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WO2025225801A1 - Souche de clostridium butyricum dérivée du microbiome coréen ayant une efficacité anti-obésité, et son utilisation - Google Patents

Souche de clostridium butyricum dérivée du microbiome coréen ayant une efficacité anti-obésité, et son utilisation

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Publication number
WO2025225801A1
WO2025225801A1 PCT/KR2024/017253 KR2024017253W WO2025225801A1 WO 2025225801 A1 WO2025225801 A1 WO 2025225801A1 KR 2024017253 W KR2024017253 W KR 2024017253W WO 2025225801 A1 WO2025225801 A1 WO 2025225801A1
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WIPO (PCT)
Prior art keywords
strain
clostridium butyricum
obesity
disease
metabolic disease
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Pending
Application number
PCT/KR2024/017253
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English (en)
Korean (ko)
Inventor
이종수
장영효
바이루
백자영
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Korea Research Institute of Bioscience and Biotechnology KRIBB
Industry and Academy Cooperation In Chungnam National University
Original Assignee
Korea Research Institute of Bioscience and Biotechnology KRIBB
Industry and Academy Cooperation In Chungnam National University
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Application filed by Korea Research Institute of Bioscience and Biotechnology KRIBB, Industry and Academy Cooperation In Chungnam National University filed Critical Korea Research Institute of Bioscience and Biotechnology KRIBB
Publication of WO2025225801A1 publication Critical patent/WO2025225801A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
    • A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/145—Clostridium

Definitions

  • the present invention relates to a Clostridium butyricum strain derived from a Korean microbiome having anti-obesity efficacy and its use.
  • Obesity is a condition characterized by excessive accumulation of fat tissue in the body. It is primarily caused by an energy imbalance, resulting from excessive nutrient intake relative to energy expenditure. It is also known to be induced by hormonal changes, genetics, mental health issues, and socioeconomic factors. The number of obese people is increasing worldwide, and obesity has recently been identified as a significant risk factor for adult diseases, making the severity of obesity a significant issue.
  • fenfluramine which inhibits the serotonergic nervous system
  • ephedrine and caffeine which act through the noradrenergic nervous system
  • sibutramine which acts simultaneously on both serotonergic and noradrenergic nervous systems
  • orlistat which inhibits pancreatic lipase to reduce fat absorption.
  • existing medications such as fenfluramine
  • fenfluramine have been banned due to side effects such as primary pulmonary hypertension and heart valve disease.
  • Other medications also cause hypotension and lactic acidosis, making them unsuitable for patients with heart failure or renal disease. Therefore, the development of substances for the prevention, improvement, or treatment of obesity with fewer side effects is urgently needed.
  • Korean Patent No. 2183841 discloses 'a novel Lactobacillus plantarum Ln4 strain and a pharmaceutical composition for preventing and treating obesity containing the same'
  • Korean Patent No. 1508586 discloses 'a novel Enterococcus ficalis MD366 strain with excellent anti-obesity activity', but the Korean microbiome-derived Clostridium butyricum strain with anti-obesity activity of the present invention and its use are not described.
  • the present invention was derived from the above-mentioned needs, and the inventors of the present invention confirmed that the Clostridium butyricum S-45-5 strain, deposited number KCTC12754BP, has an excellent effect of reducing body weight and adipose tissue weight of experimental animals under high-fat diet conditions compared to the control group (untreated strain), and has an excellent effect of reducing the contents of total cholesterol, triglycerides, LDL (low-density lipoprotein), leptin, ALT (alanine aminotransferase), and AST (aspartate aminotransferase) in the serum, and has an excellent effect of reducing blood sugar and increasing GLP-1 (glucagon-like peptide-1) contents in an oral glucose tolerance test.
  • the present invention was completed by confirming that the anti-obesity activity of the Clostridium butyricum S-45-5 strain of the present invention is superior to that of other strains of the same genus and species.
  • the present invention provides a pharmaceutical composition for preventing or treating obesity or metabolic disease, which contains Clostridium butyricum S-45-5 strain having a deposit number of KCTC12754BP or a culture solution thereof as an active ingredient.
  • the present invention provides a health functional food composition for preventing or improving obesity or metabolic disease, which contains Clostridium butyricum S-45-5 strain having a deposit number of KCTC12754BP or a culture solution thereof as an active ingredient.
  • the present invention provides a feed additive for improving obesity or metabolic disease, which contains Clostridium butyricum S-45-5 strain having a deposit number of KCTC12754BP or a culture solution thereof as an active ingredient.
  • the present invention provides a veterinary composition for preventing or treating obesity or metabolic disease, which comprises Clostridium butyricum S-45-5 strain having a deposit number of KCTC12754BP or a culture solution thereof as an active ingredient.
  • Clostridium butyricum S-45-5 strain of the present invention has excellent anti-obesity activity, it is expected that it can be usefully utilized as a material for a composition for preventing, improving, or treating obesity and metabolic diseases caused by obesity.
  • Figure 1 shows the results of body weight measurement for 12 weeks after oral administration of Clostridium butyricum S-45-5 strain to a high-fat diet animal model.
  • ND normal diet
  • HFD high-fat diet.
  • Figure 2 shows the results of measuring the contents of total cholesterol (T-chol), triglyceride (TG), low-density cholesterol (LDL-C), and high-density cholesterol (HDL-C) by isolating serum after oral administration of Clostridium butyricum S-45-5 strain to a high-fat diet animal model.
  • T-chol total cholesterol
  • TG triglyceride
  • LDL-C low-density cholesterol
  • HDL-C high-density cholesterol
  • Figure 3 shows the results of separating epididymal fat and perirenal fat after oral administration of Clostridium butyricum S-45-5 strain to a high-fat diet animal model, performing H&E (hematoxylin and eosin) staining, measuring the weight of each fat, and separating serum to measure the content of leptin.
  • H&E hematoxylin and eosin
  • Figure 4 shows the results of orally administering Clostridium butyricum S-45-5 strain to a high-fat diet animal model, isolating the liver, performing H&E staining, measuring the weight of the liver, and isolating the serum to measure the contents of ALT (alanine aminotransferase) and AST (aspartate aminotransferase).
  • Figure 5 shows the results of administering Clostridium butyricum S-45-5 strain orally to a high-fat diet animal model, administering glucose orally at week 8, fasting for 2 hours, collecting blood through the tail vein to measure blood sugar, islet of Langerhans isolation and performing H&E staining, measuring the content of GLP-1 (glucagon-like peptide-1), and measuring feed intake.
  • Figure 6 shows the results of measuring body weight for 12 weeks after orally administering Clostridium butyricum S-45-5 strain, Clostridium butyricum Miyairi strain, or Clostridium butyricum strain (KCTC 1871) to a high-fat diet animal model.
  • Figure 7 shows the results of measuring the contents of total cholesterol (T-chol), triglyceride (TG), low-density cholesterol (LDL-C), and high-density cholesterol (HDL-C) in serum after oral administration of Clostridium butyricum S-45-5 strain, Clostridium butyricum Miyairi strain, or Clostridium butyricum strain (KCTC 1871) to a high-fat diet animal model.
  • T-chol total cholesterol
  • TG triglyceride
  • LDL-C low-density cholesterol
  • HDL-C high-density cholesterol
  • Figure 8 shows the results of separating the fat around the epididymis and the fat around the kidney, performing H&E staining, measuring the weight of each fat, and separating the serum to measure the leptin content after orally administering Clostridium butyricum S-45-5 strain, Clostridium butyricum Miyairi strain, or Clostridium butyricum strain (KCTC 1871) to a high-fat diet animal model.
  • Figure 9 shows the results of orally administering Clostridium butyricum S-45-5 strain, Clostridium butyricum Miyairi strain, or Clostridium butyricum strain (KCTC 1871) to a high-fat diet animal model, isolating the liver, performing H&E staining, measuring the weight of the liver, and isolating the serum to measure the contents of ALT and AST.
  • Figure 10 shows a taxonomic phylogenetic tree of the Clostridium butyricum S-45-5 strain of the present invention.
  • the present invention provides a pharmaceutical composition for preventing or treating obesity or metabolic disease, which contains Clostridium butyricum S-45-5 strain having a deposit number of KCTC12754BP or a culture solution thereof as an active ingredient.
  • the metabolic disease refers to diabetes, hyperlipidemia or non-alcoholic fatty liver disease caused by obesity
  • the non-alcoholic fatty liver disease may be any one selected from the group consisting of obesity-induced fatty liver disease, diabetic fatty liver disease, steatohepatitis, simple fatty liver disease, nutritional fatty liver disease, starvation-induced fatty liver disease, liver fibrosis and liver cirrhosis, but is not limited thereto.
  • the Clostridium butyricum S-45-5 strain having the deposit number KCTC12754BP is characterized by an excellent effect in reducing body weight and adipose tissue weight of experimental animals compared to the control group (untreated strain) under high-fat diet conditions, an excellent effect in reducing the contents of total cholesterol, triglycerides, LDL (low-density lipoprotein), leptin, ALT (alanine aminotransferase), and AST (aspartate aminotransferase) in serum, and an excellent effect in reducing blood sugar and increasing GLP-1 (glucagon-like peptide-1) contents in an oral glucose tolerance test.
  • Clostridium butyricum S-45-5 strain with the above-mentioned accession number KCTC12754BP is characterized by its lack of bile salt decomposition ability and hemolysis.
  • the method for culturing the Clostridium butyricum S-45-5 strain of the present invention can be performed according to a method commonly used in the art, and is not limited to a specific method.
  • the strain culture means the strain cultured in a culture medium, and may include both a concentrate of the culture or a dried product thereof.
  • the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent in addition to the above-mentioned effective ingredient, and may be in various oral or parenteral dosage forms.
  • a pharmaceutically acceptable carrier such as commonly used fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants.
  • Solid preparations for oral administration include capsules, powders, granules, tablets, pills, etc., and these solid preparations are prepared by mixing one or more compounds with at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc.
  • Liquid preparations for oral administration include suspensions, emulsions, syrups, and aerosols.
  • simple diluents such as water and liquid lapine
  • various excipients such as wetting agents, sweeteners, flavoring agents, and preservatives, may be included.
  • Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories.
  • Non-aqueous solvents and suspending agents can be propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
  • Suppository bases can be witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin.
  • a method such as topical application to the skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine, epidural, or intracerebrovascular injection.
  • composition according to the present invention is administered in a pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment.
  • the level of the effective amount may be determined based on factors including the type and severity of the patient's disease, the activity and sensitivity of the drug to the drug, the time of administration, the route of administration and excretion rate, the duration of treatment, concurrently used drugs, and other factors well known in the medical field.
  • the composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or in multiple doses. It is important to take all of the above factors into consideration and administer an amount that achieves the maximum effect with the minimum amount without causing side effects, and this can be easily determined by those skilled in the art.
  • the present invention also provides a health functional food composition for preventing or improving obesity or metabolic disease, containing Clostridium butyricum S-45-5 strain having a deposit number of KCTC12754BP or a culture solution thereof as an active ingredient.
  • the metabolic disease is as described above.
  • the health functional food composition of the present invention is preferably manufactured in any one dosage form selected from powder, granules, pills, tablets, capsules, candy, syrup, and beverage, but is not limited thereto.
  • the health functional food composition of the present invention may be manufactured by adding the active ingredient as it is or mixing it with other foods or food ingredients, and may be manufactured appropriately according to a conventional method.
  • foods to which the above-mentioned active ingredient can be added include dairy products including caramel, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and include all health functional foods in the conventional sense.
  • the above health functional food composition may contain various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavorings, colorings and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.
  • it may contain fruit pulp for producing natural fruit juice and vegetable beverages.
  • the above ingredients may be used independently or in combination.
  • the health functional food composition of the present invention may contain various flavorings or natural carbohydrates as additional ingredients, and the natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol.
  • the ratio of the above natural carbohydrates is not particularly important, but is preferably 0.01 to 0.04 g, more preferably 0.02 to 0.03 g, per 100 g of the composition of the present invention, but is not limited thereto.
  • natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame can be used.
  • the present invention also provides a feed additive for improving obesity or metabolic disease, which comprises Clostridium butyricum S-45-5 strain having a deposit number of KCTC12754BP or a culture solution thereof as an active ingredient.
  • the feed additive of the present invention corresponds to supplementary feed under the Feed Management Act.
  • the term 'feed' in the present invention may mean any natural or artificial diet, meal, etc., or ingredients of the meal, which are suitable for or intended for animals to eat, ingest, and digest.
  • the type of the feed is not particularly limited, and feed commonly used in the relevant technical field may be used.
  • Non-limiting examples of the feed include plant feeds such as grains, roots, fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal, or grain by-products; and animal feeds such as proteins, inorganic substances, oils and fats, mineral substances, oils and fats, single-cell proteins, zooplankton, or food. These may be used alone or in combination of two or more.
  • the present invention also provides a veterinary composition for preventing or treating obesity or metabolic disease, comprising Clostridium butyricum S-45-5 strain having a deposit number of KCTC12754BP or a culture solution thereof as an active ingredient.
  • the veterinary composition of the present invention may further comprise suitable excipients and diluents according to conventional methods.
  • Excipients and diluents that may be included in the veterinary composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, cetanol, stearyl alcohol, liquid paraffin, sorbitan monostearate, polysorbate 60, methylparaben, propylparaben, and mineral oil.
  • the veterinary composition according to the present invention may further include fillers, anticoagulants, lubricants, wetting agents, flavorings, emulsifiers, preservatives, etc., and the veterinary composition according to the present invention may be formulated using a method well known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to an animal, and the formulation may be in the form of powders, granules, tablets, capsules, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, suppositories, sterile injectable solutions, sterile topical preparations, etc.
  • the effective amount of the veterinary composition according to the present invention may be appropriately selected depending on the individual animal.
  • Clostridium butyricum S-45-5 strain (KCTC 12754BP), Clostridium butyricum Miyairi strain (CBM588), or Clostridium butyricum strain (KCTC 1871) was used in the experiment.
  • Each strain was cultured in PYG (Peptone Yeast Glucose) liquid medium at 37°C for 48 hours, and the culture solution was centrifuged at 4,000 rpm at 4°C for 20 minutes to obtain a pellet. The pellet was washed three times with PBS (phosphate buffered saline), and then diluted to the desired concentration with PBS for use in the experiment.
  • PYG Peptone Yeast Glucose
  • mice Four-week-old C57/BL6J mice were acclimated to constant conditions (temperature: 22 ⁇ 2°C, humidity: 50 ⁇ 5%, light/dark cycle: 12 hours) in an animal breeding room for one week, and then randomly divided into groups of 10 mice each according to Table 1 below for the experiment. Each group was fed a normal diet (ND) or a high-fat diet (HFD), and PBS or each strain was administered orally daily for 12 weeks (Fig. 1A and Fig. 6A). Body weight was measured daily, and after the experiment, serum, liver tissue, and adipose tissue were extracted and used in subsequent experiments. After the first experiment to analyze the anti-obesity activity of Clostridium butyricum S-45-5 strain, the second experiment was performed to compare the anti-obesity activity of each Clostridium butyricum strain.
  • ND normal diet
  • HFD high-fat diet
  • a taxonomic phylogenetic tree based on 100 core genes was generated using AutoMLST based on whole-genome sequences of genetically homologous related strains, and maximum-likelihood phylogenetic analysis was performed using IQ-tree. Average nucleotide identity (ANI) values were calculated using an ANI calculator, and digital DNA-DNA hybridization (dDDH) was estimated using a genome-to-genome homology calculator. In addition, whole-genome sequences of strains, along with their respective GenBank numbers, were used to perform ANI, dDDH, and species phylogenetic analyses.
  • ANI nucleotide identity
  • dDDH digital DNA-DNA hybridization
  • Bile salt degradation was evaluated using a plate assay.
  • the medium used for the analysis was prepared by adding 1 mM sodium salts of taurocholic acid (TCA), glycocholic acid (GCA), taurodeoxycholic acid (TDCA), and taurodeoxycholic acid (TCDCA) to Reinforced Clostridial Medium (RCM).
  • TCA taurocholic acid
  • GCA glycocholic acid
  • TDCA taurodeoxycholic acid
  • TCDCA taurodeoxycholic acid
  • Hemolytic assay was performed by culturing Clostridium butyricum S-45-5 strain and Clostridium butyricum Miyairi strain in RCM medium containing blood at 37°C for 48 hours, and analyzing blood hemolytic reaction according to the type of ring formed around the colony.
  • Clostridium butyricum S-45-5 strain was analyzed in a high-fat diet animal model.
  • the normal group was fed a normal diet instead of a high-fat diet, and the control group was fed a high-fat diet and orally administered PBS instead of the strain.
  • a high-fat diet animal model was orally administered 2x108 CFU or 5x108 CFU of Clostridium butyricum S-45-5 strain for 12 weeks, and body weight was measured daily.
  • Dyslipidemia is a condition in which the levels of total cholesterol, low-density cholesterol, and triglycerides in the blood increase or the levels of high-density cholesterol decrease, and is known to be caused by obesity, diabetes, etc.
  • Clostridium butyricum S-45-5 strain was excellent in reducing blood lipid content.
  • ALT alanine aminotransferase
  • AST aspartate aminotransferase
  • the liver weight and ALT and AST contents of the control group increased compared to the normal group, whereas the liver weight and ALT and AST contents of the Clostridium butyricum S-45-5 strain administration group decreased compared to the control group.
  • the control group formed a large number of lipid droplets in the liver tissue, whereas the normal group and the Clostridium butyricum S-45-5 strain administration group did not form lipid droplets in the liver tissue (Fig. 4).
  • the islets of Langerhans are clusters of cells that are responsible for the exocrine function of the pancreas, and they secrete hormones such as insulin and glucagon to regulate blood sugar levels.
  • GLP-1 is a substance secreted in the small intestine that increases insulin secretion depending on glucose concentration, and is attracting attention as a new candidate drug for the treatment of diabetes.
  • 2x108 CFU or 5x108 CFU of Clostridium butyricum S-45-5 strain was orally administered daily, and at week 8, glucose was orally administered at 2 g/kg, and after fasting for 2 hours, blood was collected through the tail vein to measure blood glucose, islets of Langerhans were isolated and stained with H&E, the content of GLP-1 was measured, and daily feed intake was measured.
  • the anti-obesity activity of the Clostridium butyricum S-45-5 strain which was confirmed to have anti-obesity activity in Example 1, was analyzed by comparing it with the Clostridium butyricum Miyairi strain or the Clostridium butyricum strain (KCTC 1871).
  • 5x10 8 CFU of Clostridium butyricum S-45-5 strain 5x10 8 CFU of Clostridium butyricum Miyairi strain, or 5x10 8 CFU of Clostridium butyricum strain (KCTC 1871) were orally administered for 12 weeks, and body weight was measured daily.
  • 5x108 CFU of Clostridium butyricum S-45-5 strain 5x108 CFU of Clostridium butyricum Miyairi strain
  • 5x108 CFU of Clostridium butyricum strain KCTC 1871
  • H&E hematoxylin and eosin
  • the liver weight and ALT and AST contents of the Clostridium butyricum S-45-5 strain administration group were lower than those of the Clostridium butyricum Miyairi strain or the Clostridium butyricum strain (KCTC 1871) administration group.
  • the formation of lipid droplets in the liver tissue of the Clostridium butyricum S-45-5 strain administration group was suppressed more than those of the Clostridium butyricum Miyairi strain or the Clostridium butyricum strain (KCTC 1871) administration group (Fig. 9).
  • Clostridium butyricum S-45-5 strain showed the highest sequence homology of 99.1% with the Clostridium butyricum DSM 10702T strain (Fig. 10).
  • the ANI values of the Clostridium butyricum S-45-5 strain and related strains ranged from 76.6 to 99.1%, and the dDDH values ranged from 20.4 to 91.8% (Table 2).
  • the Clostridium butyricum S-45-5 strain of the present invention belongs to the Butyricum species within the genus Clostridium.
  • Clostridium butyricum S-45-5 strain and Clostridium butyricum MIYAIRI strain were confirmed to have no ability to decompose taurocholic acid (TCA), glycocholic acid (GCA), taurodeoxycholic acid (TDCA), and taurodeoxycholic acid (TCDCA), and were also confirmed to have no hemolysis (Table 3).
  • Bile salt decomposition and hemolytic activity assay Clostridium butyricum S-45-5 Clostridium butyricum MIYAIRI Bile salt decomposition capacity TCA - - TCDCA - - TDCA - - GCA - - hemolytic - -

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Abstract

La présente invention concerne une souche de Clostridium butyricum dérivée du microbiome coréen ayant une efficacité anti-obésité, et son utilisation. La souche a un excellent effet de réduction du poids corporel et du poids du tissu adipeux chez les animaux expérimentaux par rapport à un groupe témoin (non traité par la souche) dans des conditions de régime riche en graisse, a un excellent effet de réduction de la teneur en cholestérol total, en triglycérides, en lipoprotéine basse densité (LDL), en leptine, en alanine aminotransférase (ALT) et en aspartate aminotransférase (AST) dans le sérum, et a un excellent effet de réduction de la glycémie et d'augmentation de la teneur en peptide-1 de type glucagon (GLP-1) dans un test de charge de glucose oral ; ainsi, il est attendu que la souche soit utile en tant qu'ingrédient dans une composition pour prévenir, atténuer ou traiter l'obésité et les maladies métaboliques provoquées par l'obésité.
PCT/KR2024/017253 2024-04-24 2024-11-05 Souche de clostridium butyricum dérivée du microbiome coréen ayant une efficacité anti-obésité, et son utilisation Pending WO2025225801A1 (fr)

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KR1020240054618A KR102679094B1 (ko) 2024-04-24 2024-04-24 항비만 효능을 지닌 한국인 마이크로바이옴 유래 클로스트리디움 부티리쿰 균주 및 이의 용도
KR10-2024-0054618 2024-04-24

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KR102853868B1 (ko) * 2025-01-10 2025-09-03 서무경 혈당스파이크 완화 및 식욕억제 효과가 탁월한 신규 낙산균(clostridium butyricum) YS11365 균주 및 이의 용도
CN119950558A (zh) * 2025-02-26 2025-05-09 南昌大学 丁酸梭菌ncu-02在制备改善高脂血症和/或自闭症药物的应用

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KR101773059B1 (ko) * 2015-03-26 2017-08-31 한국생명공학연구원 면역 증진 및 항바이러스 활성을 가지는 클로스트리디움 부티리쿰 균주 및 이의 용도
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