Composition and method for preventing, alleviating, or treating liver injury

Abstract

The present invention relates to a composition for preventing, alleviating or treating liver injury, for example, nonalcoholic fatty liver, and more specifically, it relates to a composition for preventing or treating liver injury comprising a Ruminococcus spp. strain.

Description

ŧ 7 [DESCRIPTION] TITLE OF THE INVENTION COMPOSITION AND METHOD FOR PREVENTING, ALLEVIATING, OR TREATING LIVER INJURY TECHNICAL FIELD The present invention relates to a composition for preventing, alleviating or treating liver injury and a method for preventing, alleviating or treating liver injury. [BACKGROUND ART] Nonalcoholic fatty liver disease (NAFLD) is characterized by liver disease of metabolic disorder leading from simple steatosis, to nonalcoholic steatohepatitis which is an aggressive tissue form that ultimately leads to advanced fibrosis and liver cirrhosis. The global prevalence of NAFLD is estimated to be 24-30% in most epidemiological studies, and is increasing in parallel with obesity and metabolic syndrome. Recently, increased interest has focused on identifying and understanding specific roles of the intestinal microbiota in various metabolic diseases. Gut dysbiosis, which refers to abnormal changes in the intestinal microbiota compared to the normal microbiota, is related to reduction of bacteria producing beneficial short-chain fatty acid (SCFA), changes in the composition of bile acids, activation of immune reactions to lipopolysaccharide (LPS), an increase of ethanol • 4 ŧ production by overgrowth of ethanol producing bacteria, and conversion of phosphatidylcholine into choline and trimethylamine. Changes in the gut microbiome affecting the gut-liver axis are known to contribute to progression of chronic liver disease such as NAFLD and liver cirrhosis, and advanced fibrosis. However, recovering the abundance of gut microbiome which is enriched or depleted in the disease state does not always alleviate the severity of the disease. Because the changes of the gut microbiome in the disease state might be a result of physiological changes induced by the disease not a cause. Therefore, there is a need for an effective method for preventing, treating and diagnosing NAFLD, which can determine the histological severity of NAFLD and define changes in the gut microbiome well. [DISCLOSURE] TECHNICAL PROBLEM The present invention is intended to solve the above problems, and an object thereof is to provide a composition for preventing, alleviating or treating liver injury, for example, nonalcoholic fatty liver disease. TECHNICAL SOLUTION One embodiment of the present invention relates to a composition for preventing, alleviating or treating of liver injury, comprising a Ruminococcus spp. strain. Another embodiment of the present invention relates to a composition for culturing a ١ 4 Ruminococcus spp. strain comprising carbon source and nitrogen source. Other embodiment of the present invention relates to a method for preventing, alleviating or treating liver injury, comprising administering the composition for preventing, alleviating or treating liver injury according to the present invention to a subject in need thereof. Hereinafter, the present invention will be described in more detail. One embodiment of the present invention relates to a composition for preventing, alleviating or treating liver injury, comprising a Ruminococcus spp. strain. The composition may be a pharmaceutical composition or food composition. The composition may further comprise butyric acid. The liver injury may be one or more selected from the group consisting of fatty liver, hepatitis, liver fibrosis and liver cirrhosis. The liver injury may be nonalcoholic liver injury. Specifically, the hepatitis may be nonalcoholic steatohepatitis, and the fatty liver may be nonalcoholic fatty liver. The nonalcoholic fatty liver may be non-obese nonalcoholic fatty liver, obese nonalcoholic fatty liver, or diabetic nonalcoholic fatty liver, but not limited thereto. The diabetic nonalcoholic fatty liver may be caused by type 2 diabetes. Type 2 diabetes patients have nonalcoholic steatohepatitis (NASH) with a 40% chance, and type 2 diabetes patients having nonalcoholic fatty liver has higher prevalence of nonalcoholic steatohepatitis (80.2% vs. 64.4%; p < 0.001) and liver fibrosis (40.3% vs. 17.0%; p < 0.001) compared to nonalcoholic fatty liver patients without type 2 diabetes. Therefore, there is a need to ١ • develop a therapeutic agent for nonalcoholic fatty liver patients having type 2 diabetes. The liver injury with type 2 diabetes is difficult to treat because the prognosis is pooper than that in case of not having type 2 diabetes, however, the composition according to the present invention can treat the liver injury with type 2 diabetes. The composition may prevent, alleviate or treat liver injury independently of insulin. In the present Examples, as the result of confirming the liver injury effect of the composition according to the present invention using an animal model having insulin resistance, liver injury was significantly alleviated, and thus, it was confirmed that the composition according to the present invention alleviated and treated liver injury independently of insulin. The composition according to the present invention shows a significantly improved effect of treating liver injury, by being administered to a subject with liver injury. The subject with liver injury may have one or more of characteristics of the following (1) to (5): (1) increased condition of blood ALT concentration, for example, over 1 time, 1.1 times or more, 1.2 times or more, 1.3 times or more, 1.4 times or more, 1.5 times or more, 1.6 times or more, 1.7 times or more, 1.8 times or more, 1.9 times or more, 2 times or more, 2.1 times or more, 2.2 times or more, 2.3 times or more, 2.4 times or more, 2.5 times or more, 2.6 times or more, 2.7 times or more, 2.8 times or more, 2.9 times or more, 3 times or more, 3.5 times or more, 4 times or more, 4.5 times or more, 5 times or more, 5.5 times or more, 6 times or more, 6.5 times or more, 7 times or more, 7.5 times or more, 8 times or more, 8.5 times or more, 9 times or more, 9.5 times or more, or 10 times or more of the blood ALT concentration of a normal control group. Į (2) increased condition of blood AST concentration, for example, over 1 time, 1.1 times or more, 1.2 times or more, 1.3 times or more, 1.4 times or more, 1.5 times or more, 1.6 times or more, 1.7 times or more, 1.8 times or more, 1.9 times or more, 2 times or more, 2.1 times or more, 2.2 times or more, 2.3 times or more, 2.4 times or more, 2.5 times or more, 2.6 times or more, 2.7 times or more, 2.8 times or more, 2.9 times or more, 3 times or more, 3.5 times or more, 4 times or more, 4.5 times or more, 5 times or more, 5.5 times or more, 6 times or more, 6.5 times or more, 7 times or more, 7.5 times or more, 8 times or more, 8.5 times or more, 9 times or more, 9.5 times or more, or 10 times or more of the blood AST concentration of a normal control group. (3) reduced condition of secondary bile acid concentration in cecum, for example, less than 1 time, 0.9 times or less, 0.8 times or less, 0.7 times or less, 0.6 times or less, 0.5 times or less, 0.4 times or less, 0.3 times or less, 0.2 times or less, or 0.1 times or less of the secondary bile acid concentration in cecum of a normal control group. (4) increased condition of fibrosis marker gene expression, for example, over 1 time, 1.1 times or more, 1.2 times or more, 1.3 times or more, 1.4 times or more, 1.5 times or more, 1.6 times or more, 1.7 times or more, 1.8 times or more, 1.9 times or more, 2 times or more, 2.1 times or more, 2.2 times or more, 2.3 times or more, 2.4 times or more, 2.5 times or more, 2.6 times or more, 2.7 times or more, 2.8 times or more, 2.9 times or more, 3 times or more, 3.5 times or more, 4 times or more, 4.5 times or more, 5 times or more, 5.5 times or more, 6 times or more, 6.5 times or more, 7 times or more, 7.5 times or more, 8 times or more, 8.5 times or more, 9 times or more, 9.5 times or more, 10 times or more, 11 times or more, 12 times or more, 13 times or more, 14 ٦ ŧ ι times or more, 15 times or more, 16 times or more, 17 times or more, 18 times or more, 19 times or more, or 20 times or more overexpressed of the fibrosis marker gene expression of a normal control group, in which the fibrosis marker gene may be one or more selected from the group consisting of Colla1, Timp1, and <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-SMA. (5) increased condition of liver weight ratio to body weight, for example, over 1 time, 1.1 times or more, 1.2 times or more, 1.3 times or more, 1.4 times or more, 1.5 times or more, 1.6 times or more, 1.7 times or more, 1.8 times or more, 1.9 times or more, 2 times or more, 2.1 times or more, 2.2 times or more, 2.3 times or more, 2.4 times or more, 2.5 times or more, 2.6 times or more, 2.7 times or more, 2.8 times or more, 2.9 times or more, or 3 times or more of the liver weight ratio to body weight of a normal control group. The normal control group refers to a control group not having liver injury. In addition, the liver injury of the subject may be one or more selected from the group consisting of fatty liver, hepatitis, liver fibrosis and liver cirrhosis. The liver injury may be nonalcoholic liver injury. Specifically, the hepatitis may be nonalcoholic steatohepatitis, and the fatty liver may be nonalcoholic fatty liver. The nonalcoholic fatty liver may be non-obese nonalcoholic fatty liver, obese nonalcoholic fatty liver, or diabetic nonalcoholic fatty liver, but not limited thereto. The composition according to the present invention may be administered to a subject with diabetes, and in particular, the composition according to the present invention can prevent, alleviate or treat liver injury independently of insulin, and therefore, it may be administered to a ٦ • ſ subject with type 2 diabetes. In the present Examples, as the result of confirming an effect of treating liver injury, for example, nonalcoholic fatty liver, of the composition according to the present invention, the therapeutic effect such as ability of reducing blood ALT concentration, ability of reducing blood AST concentration, ability of reducing the ratio of liver to body weight, and the like, is significantly excellent compared to the therapeutic effect shown in the model without type 2 diabetes, and this means that the composition according to the present invention has an excellent therapeutic effect particularly in a type 2 diabetes subject. In particular, the therapeutic effect in the subject with type 2 diabetes is more excellent, and the difference in insulin resistance played an important role in the difference in sensitivity related to alleviation or treatment of liver injury by Ruminococcus. The composition according to the present invention may be administered to a subject having liver damage to generate one or more of characteristics of the following (1) to (5): (1) reducing blood ALT concentration, for example, the blood ALT concentration when the composition is administered is less than 100%, 99% or less, 98% or less, 97% or less, 96% or less, 95% or less, 94% or less, 93% or less, 92% or less, 91% or less, 90% or less, 80% or less, 70% or less, 65% or less, 60% or less, 59% or less, 58% or less, 50% or less, 45% or less, or 40% or less, based on 100% of the blood ALT concentration of the control group not administered with the composition (As one example, in FIG. 1b, when co-administering MCD and Ruminococcus faecis strain, 39.21% of ALT level was shown compared to single administration of MCD.) (2) reducing blood AST concentration, for example, the blood AST concentration when the composition is administered is less than 100%, 99% or less, 98% or less, 97% or less, 96% or less, 95% or less, 94% or less, 93% or less, 92% or less, 91% or less, 90% or less, 80% or less, 70% or less, 65% or less, 64% or less, 63% or less, 62% or less, 61% or less, 60% or less, or 59% or less, based on 100% of the blood AST concentration of the control group not administered with the composition (As one example, in FIG. 1b, when co-administering MCD and Ruminococcus faecis strain, 57.52% of AST level was shown compared to single administration of MCD.) (3) increasing secondary bile acid (for example, cecal secondary bile acid) concentration, for example, the secondary bile acid concentration when the composition is administered is over 100%, 105% or more, 110% or more, 115% or more, 120% or more, 125% or more, 130% or more, 135% or more, 140% or more, 145% or more, 150% or more, 160% or more, 170% or more, 180% or more, 190% or more, or 200% or more, based on 100% of the secondary bile acid concentration of the control group not administered with the composition (As one example, in FIG. 1i, when co- administering MCD and Ruminococcus faecis strain, 217.50% of LCA concentration and 143.37% of DCA concentration were shown compared to single administration of MCD.) (4) reducing fibrotic gene expression, for example, when the composition is administered, the expression of the fibrosis-related gene, for example, one or more of Collal, Timpl, and <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>- SMA, is less than 100%, 99% or less, 98% or less, 97% or less, 96% or less, 95% or less, 94% or less, 93% or less, 92% or less, 91% or less, 90% or less, 80% or less, 78% or less, 75% or less, 70% or less, 65% or less, or 60% or less, based on 100% of the expression of the control group 1. not administered with the composition (As one example, in FIG. 1h, when co-administering MCD and Ruminococcus faecis strain, 90.60% of Collal expression, 77.17% of α-SMA expression, and 58.50% of Timp1 expression were shown compared to single administration of MCD.) (5) reducing liver weight ratio to body weight, for example, the liver weight ratio to body weight when the composition is administered is less than 100%, 99% or less, 98% or less, 97% or less, 96% or less, 95% or less, 94% or less, 93% or less, 92% or less, 91% or less, 90% or less, 89% or less, 88% or less, or 87% or less, based on 100% of the liver weight ratio to body weight of the control group not administered with the composition (As one example, in FIG. 1g, when co- administering MCD and Ruminococcus faecis strain, 86.27% of the liver ratio was shown compared to single administration of MCD.) The control group not administered with the composition refers to a non-administration group which has the same disease, but the composition according to the present invention is not administered thereto. The secondary bile acid may be one or more selected from the group consisting of deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA). The fibrotic gene may be one or more selected from the group consisting of Collal, Timpl, and <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-SMA. The composition according to the present invention may be administered to a subject having liver injury and having insulin resistance, for example, a subject having type 2 diabetic liver injury, and generate one or more of characteristics of the following (1) to (3): 1 ŧ (1) reduction ratio of the ALT level of over 1 time, 1.1 times or more, 1.2 times or more, 1.3 times or more, 1.4 times or more, 1.5 times or more, 1.6 times or more, 1.7 times or more, 1.8 times or more, 1.9 times or more, 2 times or more, 2.1 times or more, 2.2 times or more, 2.3 times or more, 2.4 times or more, 2.5 times or more, or 2.6 times or more, compared to a control group not having insulin resistance, (2) reduction ratio of the AST level of over 1 time, 1.1 times or more, 1.2 times or more, 1.3 times or more, 1.4 times or more, 1.5 times or more, 1.6 times or more, 1.7 times or more, 1.8 times or more, 1.9 times or more, 2 times or more, 2.1 times or more, or 2.2 times or more, compared to a control group not having insulin resistance, (3) reduction ratio of the liver weight ratio to body weight of over 1 time, 1.1 times or more, 1.2 times or more, 1.3 times or more, 1.4 times or more, 1.5 times or more, 2 times or more, 3 times or more, 4 times or more, 5 times or more, 6 times or more, 7 times or more, 8 times or more, 9 times or more, or 10 times or more, compared to a control group not having insulin resistance. In the present invention, the term 'active ingredient' means an ingredient which can show desired activity alone or show the activity together with a carrier having no activity by itself. In the present invention, the term 'prevention' means inhibiting or delaying occurrence of illness, disorder or disease. When the occurrence of illness, disorder or disease is inhibited or delayed during a predetermined period, prevention may be considered complete. In the present invention, the term 'treatment' means partially or completely alleviating, ŧ improving, relieving, inhibiting or delaying a specific illness, disorder and / or disease or symptom according to the disease, and reduce the severity or reduce incidence of one or more symptoms or characteristics. The pharmaceutical composition of the present invention may further comprise one or more of active ingredients showing the same or similar function in addition to the active ingredient. In addition, the pharmaceutical composition according to the present invention may be prepared in a unit dose form or prepared by being inserted into a multidose container, by formulating it using a pharmaceutically acceptable carrier, according to a method which may be clearly conducted by those skilled in the art to which the present invention pertains. In the present invention, the term 'carrier' means a compound that facilitates addition of a compound into a cell or tissue, and the term 'pharmaceutically acceptable' refers to a composition which is physiologically acceptable and when administered to a human, generally, does not cause an allergic reaction such as gastrointestinal disorder, dizziness or a similar reaction thereto. The pharmaceutically acceptable carrier is commonly used in formulation, and it comprises lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinyl pyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxylbenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil, and the like, but not limited thereto. In addition, the pharmaceutical composition according to the present invention may further comprise an additive such as a filler, an anti-coagulant, a lubricant, a wetting agent, a 1 ţ flavoring, an emulsifier, a preservative, and the like, in addition to the ingredients. In the present invention, the content of the additive comprised in the pharmaceutical composition may not be particularly limited, and it may be appropriately adjusted within the content range used in common formulation. Furthermore, the pharmaceutical composition according to the present invention may be formulated in an oral formulation. The non-limitative examples of the oral formulation may comprise tablets, troches, lozenge, aqueous suspension, oily suspension, formulated powder, granules, emulsion, hard capsules, soft capsules, syrup or elixirs, or the like. In order to formulate the pharmaceutical composition according to the present invention for oral administration, a binder such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose or gelatin; an excipient such as dicalcium phosphate; a disintegrating agent such as corn starch or sweet potato starch; magnesium stearate, calcium stearate, sodium stearyl fumarate, and the like may be used, and a sweetener, a flavoring agent, a syrup, and the like may also be used. Moreover, in case of capsules, a liquid carrier such as fat oil, and the like may be further used in addition to the aforementioned substances. In the present invention, the term 'excipient' means any substance, which is not a therapeutic agent, and refers to one which is used as a carrier or medium for delivery of a therapeutic agent or is added to a pharmaceutical composition. Thereby, it may improve handling and storage characteristics or allow and facilitate dosage unit formation of the composition. The pharmaceutical composition according to the present invention may be used by being 1 formulated in various forms such as oral formulations comprising liquid, suspension, powder, granules, tablets, capsules, pills, extract, emulsion, syrup, aerosol, and the like, and injections of sterile injection solution, and it may be orally administered, or be administered through various routes comprising intravenous, intraperitoneal, subcutaneous, intrarectal, and topical administration, and the like. In the present invention, the term 'oral administration' means that an active ingredient is administered to the gastrointestinal tract for absorption, that is, a substance prepared for digestion. A preferable dosage of the pharmaceutical composition according to the present invention may have various ranges depending on the patient's condition and body weight, age, gender, health status, dietary constitution specificity, properties of a formulation, degree of disease, administration time of the composition, administration method, administration period or interval, excretion rate and drug form, and may be appropriately selected by those skilled in the art. In the present invention, the term 'effective dosage of a pharmaceutical composition' refers to an amount of the composition of an active ingredient sufficient to treat a specific symptom. This may vary depending on the formulation method, administration method, administration time and / or administration route of the pharmaceutical composition, and this may vary depending on various factors comprising the type or degree of the response to be achieved by administration of the pharmaceutical composition, the type, age, body weight, general health status, symptoms or degree of disease, gender, diet, excretion of a subject to be administered, and components of drugs or other compositions used together simultaneously or at once to the corresponding subject, and 1 ì 1 . similar factors well-known in the pharmaceutical field, and those skilled in the art may readily determine and prescribe an effective dosage for desired treatment. The administration of the pharmaceutical composition according to the present invention may be administered once a day, and may be administered divided into several times. The composition may be administered as an individual therapeutic agent or administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agent. Taking all of the above factors into consideration, it may be administered in an amount that can obtain the maximum effect with a minimum amount without side effects. For example, the composition according to the present invention may be administered in a daily dose of 0.001 to 10,000 mg, 0.001 to 5,000 mg, 0.001 to 1,000 mg, 0.001 to 500 mg, 0.001 to 300 mg, 0.001 to 100 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 1 mg, 0.001 to 0.5 mg, 0.001 to 0.1 mg, 0.001 to 0.05 mg, 0.001 to 0.01 mg, 0.01 to 10,000 mg, 0.01 to 5,000 mg, 0.01 to 1,000 mg, 0.01 to 500 mg, 0.01 to 300 mg, 0.01 to 100 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to 1 mg, 0.01 to 0.5 mg, 0.01 to 0.1 mg, 0.01 to 0.05 mg, 0.1 to 10,000 mg, 0.1 to 5,000 mg, 0.1 to 1,000 mg, 0.1 to 500 mg, 0.1 to 300 mg, 0.1 to 200 mg, 0.1 to 100 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to 1 mg, 0.1 to 0.5 mg, 1 to 10,000 mg, 1 to 5,000 mg, 1 to 1,000 mg, 1 to 500 mg, 1 to 300 mg, 1 to 200 mg, 3 1 1 1 to 100 mg, 1 to 50 mg, 1 to 10 mg, 1 to 5 mg, 10 to 10,000 mg, 10 to 5,000 mg, 10 to 1,000 mg, 10 to 500 mg, 10 to 300 mg, 10 to 200 mg, 10 to 100 mg, 10 to 50 mg, 10 to 40 mg, 10 to 30 mg, 10 to 20 mg, 100 to 10,000 mg, 100 to 5,000 mg, 100 to 1,000 mg, 100 to 500 mg, 100 to 300 mg, or 100 to 200 mg per 1kg body weight, but not limited thereto. As one example, the daily dose of the composition according to the present invention may be 0.001 to 10 g / lday, 0.001 to 5 g / lday, 0.01 to 10 g / lday, or 0.01 to 5 g / lday, based on oral administration of an adult patient. In addition, the total daily dose may be divided and administered continuously or non-continuously if necessary. The composition according to the present invention may further comprise a freeze-drying protective agent. The freeze-drying protective agent may comprise one or more selected from the group consisting of monosaccharides, disaccharides, polysaccharides, carbohydrates, minerals, amino acids, sucrose, calcium phosphate, arginine, sodium chloride, fructose, potassium phosphate monobasic, potassium phosphate dibasic and trehalose. The sucrose may be added to the freeze-drying protective agent by 100 to 300 g / L, 100 to 250 g / L, 100 to 200 g / L, 150 to 300 g / L, 150 to 250 g / L, 150 to 200 g / L, 200 to 300 g / L, or 200 to 250 g / L, and as one example, it may be added by 200 g / L. The calcium phosphate may be added to the freeze-drying protective agent at a concentration of 5 to 20 g / L, 5 to 15 g / L, 5 to 12 g / L, 5 to 11 g / L, 7 to 20 g / L, 7 to 15 g / L, 7 to 12 g / L, 7 to 11 g / L, 10 to 20 g / L, 10 to 15 g / L, 10 to 12 g / L, or 10 to 11 g / L, and as one example, it may be added by 10.5 g / L. The amino acid may be added to the freeze-drying protective agent at a concentration of 1 to 10 g / L, 1 to 8 g / L, 1 to 6 g / L, 1 to 5 g / L, 3 to 10 g / L, 3 to 8 g / L, 3 to 6 g / L, 3 to 5 g / L, 4 to 10 g / L, 4 to 8 g / L, 4 to 6 g / L, or 4 to 5 g / L, and as one example, it may be added by 4 g / L. The sodium chloride may be added to the freeze-drying protective agent at a concentration of 0.1 to 5 g / L, 0.1 to 3 g / L, 0.1 to 1 g / L, 0.5 to 5 g / L, 0.5 to 3 g / L, or 0.5 to 1 g / L, and as one example, it may be added by 0.8 g / L. The Ruminococcus spp. strain according to the present invention may be Ruminococcus faecis. As one example, the Ruminococcus spp. strain may be Ruminococcus faecis having accession number KCTC no. 5757 (original biological deposit date of 21 January 2009). In the present description, the Ruminococcus faecis having accession number KCTC no. 5757 may be represented by Ruminococcus faecis KBL1028. The strain may continue to grow after 8 hours of culturing, 9 hours of culturing, 10 hours of culturing, 11 hours of culturing, 12 hours of culturing, 13 hours of culturing, or 14 hours of culturing, in a culture medium with a carbon source concentration of 5 to 30% (w / v), a nitrogen source concentration of 50 to 90% (w / v), a mineral concentration of 5 to 15% (w / v), and an amino acid concentration of 0.1 to 10% (w / v). The strain may have excellent culture efficiency in FMK1028 medium having the composition according to Table 3. For example, the strain may be characterized that absorbance after cultured in FMK1028 medium having the composition according to Table 3 is higher than absorbance after culture in one or more selected from the group consisting of YBHI medium, GAM medium, MRS medium, BL medium, and RCM medium. As one example, the strain may be one ). • r 1 in which the number of viable cells per unit volume after 14 hours of culturing in FMK1028 medium having the composition according to Table 3 is 10 times or more, 50 times or more, 100 times or more, 150 times or more, 200 times or more, 250 times or more, 300 times or more, 350 times or more, 400 times or more, 450 times or more, 500 times or more, 550 times or more, or 600times or more, when cultured in YBHI medium. Other embodiment of the present invention relates to a composition for culturing a Ruminococcus spp. strain comprising carbon source and nitrogen source. The carbon source may be one or more selected from the group consisting of glucose, sucrose, fructose, lactose, maltose, molasses and galactose. The nitrogen source may be one or more selected from the group consisting of yeast extract, soy peptone, skim milk, tryptone, casamino acids, potato peptone, pea peptone, wheat peptone, broadbean peptone, papaic soy peptone, and lupin peptone. Other embodiment of the present invention relates to a composition for culturing a Ruminococcus spp. strain, comprising carbon source and nitrogen source. The carbon source may be at a concentration of 5 to 30% (<com:Math><semantics>w / v<annotation encoding="application / x-tex">w / v< / annotation>< / semantics>< / com:Math>), and the nitrogen source may be at a concentration of 50 to 90% (w / v). The Ruminococcus spp. strain is as described above. The carbon source may comprise one or more selected from the group consisting of glucose, sucrose, fructose, lactose, maltose, molasses and galactose. The nitrogen source may comprise one or more selected from the group consisting of yeast extract, soy peptone, skim milk, tryptone, casamino acids, potato peptone, pea peptone, wheat peptone, broadbean peptone, papaic soy peptone, and lupin peptone. 1 ٠ · Comment of the comment of the comment of the comment of the comment of the comment of the comment of the comment of the comment of the comment of the comment of the comment of the comment of the comment of the comment of The composition for culturing a Ruminococcus spp. strain may facilitate growth after 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours or 14 hours of culturing of the Ruminococcus spp. strain. The composition for culturing a Ruminococcus spp. strain may further comprise one or more selected from the group consisting of minerals, amino acids, vitamins, nucleic acids, and inorganic salts. The mineral may comprise one or more selected from the group consisting of sodium acetate, sodium chloride, sodium phosphate monobasic, sodium phosphate dibasic, potassium chloride, magnesium sulfate, and manganese sulfate. The amino acid may comprise L-cysteine, L-leucine, L-isoleucine, L-valine, L-tryptophan, L-threonine, L-phenylalanine, and L-methionine. The concentration of the carbon source may be 5 to 30% (<com:Math><semantics>w / v<annotation encoding="application / x-tex">w / v< / annotation>< / semantics>< / com:Math>), and the concentration of the nitrogen source may be 50 to 90% (w / v), and the concentration of the mineral may be 5 to 15% <com:Math><semantics>(w / v)<annotation encoding="application / x-tex">(w / v)< / annotation>< / semantics>< / com:Math>, and the concentration of the amino acid may be 0.1 to 10% <com:Math><semantics>(w / v)<annotation encoding="application / x-tex">(w / v)< / annotation>< / semantics>< / com:Math>. Other embodiment of the present invention relates to a method for culturing a Ruminococcus spp. strain, comprising inoculating a Ruminococcus spp. strain to the composition for culturing a Ruminococcus spp. strain according to the present invention, and culturing it. The method for culturing may facilitate growth after 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours or 14 hours of culturing of the Ruminococcus spp. strain. The culturing may be a static culture, a fed-batch culture or a batch culture, but not limited 1 1 1 . thereto. Other embodiment of the present invention relates to a method for preventing, alleviating or treating liver injury, comprising administering the composition for preventing, alleviating or treating liver injury according to the present invention to a subject in need thereof. The composition may comprise a Ruminococcus spp. strain. The composition for preventing, alleviating or treating liver injury, the Ruminococcus spp. strain and the like are as described above. The subject is a subject having liver injury, and the subject having liver injury is as described above. For example, the subject having liver injury may be a subject having insulin resistance, and as one example, it may be a subject having diabetes, specifically, a subject having type 2 diabetes.

ADVANTAGEOUS EFFECTS

Claims

We Claim:

1. A pharmaceutical or food agent for preventing, alleviating or treating nonalcoholic fatty liver disease, comprising a Ruminococcus faecis strain with accession number KCTC5757.

2. The agent according to claim 1, wherein the nonalcoholic fatty liver disease has one or more characteristics of the following (1) to (5): (1) increased blood alanine aminotransferase (ALT) concentration compared to a control group not having nonalcoholic fatty liver disease, (2) increased blood aspartate aminotransferase (AST) concentration compared to the control group not having nonalcoholic fatty liver disease, (3) reduced secondary bile acid concentration in cecum compared to the control group not having nonalcoholic fatty liver disease, (4) increased fibrotic gene expression compared to the control group not having nonalcoholic fatty liver disease, and (5) increased ratio of liver weight to body weight compared to the control group not having nonalcoholic fatty liver disease.

3. The agent according to claim 1, wherein the nonalcoholic fatty liver disease is diabetic nonalcoholic fatty liver.

4. The agent according to claim 1, wherein the agent is characterized by one or more 1 . , • characteristics of the following (1) to (5): (1) reducing blood alanine aminotransferase (ALT) concentration compared to a control group not administered with the agent, (2) reducing blood aspartate aminotransferase (AST) concentration compared to the control group not administered with the agent, (3) increasing secondary bile acid concentration in cecum compared to the control group not administered with the agent, (4) reducing fibratic gene expression compared to the control group not administered with the agent, and (5) reducing ratio of liver weight to body weight compared to the control group not administered with the agent.

5. The agent according to claim 4, wherein the secondary bile acid is one or more selected from the group consisting of deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA), or wherein the fibrotic gene is one or more selected from the group consisting of Colla1, Timp1, and <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-SMA.

6. The agent according to claim 1, wherein the agent alleviates or treats nonalcoholic fatty liver disease independently of insulin.

7. The agent according to claim 1, wherein the agent is for administration to a subject 7 having insulin resistance.

8. The agent according to claim 1, wherein the agent is for administration to a subject having insulin resistance and is characterized by one or more of the following (1) to (3): (1) higher reduction ratio of blood alanine aminotransferase (ALT) level compared to a control group having no insulin resistance, (2) higher reduction ratio of blood aspartate aminotransferase (AST) level compared to a control group having no insulin resistance, and (3) higher reduction ratio of a ratio of liver weight to body weight compared to a control group having no insulin resistance.

9. The agent according to claim 1, wherein the strain continues to grow after 8 hours of culturing in a culture medium including 5 to 30% (w / v) of carbon source concentration, 50 to 90% (w / v) of nitrogen source concentration, 5 to 15% (w / v) of mineral concentration, and 0.1 to 10% (w / v) of amino acid concentration.

10. The agent according to claim 1, wherein the agent further comprises a freeze-drying protective agent.

11. The agent according to claim 10, wherein the freeze-drying protective agent is at least one selected from the group consisting of sucrose, calcium phosphate, arginine, sodium chloride, fructose, potassium phosphate monobasic, potassium phosphate dibasic, and 1. • trehalose. • 12. Use of the agent as defined by any one of claim 1 to 11 for preventing, alleviating or treating nonalcoholic fatty liver disease, wherein the agent is for administration to a subject.

13. The use according to claim 12, wherein the subject has one or more characteristics of the following <com:Math><semantics>(1)<annotation encoding="application / x-tex">(1)< / annotation>< / semantics>< / com:Math> to <com:Math><semantics>(5)<annotation encoding="application / x-tex">(5)< / annotation>< / semantics>< / com:Math>: (1) increased blood alanine aminotransferase (ALT) concentration compared to a control group not having nonalcoholic fatty liver disease, (2) increased blood aspartate aminotransferase (AST) concentration compared to the control group not having nonalcoholic fatty liver disease, (3) reduced secondary bile acid concentration in cecum compared to the control group not having nonalcoholic fatty liver disease, (4) increased fibrotic gene expression compared to the control group not having nonalcoholic fatty liver disease, and (5) increased ratio of liver weight to body weight compared to the control group not having nonalcoholic fatty liver disease. .

14. The use according to claim 12, wherein the subject has insulin resistance.

15. The use according to claim 12, wherein the subject has type 2 diabetes.