACE2 is known to maintain the intestinal environment by controlling amino acid absorption in the small intestine and suppress inflammatory action (Non-patent Document 2). Therefore, it can be evaluated that the higher the gene expression level of ACE2, the higher the ability to suppress the inflammatory action.

ACE2 then converts AngII (Angiotensin II) to Ang1-7 in the renin-angiotensin system (Nature, 487: 477-481, 1212).
Here, Ang II strongly induces vasoconstriction via AT1R, and also induces active oxygen to cause oxidative stress in tissues and increase inflammatory response.
In contrast, Ang1-7 has an action of antagonizing AngII. At this time, Ang1-7 is known to exert antioxidant stress and anti-inflammatory ability via AgtR2 and Mas-1 (Nature, 487: 477-481, 2012).
That is, it can be evaluated that the higher the gene expression level of AgtR2 and Mas-1, the higher the anti-inflammatory ability is exhibited.

From the results in Table 1, B. Longham ATCC BAA-999 and B.C. Compared to the mice administered with the culture supernatant of Breve LMG23729, Mice administered with the culture supernatant of Infantis LMG23728 had significantly higher ACE2 gene expression levels.

From the results in Table 1, B. Longham ATCC BAA-999 and B.C. Compared to the mice administered with the culture supernatant of Breve LMG23729, Mice administered with the culture supernatant of Infantis LMG23728 had high gene expression levels of AgtR2 and Mas-1.

(3-3) (vii) About TNF-α and (viii) IL-23 (vii) TNF-α is a kind of inflammatory cytokine, induces apoptosis through TNF receptor 1, and also exhibits NF-κB or Induction of activation of transcription factors such as AP-1 enhances production and release of various inflammatory mediators. Therefore, it can be evaluated that inflammation is less likely to occur as the gene expression level of TNF-α is lower.

(Viii) IL-23 is a kind of inflammatory cytokine, and induces the expression of inflammatory cytokines such as IL-17 and TNF-α. Therefore, it can be evaluated that inflammation is less likely to occur as the gene expression level of IL-23 decreases. In addition, IL-23 is deeply related to inflammatory colitis, colitis, Crohn's disease, psoriasis, septic shock, etc., and anti-IL-23 antibody drugs exert a marked improvement effect on inflammatory bowel disease Since it is also known (Immunity, 43: 739-750, 2015), in addition to inflammatory bowel disease by suppressing the expression of IL-23, it also against autoimmune diseases, particularly inflammatory skin diseases such as psoriasis Preventive and improvement effects can be expected.

From the results in Table 1, B. Mice administered with the culture supernatant of Infantis LMG23728 Longham ATCC BAA-999 and B.C. The gene expression levels of TNF-α and IL-23 were significantly lower than those of mice administered with the culture supernatant of Breve LMG23729.

(3-4) Consideration From the above results, B.I. In mice administered with the culture supernatant of Infantis LMG23728, ACE2 converts AngII to Ang1-7, thereby suppressing the increase in inflammation caused by AgnII and controlling the amino acid absorption in the small intestine to control the intestinal environment. It can be said that it has the effect of maintaining and strongly suppressing the inflammatory action.
B. In mice administered with the culture supernatant of Infantis LMG23728, it can be said that Ang1-7 has an effect of exerting high anti-inflammatory ability via AgtR2 and Mas-1.
B. It can be said that TNF-α and IL-23 have an effect of suppressing inflammation in mice administered with the culture supernatant of Infantis LMG23728.

From the above, B. It was found that the culture supernatant of Infantis LMG23728 has a high anti-inflammatory effect. From this, B.I. Infantis LMG23728 metabolites were found to have a high anti-inflammatory effect. Therefore, it is presumed that the same anti-inflammatory effect is exerted by allowing the Bifidobacterium itself to reach the intestine while remaining alive.
From the above, B. Infantis LMG23728 Bifidobacterium spp. Or culture thereof is effective as a composition for promoting the expression of inflammatory regulatory genes including inflammatory bowel disease and inflammatory joint disease, or a composition for suppressing inflammatory cytokine production. It can be used as a component.

[Example 2]
B. Infantis LMG23728, and B.I. The effect of administration of the culture supernatant of Breve FERM BP-11175 on colitis model mice was examined. The test was conducted by the following method.

(1-1) Preparation of culture supernatant Infantis LMG23728 and B.I. A culture supernatant of Breve FERM BP-11175 was prepared and used as a test sample.

(1-2) Animals Used and Test Method The same test was performed using the same mice as in Example 1.

(2) Evaluation Method for Inflammation Improvement Effect and Method for Measuring Expression Level of Inflammation Control Gene (2-1) Evaluation Method for Inflammation In Example 2, the improvement effect on inflammation was expressed by (i) change in body weight, (ii) length of large intestine. Now, (iii) DAI and the expression level of inflammation control genes ((ix) MKP-1, (x) Muc-1, (xi) IL-10) were evaluated.

(2-2) Method for Measuring Expression Level of Inflammation Control Gene cDNA was prepared by the same method as in Example 1. MKP-1 primer set (SEQ ID NO: 11 (forward primer), SEQ ID NO: 12 (reverse primer), manufactured by Takara Bio Inc.), Muc-1 (MUC1) primer set (SEQ ID NO: manufactured by Takara Bio Inc.) using the prepared cDNA as a template 13 (forward primer), SEQ ID NO: 14 (reverse primer)), or IL-10 primer set (SEQ ID NO: 15 (forward primer), SEQ ID NO: 16 (reverse primer), manufactured by Takara Bio Inc.), and SYBR Premix ExTaq II reagent Quantitative PCR was performed using real time PCR Thermal Cycler (iCycler, manufactured by BioRad) to measure the gene expression level. Evaluation was performed by converting and standardizing the measured gene expression level per GADPH expression level.

(3) Results Table 3 shows the results.

(3-1) (i) Body weight, (ii) Large intestine length, (iii) DAI Breve FERM BP-11175, and B.I. In mice administered with the culture supernatant of Infantis LMG23728, the decrease in body weight was significantly suppressed as compared with the non-administered group. B. Breve FERM BP-11175, and B.I. In mice administered with the culture supernatant of Infantis LMG23728, Even in comparison with mice administered with the culture supernatant of longum ATCC BAA-999, the decrease in body weight was remarkably suppressed.
In addition, regarding the length of the large intestine, B.I. Breve FERM BP-11175, and B.I. Mice to which the culture supernatant of Infantis LMG23728 was administered were not treated with bacteria or B. Compared with mice administered with the culture supernatant of Longum ATCC BAA-999, the contraction of the large intestine was significantly suppressed.

B. Breve FERM BP-11175 and B.E. Mice administered with the culture supernatant of Infantis LMG23728 each had a lower DAI compared to the group without the bacteria. In particular, B.I. The culture supernatant of Breve FERM BP-11175 had the effect of reducing the possibility of inflammation.

(3-2) (ix) MKP-1, (x) About Muc-1 (ix) MKP-1 (mitogen-activated protein kinase phosphatase 1) is a bispecific phosphatase localized in the nucleus, It is known that selective dephosphorylation of p38MAPK and c-JUN terminal kinase suppresses the production of inflammatory cytokines derived from ligand recognition by TLR. Therefore, MKP-1 can be expected to suppress sepsis, inflammatory joint diseases (rheumatic, juvenile idiopathic arthritis), and allergies.
Therefore, it can be evaluated that the higher the gene expression level of MKP-1, the higher the preventive effect on inflammatory diseases.

(X) Muc-1 (Mucin 1) is one of mucin proteins, O-glycosylated glycoprotein that constitutes a protective mucosal barrier of the epithelial surface layer in the intestinal epithelial tissue. Muc-1 protein has a function as an intracellular signal transduction molecule and is known to suppress inflammatory signals via a wide range of TLR signals (TLR2, 3, 4, 5, 7, 9). (Am J Respir Cell Mol Biol, 38: 263-268, 2008). Therefore, the increased expression of Muc-1 can be expected to have sepsis, inflammatory joint disease (rheumatic, juvenile idiopathic arthritis), and allergy suppressing effect.

Furthermore, Muc-1 is also expressed in dendritic cells and regulates or suppresses the production of inflammatory cytokines via TLR4 and TLR5 signals. That is, it can be evaluated that the higher the Muc-1 gene expression level, the higher the prevention or improvement effect of inflammatory diseases.

From the results in Table 3, B.I. More than B. longum ATCC BAA-999 culture supernatant administered mice. Breve FERM BP-11175 and B.I. MKP-1 gene expression level was significantly higher in mice administered with the culture supernatant of Infantis LMG23728.
B. In mice administered with the culture supernatant of Breve FERM BP-11175, the Muc-1 gene expression level was remarkably high.
(3-3) (xi) About IL-10 (xi) IL-10 is known to act on T cells and macrophages to suppress cell activation and reduce antigen presentation ability, thereby reducing inflammation. Yes. That is, it can be evaluated that the higher the gene expression level of IL-10, the higher the effect of preventing or improving inflammatory diseases.

From the results in Table 3, B. More than B. longum ATCC BAA-999 administered the culture supernatant. Breve FERM BP-11175 and B.I. Mice to which the culture supernatant of Infantis LMG23728 was administered had significantly higher IL-10 gene expression levels.

(3-4) Consideration From the above results, B.I. Infantis LMG23728 and B.I. In mice administered with the culture supernatant of Breve FERM BP-11175, it can be said that MKP-1 and Muc-1 strongly suppress the production of inflammatory cytokines.
B. Infantis LMG23728 and B.I. In mice administered with the culture supernatant of Breve FERM BP-11175, IL-10 acts on T cells and macrophages to induce cell activation suppression and decrease in antigen presentation ability, thereby suppressing inflammation.

Therefore, B.I. Infantis LMG23728 and B.I. It is observed that the culture supernatant of Breve FERM BP-11175 has a high anti-inflammatory effect. From this, B.I. Infantis LMG23728 and B.I. It has been found that there is a high anti-inflammatory effect on the metabolite of Breve FERM BP-11175. Therefore, it is presumed that the same anti-inflammatory effect is exerted by allowing the Bifidobacterium itself to reach the intestine while remaining alive.
From the above, B. Infantis LMG23728 and B.I. It was found that Blebe FERM BP-11175 genus Bifidobacterium or a culture thereof can be used as an active ingredient of a composition for promoting expression of an inflammation control gene or a composition for suppressing inflammatory cytokine production.

In Example 2, B. B. anti-inflammatory activity was demonstrated in Example 1 in mice administered with the culture supernatant of Breve FERM BP-11175. More than (i) change in body weight, (ii) large intestine length, (iii) DAI, and expression levels of inflammation control genes ((ix) MKP-1, () compared to mice administered with the culture supernatant of Infantis LMG23728 x) Muc-1 and (xi) IL-10) were more prominent (good) values.

That is, B. The culture supernatant of Breve FERM BP-11175 is a comparative example of Example 1. It was found to have a higher anti-inflammatory effect than the culture supernatant of Breve LMG23729.

Therefore, B. In the culture supernatant of Breve FERM BP-11175, the expression of ACE2, AgtR2, and Mas-1 which are the evaluation items of Example 1 is also shown in FIG. It can be said that the gene expression promoting effect is equal to or higher than that of the mouse administered with the culture supernatant of Infantis LMG23728. B. In the culture supernatant of Breve FERM BP-11175, the expression levels of TNF-α and IL-23, which are the evaluation items of Example 1, were measured according to B. It is recognized that it is equivalent to or less than that of the mouse administered with the culture supernatant of Infantis LMG23728, and thus it can be said that the inflammatory cytokine production inhibitory effect of TNF-α and / or IL-23 is observed.

From above, B. For Blebe FERM BP-11175 Bifidobacterium or cultures thereof, It has been found that Infantis LMG23728 has a preventive or ameliorating effect on inflammatory diseases equivalent to or higher than Bifidobacterium bacteria or cultures thereof.

[Production example]
10 g of dry powder of the culture supernatant obtained in Example 1 was added to 1 kg of reduced resistant digestible dextrin and 1 kg of sorbitol and mixed uniformly. About 2 kg of a food and beverage composition containing a culture of breve FERM BP-11175 was obtained.

According to the present invention, it is possible to provide a composition for promoting the expression of an inflammation control gene or a composition for suppressing the production of inflammatory cytokines, which has a high effect. In particular, it is possible to provide a composition for promoting the expression of an inflammation control gene or a composition for suppressing the production of inflammatory cytokines which has little resistance to infants and children and is excellent in safety.

FERM BP-11175

Claims (16)

1. Bifidobacterium infantis (Bifidobacterium longum subsp. Infantitis) LMG 23728 and / or Bifidobacterium breve (Bifidobacterium breve) FERM BP-11175 Bifidobacterium genus or effective culture thereof A composition for promoting the expression of one or more inflammation control genes selected from the group consisting of ACE2, AgtR2, Mas-1, MKP-1, Muc-1, and IL-10.
2. The said active ingredient is the culture supernatant of Bifidobacterium infantum (Bifidobacterium longum subsp. Infantis) LMG23728 and / or Bifidobacterium breve (Bifidobacterium breve) FERM BP-11175. A composition for promoting expression of an inflammation control gene.
3. 3. The composition for promoting expression of an inflammation control gene according to claim 1 or 2, wherein the composition is a pharmaceutical composition or a food or drink composition.
4. The composition according to any one of claims 1 to 3, wherein the composition is used for prevention and / or improvement of one or more inflammatory diseases selected from inflammatory bowel disease, inflammatory joint disease, and inflammatory skin disease. A composition for promoting the expression of an inflammation control gene.
5. The composition for promoting expression of an inflammation control gene according to claim 4, wherein the inflammatory disease is an inflammatory disease of an infant or a child.
6. Bifidobacterium infantis (Bifidobacterium longum subsp. Infantitis) LMG 23728 and / or Bifidobacterium breve (Bifidobacterium breve) FERM BP-11175 Bifidobacterium genus or effective culture thereof A composition for suppressing inflammatory cytokine production of TNF-α and / or IL-23.
7. The active ingredient is a culture supernatant of Bifidobacterium infantum (subsp. Infantis) LMG23728 and / or Bifidobacterium breve (FERM BP-11175). A composition for suppressing inflammatory cytokine production.
8. The composition for suppressing inflammatory cytokine production according to claim 6 or 7, which is a pharmaceutical composition or a food and drink composition.
9. The composition according to any one of claims 6 to 8, wherein the composition is used for the prevention and / or improvement of one or more inflammatory diseases selected from inflammatory bowel disease, inflammatory joint disease, and inflammatory skin disease. A composition for suppressing inflammatory cytokine production.
10. The composition for suppressing inflammatory cytokine production according to claim 9, wherein the inflammatory disease is an inflammatory disease of an infant or a child.
11. Bifidobacterium infantis used for promoting expression of one or more inflammatory control genes selected from the group consisting of ACE2, AgtR2, Mas-1, MKP-1, Muc-1 and IL-10 (Bifidobacterium longum subsp. Infantis) LMG 23728 and / or Bifidobacterium breve (Bifidobacterium breve) FERM BP-11175 Bifidobacterium genus, or a culture or culture supernatant thereof.
12. Bifidobacterium infantium (subsp. Infantis) LMG23728 and / or Bifidobacterium brMeve used to suppress the production of inflammatory cytokines by TNF-α and / or IL-23 BP-11175 Bifidobacterium, or a culture or culture supernatant thereof.
13. Bifidobacterium in the manufacture of a composition for promoting expression of one or more inflammation control genes selected from the group consisting of ACE2, AgtR2, Mas-1, MKP-1, Muc-1 and IL-10 Use of phantis (Bifidobacterium longum subsp. Infantis) LMG 23728 and / or Bifidobacterium breve (Bifidobacterium breve) FERM BP-11175 Bifidobacterium genus, or a culture or culture supernatant thereof.
14. Bifidobacterium longum subsp. Infantis LMG 23728 and / or Bifidobacterium breve (Bifidobacterium breve) in the manufacture of a composition for suppressing inflammatory cytokine production of TNF-α and / or IL-23 ) Use of FERM BP-11175 Bifidobacterium, or a culture or culture supernatant thereof.
15. Bifidobacterium infantis (Bifidobacterium longum subsp. Infantis) LMG 23728 and / or Bifidobacterium breve FERM BP-11175 Bifidobacterium spp. ACE2, comprising administering to a subject in need of enhanced expression of one or more inflammatory control genes selected from the group consisting of ACE2, AgtR2, Mas-1, MKP-1, Muc-1, and IL-10, A method for promoting the expression of one or more inflammation control genes selected from the group consisting of AgtR2, Mas-1, MKP-1, Muc-1, and IL-10.
16. Bifidobacterium longum subsp. Infantis LMG23728 and / or Bifidobacterium breve FERM BP-11175 Bifidobacterium spp. A method for suppressing inflammatory cytokine production of TNF-α and / or IL-23, comprising administering to a subject in need of suppression of inflammatory cytokine production of TNF-α and / or IL-23.