KR20230092107A - 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 a pharmaceutical composition containing the same, and more specifically, to an immunomodulatory composition 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 a bacterial strain having an immunomodulatory effect, and a composition comprising the same, and more specifically, to a composition for immunomodulation comprising a Ligilactobacillus ruminis microorganism or a culture thereof.

BACKGROUND OF THE INVENTION In the human intestine, various types of microorganisms (eg, various bacteria, fungi, viruses, etc.) inhabit and form a complex flora called the intestinal microbiome. Within these gut microbiome, microorganisms interact with each other and have various effects on the health and disease of the human host. From the results of many studies, the imbalance of the microbiome is irritable bowel syndrome, obesity, dermatitis (e.g., pyogenic infection, acne, atopic dermatitis, allergic dermatitis, contact dermatitis, etc.), depression, rheumatoid arthritis, autism spectrum disorder, It has been reported that it is related to the occurrence of various diseases such as dementia.

Various microorganisms, especially various lactic acid bacteria, are known that help maintain the intestinal microbial balance and have antibacterial and enzymatic activities. Because of this, it is known as a very useful lactic acid bacteria.

However, strains exhibiting excellent effects on immunomodulation have not yet been found. Accordingly, there is a demand for the development of novel microbial strains derived from the human intestine that can be usefully used for immunomodulation.

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

A second object of the present disclosure is to provide a culture of said microorganism.

A 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 of Ligilactobacillus ruminis LMT16-11 (accession number KCTC 14631BP) having an immunomodulatory effect.

The immunomodulation may correspond to at least one of i) regulation of T regulatory cell expression, ii) regulation of Th1 cell expression, iii) regulation of Th2 cell expression, or a combination thereof.

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

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

A third aspect provides a pharmaceutical composition for immunomodulation comprising the microorganism or a culture of the microorganism.

According to the Ligilactobacillus ruminis LMT16-11 (accession number KCTC 14631BP) microorganism having an immunomodulatory effect according to one aspect, or a culture thereof, immunomodulation can be effectively achieved.

Figure 1 shows a representative optical micrograph of Rigalactobacillus luminis LMT16-11 strain.
Figure 2 shows the amount of cytokine secretion secreted 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 present disclosure provides a Ligilactobacillus ruminis LMT16-11 microorganism having immunomodulatory efficacy. According to one aspect of the present disclosure, the splenocytes of the mouse and the strain are symbiotically cultured, and then stimulated with a T cell activating substance (eg, PMA, Ionomycin, etc.) so that an immune response occurs, and then CD4 T cell-derived cytokines As a result of the analysis, it was confirmed that immunomodulation 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 subdivided name for microorganisms previously classified as Lactobacillus ruminis . In the present disclosure, a "Rigaractobacillus species" may also be referred to as a "Lactobacillus species", and likewise a "Rigalactobacillus luminis" may also be referred to as a "Lactobacillus luminis".

In the present disclosure, "microbiome" is a compound word of microbial community (microbiota) and genome (genome), and refers to the microbial community and the entire genome coexisting in humans, animals, plants, soil, sea, lake, rock wall, air, etc.

In the present disclosure, "immunomodulation" or "modulation" (e.g., including but not limited to, modulating the expression of regulatory T cells, modulating the expression of Th1 cells, modulating the expression of Th2 cells, modulating the expression of Th17 cells, etc. ) refers to having, or having the ability to cause, a change that can be measured by an immune response.

In the present disclosure, the immunoregulation may be related to the regulation of expression of regulatory T cells (Tregs). Regulatory T cells, a type of CD4 T cells, play an essential role in suppressing autoimmune diseases and maintaining immune homeostasis. Types of regulatory T cells typically 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 the immune response through the 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, the regulation of expression of regulatory T cells may also induce or increase the secretion of cytokines such as IL-10.

In the present disclosure, the immune regulation may also be to regulate the expression of Th1 cells and Th2 cells, and Th17 cells to maintain or enhance the balance between them. Th1 cells are mainly involved in intracellular defense by 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 and Th2 cells is excessive. In general, diseases such as inflammatory bowel disease and autoimmune diseases occur when the immune response of Th1 cells is excessive, and asthma and allergic diseases occur when the immune response of Th2 cells is excessive. 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, the regulation of expression of the 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, the regulation of expression of the Th2 cells may also suppress or reduce the secretion of cytokines such as IL-4.

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

In addition, immunomodulation in the present disclosure is i) inducing or increasing the secretion of IL-10, ii) inducing or increasing the secretion of IFN-γ, iii) inhibiting or decreasing the secretion of IL-4, or a combination thereof. may be relevant. In the present disclosure, immunomodulatory efficacy may be achieved by, for example, inducing or increasing the secretion of IL-10 and IFN-γ and suppressing or reducing the 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, It may exhibit 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%, 30% to 70% relative to the control. %, 30% to 50%, 40% to 60%, 40% to 50% increase or improvement.

“Amelioration” in this disclosure refers to any action that at least reduces the severity of a parameter, eg, symptom, associated with a disease, disorder or condition.

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

In the present disclosure, "dead cells" refers to a form in which live cells and metabolites obtained through fermentation are sterilized by heating, pressurization, drug treatment, etc. as the opposite concept of live cells to prevent the growth of bacteria. "Dead cells" may also be used interchangeably with terms such as dead lactic acid bacteria, 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 present disclosure provides a culture of the microorganism.

In the present disclosure, "culture" may be used interchangeably with "culture broth" or "fermentation", and may be supplied with nutrients so that the Lactobacillus luminis LMT16-11 strain can grow and survive in vitro. It may refer to the entire medium including the strain obtained by culturing the strain in a medium for a certain period of time, metabolites thereof, and extra nutrients. The culture may refer to a culture solution obtained by culturing the strain itself, a culture solution obtained by removing the cells from the cell culture solution obtained by removing the strain, a concentrate thereof, or a lyophilized product. In one embodiment, the culture medium of the present disclosure is inoculated into a medium (eg, TSB medium, R2A medium, TSA medium, etc.) and then incubated at room temperature, for example, 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, and 6 hours to 12 hours.

Another aspect of the present disclosure provides a pharmaceutical composition for immunomodulation comprising the above microorganisms, or cultures thereof, as an active ingredient. The pharmaceutical composition may be used to prevent or treat diseases caused by immunoregulatory abnormalities, for example, 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 by further including a pharmaceutically acceptable carrier or additive in addition to the microorganism of the present disclosure, or a culture thereof. The carrier or additive may include an excipient, a stabilizer, a disintegrant, a sweetener, a binder, a coating agent, an expanding agent, a lubricant, a lubricant, a flavoring agent, a coloring agent, a diluent, a dispersing agent, a surfactant, an antioxidant, a buffer, a bacteriostatic agent, and the like. . Such carriers may include, for example, any and all aqueous and non-aqueous solutions, sterile solutions, solvents, buffers such as phosphate buffered saline (PBS) solutions, water, suspensions, emulsions suitable for pharmaceutical administration, such as oil/water emulsions, various types of wetting agents, liposomes, dispersion media and coatings. The use of such media and agents in pharmaceutical compositions is well known in the art, and compositions comprising such carriers may be formulated by well known and conventional methods.

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

“Treatment,” as used herein, refers to the healing of wounded or damaged tissue, or alteration, alteration, enhancement, amelioration, and/or beautification of a pre-existing or recognized disease, disorder, or condition to achieve a desired therapeutic outcome. Refers to the alleviation or reduction (including partial reduction, substantial reduction, near complete reduction and complete reduction), solution or prevention (whether temporary or permanent) of a disease, disorder or condition that results in achieving a result.

In the present disclosure, the composition is the above-described microorganism, or a culture thereof 1 × 10 ⁶ CFU / ml or more, 1 × 10 ⁷ CFU / ml or more, 1 × 10 ⁸ CFU / ml or more, 1 × 10 ⁹ CFU / 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. can be included with For example, a microorganism of the present disclosure, or a culture thereof, is 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 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. In addition, 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 may be contained.

In the present disclosure, prophylaxis or treatment refers to immunomodulation by 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more compared to when the composition of the present disclosure is not administered. % 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 can be up to 100% improvement.

In the present disclosure, the pharmaceutical composition may be enteral (eg, oral, feeding tube, enema), topical (eg, a nebulizer-like device for inhalation through the respiratory tract, epidermal or transdermal acting skin patch). , rectal or vaginal suppositories), and parenteral (e.g., subcutaneous, intravenous, intramuscular, intradermal, or intraperitoneal injection; buccal, sublingual, transmucosal; intranasal or intratracheal inhalation or instillation). It can be administered to a subject by any local or systemic route known in the art, including. The pharmaceutical composition may be micronized by milling or grinding a solid material, dissolved in a vehicle (eg, sterile buffered saline or water) for injection or instillation (eg, spray), applied topically, or for targeted delivery. encapsulated in liposomes or other carriers. Preferred routes include the subject's age, sex, or health condition; the nature of the disease or other pathological condition, including the number and severity of symptoms; and the active ingredient selected.

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

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

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

In the present disclosure, a microorganism of the disclosure, or a composition of the disclosure may 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 this disclosure, "an effective amount" refers to an amount sufficient to exhibit immunomodulatory efficacy in a subject when applied to a subject. The "effective amount" may vary depending on the administration method, dosage form, age and weight of the subject, severity of the disease and / or condition 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 described above per kg of body weight, or 0.1 mg to 400 mg of microorganism or culture or extract thereof per kg of body weight. In addition, the “effective amount” may be applied to 1x10 ⁶ CFU or more, 1x10 ⁷ CFU or more, 1x10 ⁸ CFU or more, or 1x10 ⁹ CFU or more per subject. For example, the strain may be applied at 1x10 ¹⁵ CFU or less, 1x10 ¹⁴ CFU or less, 1x10 ¹³ CFU or less, or 1x10 ¹² CFU or less. For example, the strain may 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 microorganism as an active ingredient, or a culture thereof, may be applied at least once a day, for example at least twice to several times.

Example

Hereinafter, the present invention will be described in more detail through examples. However, these examples are intended to illustrate the present invention by way of example, and the scope of the present invention is not limited to these examples.

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

1. Rigalactobacillus luminis ( Ligilactobacillus ruminis ) Isolation of strains

A Rigalactobacillus luminis strain was isolated from adult male feces. First, the samples were smeared on MRS medium (Difco, USA) and cultured anaerobically at 30°C. Sample pre-treatment was aseptically taken, diluted with 180 ml of 0.85% NaCl solution, and homogenized with a stomacher for 5 minutes. Thereafter, a tube containing 9 ml of 0.85% Nacl solution was prepared by sterilization, and samples were prepared by gradually diluting in the prepared tube. Thereafter, the plate was plated on the MRS plate medium and cultured at 37° C. for 2 to 3 days, and the colonies that appeared were distinguished according to shape and color, and then purified again. Thereafter, the 16s rRNA gene sequences of the strains were read by sequencing.

2. Identification of Rigalactobacillus luminis strains

(1) Analysis of morphological characteristics

The selected Rigalactobacillus luminis strain was cultured in MRS plate medium (Difco, USA), and colony morphology was observed. The colony morphology in the MRS plate medium of the selected Rigalactobacillus luminis strain 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 +

1 shows a representative optical micrograph of the selected Rigalactobacillus luminis LMT16-11 strain. As shown in FIG. 1, the Ractobacillus luminis LMT16-11 strain was a rod-shaped bacillus and was similar in character to a typical Racillus genus.

(2) 16S rDNA analysis

The 16S rRNA gene of the isolated Rigalactobacillus luminis LMT16-11 strain was amplified, and the nucleotide sequence of the amplified 16S rRNA gene was analyzed. The amplification was performed by PCR using the genomic DNA of the LMT16-11 strain as a template and the oligonucleotide of SEQ ID NO: 1 and the oligonucleotide of SEQ ID NO: 2 (Bionics Co., Ltd.) as primer sets. 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 luminis LMT16-11 had 99.93% sequence identity with the Ligilactobacillus ruminis species. In addition, as a result of phylogenetic tree analysis, Rigalactobacillus luminis LMT16-11 was the same as Rigalactobacillus luminis species. As a result, the Rigalactobacillus luminis LMT16-11 strain was identified as a new strain belonging to the Rigalactobacillus luminis species.

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

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

1. Sugar fermentation characteristics of Rigalactobacillus luminis LMT16-11 strain

The sugar metabolism characteristics of the selected Rigalactobacillus luminis LMT16-11 strain were confirmed using an API 50 CHL kit (BioMetrieux, France) according to the supplier's experimental method. Table 2 shows the sugar fermentation characteristics of the confirmed Rigalactobacillus 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-Melibiose + + 31 D-saccharose + + 32 D-Trehalose - - 33 inulin - - 34 D-Melezitos - - 35 D-Raffinose + + 36 amidone - - 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 Rigalactobacillus luminis LMT16-11 strain

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

Antibiotics at concentrations of 1000 units/ml penicillin and 1000ug/ml streptomycin were administered to a 96-well plate to prevent overgrowth of the Rigalactobacillus luminis LMT16-11 strain and mouse splenocytes during symbiotic culture. And, after culturing for 8 hours at 37 ℃, 5% CO ₂ condition, it was observed under a microscope to establish appropriate culture conditions.

2. Symbiotic culture of Rigalactobacillus luminis LMT16-11 strain and mouse spleen cells

In order to evaluate the immune response of mouse spleen cells against Rigalactobacillus 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. Thereafter, in order to maintain minimal viability for the evaluation of the immune response of spleen cells, a low concentration of anti-CD3 antibody concentration of 0.05ug/ml was coated on a 96-well plate, and then 3x10 ⁵ cells of spleen cells per well and previously prepared The Rigalactobacillus luminis LMT16-11 strain was cultured symbiotically for 72 hours.

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

The immune response by the Rigalactobacillus luminis LMT16-11 strain and its metabolites was evaluated through cytokine analysis of spleen cell-derived immune cells cultured in symbiosis. In order to observe the intracellular signal generation pattern of spleen cell-derived immune cells, splenocytes cultured in symbiosis with Ractobacillus luminis LMT16-11 strain for 72 hours were cultured in RPMI1640 medium containing 10% FBS for 50 days. Stimulation was performed for 4 hours with ng/ml PMA (Phorbol 12-myristate 13-acetate) and 500 ng/ml Ionomycin. PMA and ionomycin substances are substances that give 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 increases PKC (protein kinase C) as a Ca2+ ionophore, and in the case of PMA, it phosphorylates PKC to synergize to target CD4 T cells. For immune cell analysis after stimulation, cells were stained with the antibodies 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 secreted from spleen cell-derived CD4 T cells as a percentage compared to the control group. CD4 T cells are one of the main 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 FIG. 2 , it can be seen that IFN-γ increased significantly by about 2-fold and IL-10 increased by about 5-fold compared to the control group that was not treated with Rigalactobacillus luminis LMT16-11. Taken together, it was confirmed that the Rigalactobacillus luminis LMT16-11 strain induces the activation response of Th1 and regulatory T cells and relatively suppresses the Th2 response, indicating that the Rigalactobacillus luminis LMT16-11 strain of the present disclosure suggesting that it has immunomodulatory effects.

Korea Research Institute of Bioscience and Biotechnology KCTC14631BP 20210630

<110> Medytox Inc. <120> Bacterial strain which has immunomodulatory effect, and pharmaceutical compositions comprising the same <130> 57-KR-GN-1 <160> 3 <170> KoPatentIn 3.0 <210> 1 <211> 20 <212> DNA <213> artificial sequence <220> <223> primer <400> 1 agagtttgat cmtggctcag 20 <210> 2 <211> 22 <212> DNA <213> artificial sequence <220> <223> primer <400> 2 tacggytacc ttgttacgac tt 22 <210> 3 <211> 1416 <212> DNA <213> Lactobacillus ruminis <400> 3 cgaatgcttg cattcaccga aagaagctta gtggcgaacg ggtgagtaac acgtaggcaa 60 cctgcccaaa agagggggat aacacttgga aacaggtgct aataccgcat aaccatgaac 120 accgcatgat gttcatgtaa aagacggctt ttgctgtcac ttttggatgg gcctgcggcg 180 tattaacttg ttggtggggt aacggcctac caaggtgatg atacgtagcc gaactgagag 240 gttgatcggc cacattggga ctgagacacg gcccaaactc ctacgggagg cagcagtagg 300 gaatcttcca caatggacga aagtctgatg gagcaacgcc gcgtgaatga agaaggcctt 360 cgggtcgtaa aattctgttg tcagagaaga acgtgcgtga gagtaactgt tcacgtattg 420 acggtatctg accagaaagc cacggctaac tacgtgccag cagccgcggt aatacgtagg 480 tggcgagcgt tgtccggatt tattgggcgt aaagggaacg caggcggtct tttaagtctg 540 atgtgaaagc cttcggctta accgaagtag tgcattggaa actggaagac ttgagtgcag 600 660 ggaagaacac cagtggcgaa agcggctctc tggtctgtaa ctgacgctga ggttcgaaag 720 cgtgggtagc aaacaggatt agataccctg gtagtccacg ccgtaaacga tgagtgctaa 780 gtgttggagg gtttccgccc ttcagtgctg cagctaacgc attaagcact ccgcctgggg 840 agtacggtcg caagactgaa actcaaagga attgacgggg gcccgcacaa gcggtggagc 900 atgtggttta attcgaagca acgcgaagaa ccttaccagg tcttgacatc ttctgacaat 960 tccagagatg gaacgttccc ttcggggaca gaatgacagg tggtgcatgg ttgtcgtcag 1020 ctcgtgtcgt gagatgttgg gttaagtccc gcaacgagcg caacccttat tgtcagttgc 1080 catcattaag ttgggcactc tggcgagact gccggtgaca aaccggagga aggtggggat 1140 gacgtcaaat catcatgccc cttatgacct gggctacaca cgtgctacaa tggacggtac 1200 aacgagtcgc taactcgcga gggcaagcta atctcttaaa gccgttctca gttcggattg 1260 caggctgcaa ctcgcctgca tgaagtcgga atcgctagta atcgcgaatc agcatgtcgc 1320 ggtgaatacg ttcccgggcc ttgtacacac cgcccgtcac accatgagag tttgtaacac 1380 ccaaagtcgg tggggtaacc tttggagcca gccgcc 1416

Claims (5)

Ligilactobacillus ruminis LMT16-11 (accession number KCTC 14631BP) microorganism having immunomodulatory effect. The group of claim 1, wherein the immunomodulatory effect corresponds to at least one of i) regulatory T cell expression regulation, ii) Th1 cell expression regulation, iii) Th2 cell expression regulation, or a combination thereof. Lactobacillus luminis ( Ligilactobacillus ruminis ) LMT16-11 microorganisms. The method of claim 2, wherein the immunomodulation comprises at least one of i) inducing or increasing the secretion of IL-10, ii) inducing or increasing the secretion of IFN-γ, iii) inhibiting or decreasing the secretion of IL-4, or a combination thereof. Corresponding to the Rigilactobacillus Luminis ( Ligilactobacillus ruminis ) LMT16-11 microorganisms. A culture of the microorganism according to any one of claims 1 to 3. Claims 1 to 3 of any one of the microorganism, or a pharmaceutical composition for immunomodulation, comprising a culture thereof.

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