KR102627018B1 - Bacterial strain which has immunomodulatory effect, and pharmaceutical compositions comprising the same - Google Patents

Abstract

The present disclosure relates to bacterial strains with immunomodulatory effects and compositions containing them, and more specifically, to compositions for immunomodulation containing Ligilactobacillus ruminis microorganisms, or cultures thereof.

Description

Bacterial strain which has immunomodulatory effect, and pharmaceutical compositions comprising the same}

The present disclosure relates to bacterial strains with immunomodulatory effects and compositions containing them, and more specifically, to compositions for immunomodulation containing Ligilactobacillus ruminis microorganisms, or cultures thereof.

The human intestine is home to a wide range of different types of microorganisms (e.g., various bacteria, fungi, viruses, etc.), forming a complex flora called the intestinal microbiome. Within these intestinal microbiomes, microorganisms interact with each other and have various effects on the health and disease of human hosts. Many studies have shown that microbiome imbalance is associated with irritable bowel syndrome, obesity, dermatitis (e.g., purulent infection, acne, atopic dermatitis, allergic dermatitis, contact dermatitis, etc.), depression, rheumatoid arthritis, autism spectrum disorder, It has been reported to be related to the occurrence of various diseases, including dementia.

Several microorganisms, especially various lactic acid bacteria, are known to help maintain the balance of intestinal microorganisms and have antibacterial and enzymatic activities. Among these, Lactobacillus species have strains that can suppress harmful bacteria through the secretion of lactic acid. Therefore, it is known as a very useful lactic acid bacteria.

However, strains showing excellent effects on immune regulation have not yet been discovered. Accordingly, there is a need for the development of new microbial strains derived from the human intestine that can be usefully used for immune regulation.

Lactobacillus saerimneri and Lactobacillus ruminis: novel human-derived probiotic strains with immunomodulatory activities (FEMS Microbiol Lett. 2009 April; 293(1): 65-.72.).

The first object of the present disclosure is to provide Ligilactobacillus ruminis LMT16-11 (accession number KCTC 14631BP) microorganism with immunomodulatory effect.

A second object of the present disclosure is to provide a culture of the above microorganisms.

The third object of the present disclosure is to provide a pharmaceutical composition for immunomodulation, comprising the microorganism or its culture.

The first aspect provides a microorganism, Ligilactobacillus ruminis LMT16-11 (Accession Number KCTC 14631BP), which has immunomodulatory effects.

The immunomodulation may correspond to one or more of i) regulating the expression of regulatory T cells, ii) regulating the expression of Th1 cells, iii) regulating the expression of Th2 cells, or a combination thereof.

In addition, the immunomodulation corresponds to one or more of i) inducing or increasing secretion of IL-10, ii) inducing or increasing secretion of IFN-γ, iii) inhibiting or decreasing secretion of IL-4, or a combination thereof. You can.

A second aspect provides a culture of the above-described microorganism.

The third aspect provides a pharmaceutical composition for immunomodulation comprising the above-mentioned microorganism or a culture of the above-mentioned microorganism.

According to one aspect, Ligilactobacillus ruminis LMT16-11 (Accession No. KCTC 14631BP) microorganism with immunomodulatory effect, or a culture thereof, immunomodulation can be effectively achieved.

Figure 1 shows a representative optical microscope photo of Rigi lactobacillus luminis LMT16-11 strain.
Figure 2 shows the amount of cytokine secretion from spleen cell-derived CD4 T cells as a percentage compared to the control group.

Hereinafter, the present invention will be described in detail.

One aspect of the disclosure provides Ligilactobacillus ruminis LMT16-11 microorganism with immunomodulatory efficacy. According to one aspect of the present disclosure, the strain is co-cultured with mouse spleen cells, then stimulated with a T cell activating agent (e.g., PMA, Ionomycin, etc.) to generate an immune response, and then CD4 T cell-derived cytokines are produced. As a result of the analysis, it was confirmed that immune regulation can be induced by inducing regulatory T cells and Th1 responses and relatively suppressing Th2 responses.

Ligilactobacillus ruminis is a member of the Lactobacillus salivarius clade and is a detailed name for microorganisms previously classified as Lactobacillus ruminis . In the present disclosure, “Ligilactobacillus spp.” may also be referred to as “Lactobacillus spp.” Likewise, “Ligilactobacillus ruminis” may also be referred to as “Lactobacillus ruminis.”

In the present disclosure, “microbiome” is a compound word of microbial community (microbiota) and genome, and refers to the entire microbial community and genome that coexist with humans, animals and plants, soil, sea, lakes, rock walls, and the atmosphere.

In the present disclosure, “immunomodulation” or “modulation” (including but not limited to, e.g., regulating the expression of regulatory T cells, regulating the expression of Th1 cells, regulating the expression of Th2 cells, regulating the expression of Th17 cells, etc. ) refers to something that causes or has the ability to cause changes that can be measured by an immune response, or the ability to do so.

In the present disclosure, the immunomodulation may be related to regulating the expression of regulatory T cells (Treg). Regulatory T cells are a type of CD4 T cells and play an essential role in suppressing autoimmune diseases and maintaining immune homeostasis. Typical types of regulatory T cells include Foxe+ Treg cells that express the Foxp3 transcription factor, Tr1 cells that do not express Foxp3 but secrete IL-10, Th3 cells that secrete TGF-β, and Qa1-restricted CD8 Treg cells. It exists and regulates immune responses through secretion of cytokines such as IL-10 and TGF-β.

In one embodiment of the present disclosure, the immunomodulation may be regulating the expression of regulatory T cells, more preferably, inducing or increasing the expression of regulatory T cells. More preferably, controlling the expression of the regulatory T cells may also, for example, induce or increase the secretion of cytokines such as IL-10.

In the present disclosure, the immune regulation may also be regulating the expression of Th1 cells and Th2 cells, and Th17 cells to maintain or improve the balance between them. Th1 cells are mainly involved in intracellular defense through phagocytosis and secrete cytokines such as IL-12, IFN-γ, and T-bet. Th2 cells are responsible for extracellular defense and secrete cytokines such as IL-4, IL-5, and IL-13. Diseases occur when the immune response of Th1 cells and Th2 cells is excessive. Generally, when the immune response of Th1 cells is excessive, diseases such as inflammatory bowel disease and autoimmune diseases occur, and when the immune response of Th2 cells is excessive, asthma or allergic diseases occur. It is known to occur. In addition, Th17 cells are responsible for autoimmunity and cellular defense and secrete cytokines such as RORγt, IL-6, IL-8, IL-17, and IL-22.

In one embodiment of the present disclosure, the immunomodulation may be regulating the expression of Th1 cells, more preferably, inducing or increasing the expression of Th1 cells. More preferably, regulating the expression of Th1 cells may also induce or increase the secretion of cytokines, such as INF-γ.

In one embodiment, the immunomodulation may be regulating the expression of Th2 cells, more preferably suppressing or reducing the expression of Th2 cells. More preferably, regulating the expression of Th2 cells may also inhibit or reduce the secretion of cytokines such as IL-4.

In one embodiment, the immunomodulation may correspond to one or more of i) regulating the expression of regulatory T cells, ii) regulating the expression of Th1 cells, iii) regulating the expression of Th2 cells, or a combination thereof. Preferably, immunomodulation in the present disclosure may refer to inducing or increasing expression of regulatory T cells and Th1 cells and suppressing or decreasing expression of Th2 cells.

Additionally, immunomodulation in the present disclosure refers to one or more of i) inducing or increasing secretion of IL-10, ii) inducing or increasing secretion of IFN-γ, iii) inhibiting or reducing secretion of IL-4, or combinations thereof. It may be applicable. In the present disclosure, immunomodulatory efficacy may be achieved, for example, by inducing or increasing secretion of IL-10 and IFN-γ and inhibiting or reducing secretion of IL-4.

In the present disclosure, the immunomodulatory efficacy is 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, compared to the control group not treated with Rigi lactobacillus luminis LMT16-11. It may indicate an increase or improvement in immunomodulatory efficacy of 80% or more, 90% or more, or 100%. For example, the immunomodulatory efficacy is 10% to 90%, 20% to 80%, 20% to 70%, 20% to 50%, 30% to 90%, 30% to 60%, and 30% to 70% compared to the control group. It may indicate an increase or improvement of %, 30% to 50%, 40% to 60%, or 40% to 50%.

In the present disclosure, “improvement” refers to any action that at least reduces the severity of a disease, disorder, or parameter associated with a condition, such as a symptom.

In one aspect, the Ligilactobacillus ruminis LMT16-11 microorganism may be live or dead.

In the present disclosure, “dead cells” are the opposite concept of live cells and refer to a form in which live cells and metabolites obtained through fermentation are sterilized by heating, pressurizing, drug treatment, etc. to prevent bacterial growth. “Dead cells” can also be used interchangeably with terms such as dead lactic acid bacteria cells, cultures of lactic acid bacteria, extracts of lactic acid bacteria, lysates of lactic acid bacteria, and components of lactic acid bacteria cells.

Another aspect of the disclosure provides a culture of the microorganism.

In the present disclosure, “culture” may be used interchangeably with “culture medium” or “fermentation,” which is a substance capable of supplying nutrients to allow the Rigi lactobacillus ruminis LMT16-11 strain to grow and survive in vitro. It may refer to the entire medium containing the strain, its metabolites, extra nutrients, etc. obtained by culturing the strain in the medium for a certain period of time. The culture may refer to the culture solution itself obtained by cultivating the strain, the culture solution obtained by removing the bacterial cells from the bacterial culture solution obtained by removing the strain, a concentrate thereof, or a freeze-dried product. In one embodiment, the culture medium of the present disclosure is inoculated with a strain into a medium (e.g., TSB medium, R2A medium, TSA medium, etc.) and then incubated at room temperature, e.g., at a temperature between 10° C. and 40° C., for a certain period of time, e.g. For example, it may be obtained by culturing for 1 hour to 48 hours, 10 hours to 48 hours, 10 hours to 24 hours, 12 hours to 24 hours, or 6 hours to 12 hours.

Another aspect of the present disclosure provides a pharmaceutical composition for immunomodulation comprising the above-described microorganism or a culture thereof as an active ingredient. The pharmaceutical composition can be used to prevent or treat diseases caused by immune regulation abnormalities, including, but not limited to, one or more selected from the group consisting of infectious diseases, inflammatory diseases, obesity, and cancer.

In one embodiment, the composition may be formulated to further include a pharmaceutically acceptable carrier or additive in addition to the microorganism of the present disclosure or its culture. The carrier or additive may include excipients, stabilizers, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, lubricants, flavoring agents, coloring agents, diluents, dispersants, surfactants, antioxidants, buffers, bacteriostatic agents, etc. . The carrier may be, for example, any and all aqueous and non-aqueous solutions, sterile solutions, solvents, buffers, such as phosphate buffered saline (PBS) solutions, water, suspensions, emulsions, for example, suitable for pharmaceutical administration. These can be oil/water emulsions, various types of wetting agents, liposomes, dispersions and coatings. The use of such media and agents in pharmaceutical compositions is well known in the art, and compositions containing such carriers can be formulated by well-known and conventional methods.

“Prevention” in this disclosure refers to delaying the onset of a disease, disorder or condition.

In this disclosure, “treatment” refers to the desired therapeutic effect by healing injured or damaged tissue or altering, altering, strengthening, improving, ameliorating and/or beautifying a pre-existing or recognized disease, disorder or condition. Refers to the alleviation or reduction (including partial reduction, significant reduction, almost complete reduction and complete reduction), resolution or prevention (whether temporary or permanent) of a disease, disorder or condition, so as to achieve a result.

In the present disclosure, the composition contains the above-mentioned microorganisms, or a culture thereof, at least 1×10 ⁶ CFU/ml, at least 1×10 ⁷ CFU/ml, at least 1×10 ⁸ CFU/ml, at least 1×10 ⁹ CFU/ml. It can contain more than ml. For example, the microorganism of the present disclosure, or a culture thereof, is 1×10 ¹⁵ CFU/ml or less, 1×10 ¹⁴ CFU/ml or less, 1×10 ¹³ CFU/ml or less, 1×10 ¹² CFU/ml or less. It can be included as . For example, the microorganism of the present disclosure, or a culture thereof, is grown at 1×10 ⁶ to 1×10 ¹⁵ CFU/ml, 1×10 ⁷ to 1×10 ¹⁴ CFU/ml, 1×10 ⁸ to 1×10 ¹³ It may be included in an amount of CFU/ml, 1×10 ⁹ to 1×10 ¹² CFU/ml, 1×10 ¹⁰ to 1×10 ¹² CFU/ml, and 1×10 ¹¹ to 1×10 ¹² CFU/ml. Additionally, it may contain 0.01 to 50% by weight, or 0.1 to 20% by weight, of the microorganism or its culture based on the weight of the composition.

In the present disclosure, prevention or treatment involves immunomodulation by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, 35%, or more. % or more, 45% or more, 50% or more, 55% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 100% or more, 5% to 100%, 10 % to 100%, 20% to 100%, 30% to 100%, 40% to 100%, 50% to 100%, 60% to 100%, 70% to 100%, 80% to 100%, or 90% It may be an improvement of up to 100%.

In the present disclosure, the pharmaceutical composition may be administered enterally (e.g., orally, feeding tube, enema), topically (e.g., a device such as a nebulizer for inhalation through the respiratory tract, or a skin patch that acts epidermally or transdermally). , suppositories that act rectally or vaginally), and parenterally (e.g., subcutaneous, intravenous, intramuscular, intradermal, or intraperitoneal injection; buccal, sublingual, transmucosal; intranasal or bronchial inhalation or instillation). It can be administered to a subject by any topical or systemic route known in the art, including: Pharmaceutical compositions may be micronized by milling or pulverizing solid materials, dissolved in a vehicle (e.g., sterile buffered saline or water) for injection or instillation (e.g., nebulization), applied topically, or for targeted delivery. It may be encapsulated in liposomes or other carriers. The preferred route depends on the subject's age, gender, or health status; The nature of the disease or other pathological condition, including the number and severity of symptoms; and may vary depending on the active ingredient selected.

In the present disclosure, the subject can be a mammal. The mammal may be, but is not limited to, a human, dog, cat, horse, or pig.

Another aspect of the disclosure provides a method of modulating immunity in a subject comprising applying to the subject a microorganism of the disclosure, or a composition of the disclosure.

In this disclosure, “application” means providing a microorganism of this disclosure, or a composition of this disclosure, to a subject. Microorganisms of the disclosure, or compositions of the disclosure, can be applied by a variety of suitable routes known in the art.

In the present disclosure, the microorganisms of the disclosure, or the compositions of the disclosure can be applied in an effective amount. In the present disclosure, an “effective amount” refers to an amount sufficient to achieve a beneficial or desired result as described herein when applied to a subject. In the context of the present disclosure, an “effective amount” refers to an amount sufficient to produce an immunomodulatory effect in a subject when applied to the subject. The “effective amount” may vary depending on the administration method, formulation, age and weight of the subject, and the severity of the disease and/or condition to which it is applied, and may vary according to the judgment of experts in the medical and veterinary fields. For example, the “effective amount” may be 0.01 mg to 200 mg of the microorganism or culture or extract thereof per kg of body weight, or 0.1 mg to 400 mg of the microorganism or culture or extract thereof per kg of body weight. In addition, the “effective amount” may be applied as more than 1x10 ⁶ CFU, more than 1x10 ⁷ CFU, more than 1x10 ⁸ CFU, and more than 1x10 ⁹ CFU per subject. For example, the strain can be applied at 1x10 ¹⁵ CFU or less, 1x10 ¹⁴ CFU or less, 1x10 ¹³ CFU or less, and 1x10 ¹² CFU or less. For example, the strain can be applied at 1x10 ⁶ CFU to 1x10 ¹⁵ CFU, 1x10 ⁷ CFU to 1x10 ¹⁴ CFU, 1x10 ⁸ CFU to 1x10 ¹³ CFU, 1x10 ⁹ CFU to 1x10 ¹² CFU, 1x10 ¹⁰ CFU to 1x10 ¹² CFU. . In the present disclosure, the active ingredient, the microorganism, or its culture may be applied once or more times a day, for example, two or more times or divided into several times.

Example

Hereinafter, the present invention will be described in more detail through examples. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.

Example 1: Isolation and identification of Rigi lactobacillus luminis LMT16-11 strain

1. Rigoractobacillus ruminis ( Ligilactobacillus ruminis ) Isolation of strains

Rigi lactobacillus ruminis strain was isolated from adult male feces. First, the sample was spread on MRS medium (Difco, USA) and cultured anaerobically at 30°C. The sample pretreatment method was aseptically taken, diluted with 180 ml of 0.85% NaCl solution, and homogenized for 5 minutes with a stomacher. Afterwards, a tube containing 9 ml of 0.85% Nacl solution was prepared by sterilizing it, and samples were prepared by stepwise dilution into the prepared tube. Afterwards, it was plated on MRS plate medium and cultured at 37°C for 2 to 3 days, and the colonies that appeared were distinguished by shape and color and purified again. Afterwards, the 16s rRNA gene base sequences of the strains were deciphered through sequencing.

2. Identification of Rigi lactobacillus ruminis strains

(1) Analysis of morphological characteristics

The selected Rigi lactobacillus luminis strains were cultured on MRS plate medium (Difco, USA) and the morphology of colonies was observed. The colony morphology of the selected Rigi lactobacillus luminis strains on MRS plate medium is shown in Table 1 below.

LMT16-11 form circle size 1.0-1.5mm color cream color opacity opacity bump convex surface Rough surface aerobic growth - anaerobic growth +

Figure 1 shows a representative optical microscope photograph of the selected Rigi lactobacillus luminis LMT16-11 strain. As shown in Figure 1, the Ligilactobacillus ruminis LMT16-11 strain was a rod-shaped bacillus and was similar to the typical characteristics of the Rigilactobacillus genus.

(2) 16S rDNA analysis

The 16S rRNA gene of the isolated Rigilactobacillus luminis LMT16-11 strain was amplified, and the nucleotide sequence of the amplified 16S rRNA gene was analyzed. The amplification was accomplished by performing PCR using the LMT16-11 strain genomic DNA as a template and using the oligonucleotide of SEQ ID NO: 1 and the oligonucleotide of SEQ ID NO: 2 (Bionics Co., Ltd.) as a primer set. The 16S rDNA nucleotide sequence of the isolated LMT16-11 strain is shown in SEQ ID NO: 3. The nucleotide sequence of the identified 16S rDNA was compared with the nucleotide sequence of known 16S rDNA using EZBioCloud (https://www.ezbiocloud.net/). As a result, the 16S rDNA of Ligilactobacillus ruminis LMT16-11 had 99.93% sequence identity with the species Ligilactobacillus ruminis . In addition, as a result of phylogenetic tree analysis, Ligilactobacillus ruminis LMT16-11 was identical to the Rigiractobacillus ruminis species. As a result, the Ligilactobacillus ruminis LMT16-11 strain was confirmed as a new strain belonging to the Rigilactobacillus ruminis species.

The present inventors named LMT16-11 lactic acid bacteria as " Ligilactobacillus ruminis LMT16-11" (accession number KCTC 14631BP) and transferred it to the Korea Collection for Type Cultures (KCTC) at the Korea Research Institute of Bioscience and Biotechnology. Deposited on June 30, 2021.

Example 2: Analysis of physiological activity characteristics of Rigi lactobacillus luminis LMT16-11 strain

1. Sugar fermentation characteristics of Rigi lactobacillus luminis LMT16-11 strain

The sugar metabolism characteristics of the selected Rigi lactobacillus luminis LMT16-11 strain were confirmed using the API 50 CHL kit (BioMetrieux, France) according to the supplier's experimental method. Table 2 shows the sugar fermentation characteristics of the identified Rigi lactobacillus luminis LMT16-11 strain.

number carbohydrate LMT16-11 24 hours 48 hours One glycerol - - 2 Erythritol - - 3 D-arabinose - - 4 L-arabinose - - 5 D-ribose - - 6 D-xylose - - 7 L-xylose - - 8 D-Adonitol - - 9 Methyl-βD-xylopyranoside - - 10 D-galactose + + 11 D-glucose + + 12 D-fructose + + 13 D-mannose + + 14 L-sorbose - - 15 L-rhamnose - - 16 Dulcitol - - 17 inositol - - 18 Mannitol - - 19 D-Sorbitol - - 20 Methyl αD-mannopyranoside - - 21 Methyl αD-glucopyranoside - - 22 N-Acetylglucosamine + + 23 Amygdalin - - 24 arbutin - - 25 Esculin - - 26 salicin - - 27 D-cellobiose + + 28 D-maltose + + 29 D-Lactose + + 30 D-Mellibiose + + 31 D-Saccharose + + 32 D-Trehalose - - 33 Inulin - - 34 D-Melegitos - - 35 D-raffinose + + 36 amidon - - 37 glycogen - - 38 xylitol - - 39 gentiobios - - 40 D-Turanos - - 41 D-lyxose - - 42 D-Tagatose - - 43 D-fucose - - 44 L-fucose - - 45 D-arabitol - - 46 L-arabitol - - 47 Potassium Glunate - - 48 Potassium 2-ketogluconate - - 49 Potassium 5-ketoglunate - -

Example 3: Evaluation of anti-inflammatory response of Rigi lactobacillus luminis LMT16-11 strain

1. Establishment of culture conditions for Rigi lactobacillus luminis LMT16-11 strain

When cultivating the symbiotic relationship between Ligilactobacillus luminis LMT16-11 strain and mouse spleen cells, antibiotics at a concentration of 1000 unit/ml penicillin and 1000ug/ml streptomycin were administered to a 96-well plate to prevent overgrowth of Ligilactobacillus luminis LMT16-11 strain. Appropriate culture conditions were established by observing under a microscope after culturing for 8 hours at 37°C and 5% CO ₂ conditions.

2. Symbiotic culture between Rigi lactobacillus luminis LMT16-11 strain and mouse spleen cells

In order to evaluate the immune response of mouse spleen cells caused by the Rigylactobacillus luminis LMT16-11 strain, C57BL/6 mice (male, 20-22 g) were purchased from Orient Bio Co., Ltd., and their spleens were removed. The extracted spleen was separated into single cells by removing red blood cells, and then spleen cells were obtained. Afterwards, in order to maintain the minimum survival for evaluating the immune response of spleen cells, a 96-well plate was coated with a low concentration of anti-CD3 antibody, 0.05ug/ml, and then 3x10 ⁵ spleen cells per well were added to the previously prepared spleen cells. Rigi lactobacillus luminis LMT16-11 strain was cultured commensally for 72 hours.

3. Evaluation of immune response of spleen cells by Rigi lactobacillus luminis LMT16-11 strain

Immune responses caused by Rigipactobacillus luminis LMT16-11 strain or metabolites were evaluated through cytokine analysis of spleen cell-derived immune cells co-cultured with Rigipactobacillus luminis LMT16-11 strain. To observe the intracellular signal generation pattern of spleen cell-derived immune cells, spleen cells co-cultured with Rigi lactobacillus luminis LMT16-11 strain for 72 hours were cultured for 50 min in RPMI1640 medium containing 10% FBS. Stimulation was performed with ng/ml PMA (Phorbol 12-myristate 13-acetate) and 500 ng/ml Ionomycin for 4 hours. PMA and ionomycin are substances that provide signal stimulation to activate T cells, and play the same role as the activation mechanism of T cells by actual antigens, creating an environment in which an immune response occurs. Ionomycin is a Ca2+ ionophore that increases PKC (protein kinase C), and in the case of PMA, it acts as a synergizer to target CD4 T cells by phosphorylating PKC. For immune cell analysis after stimulation, cells were stained with the antibodies listed in Table 3 and analyzed using CANTO II flow cytometry equipment.

explanation target color surface marker CD45 PE-Cy7 TCRb APC-Cy7 CD4 PerCP-Cy5.5 CD8 Pacific blue Intracellular staining IFN-γ FITC IL-4 APC IL-10 PE

Figure 2 shows the amount of cytokine secretion from spleen cell-derived CD4 T cells as a percentage compared to the control group. CD4 T cells are one of the key indicators of immune response, and IFN-γ, IL-4, and IL-10 are functional cytokines that indicate activation of Th1 immune cells, activation of Th2 immune cells, and activation of regulatory T cells, respectively. . As shown in Figure 2, it can be seen that compared to the control group that was not treated with Rigylactobacillus luminis LMT16-11, the level of IFN-γ increased significantly by about 2-fold and the level of IL-10 increased by about 5-fold. In summary, it was confirmed that the Rigylactobacillus luminis LMT16-11 strain induces an activation response of Th1 and regulatory T cells and relatively suppresses the Th2 response, which means that the Rigipacillus luminis LMT16-11 strain of the present disclosure This suggests that it has immunomodulatory effects.

Korea Research Institute of Bioscience and Biotechnology KCTC14631BP 20210630

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Claims (5)

Ligilactobacillus ruminis LMT16-11 (accession number KCTC 14631BP) is a microorganism with immunomodulatory effect, and the immunomodulatory effect is achieved by inducing or increasing the expression of regulatory T cells and Th1 cells and suppressing or suppressing the expression of Th2 cells. Microorganisms, corresponding to being reduced. delete The method of claim 1, wherein the immunomodulatory effect is achieved by inducing or increasing the secretion of IL-10 and IFN-γ and suppressing or decreasing the secretion of IL-4. Ligilactobacillus ruminis ) LMT16-11 microorganism. A culture of the microorganism according to any one of claims 1 or 3, wherein the culture is a microorganism, a culture medium, a concentrate thereof, or a freeze-dried product of the microorganism. delete