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CN-119875893-B - Isolated mucin-philin Acremonium, compositions containing same and uses

CN119875893BCN 119875893 BCN119875893 BCN 119875893BCN-119875893-B

Abstract

The invention provides isolated akkermansia muciniphila, a composition containing the same and application thereof, which can be used for treating, preventing or relieving obesity, metabolic disorder caused by obesity, diabetes, inflammation, liver and kidney diseases, liver diseases, cardiovascular and cerebrovascular diseases, tumors and the like.

Inventors

  • CHEN JUAN
  • HUANG BAOJIA
  • KONG PING

Assignees

  • 慕恩（广州）生物科技有限公司

Dates

Publication Date
20260505
Application Date
20241230
Priority Date
20240916

Claims (16)

  1. 1. An isolated akkermansia muciniphila (AKKERMANSIA MUCINIPHILA) which is a strain of akkermansia muciniphila MNH19250 deposited at the cantonese collection of microorganisms and cell cultures (GDMCC) under accession number GDMCC NO:63782 and a date of deposit of 2024, 6 and 21.
  2. 2. A composition comprising: a1 Achroman mucin-philic bacteria according to claim 1, or A2 A fermentation culture of Acremonium muciniphilum, or a dried product thereof, as defined in claim 1, or A3 A supernatant of Acremonium muciniphilum and its fermentation culture according to claim 1, or A4 Achroman mucin and its metabolites according to claim 1, or A5 The akkermansia muciniphila of claim 1 and proteins isolated from said akkermansia muciniphila.
  3. 3. The composition according to claim 2, The composition is a medicament.
  4. 4. The composition of claim 3, wherein the akkermansia muciniphila is a viable bacterium.
  5. 5. A composition according to claim 3, The colistin-philic ackermanni is freeze-dried.
  6. 6. The composition of any one of claims 2-5, comprising akkermansia muciniphila as an active ingredient, wherein the concentration of the akkermansia muciniphila is from 10 7 to 10 12 CFU/g.
  7. 7. The composition of claim 2-5, wherein the protein of Acremonium muciniphilum is Amuc-1100, and/or Amuc _1631.
  8. 8. The composition of any one of claims 2-5, further comprising one or more pharmaceutically acceptable carriers, excipients, and/or adjuvants.
  9. 9. The composition of any one of claims 2-5, further comprising one or more additional active agents for preventing or treating metabolic, cardiovascular, inflammatory and/or tumor diseases.
  10. 10. The composition of claim 9, wherein the additional active agent is one or more of a probiotic, a prebiotic, a GLP-1 receptor agonist.
  11. 11. The composition according to claim 10, The prebiotic is selected from inulin, mulberry leaf extract, berberine, ganoderma lucidum, green coffee bean extract, oat, pectin, potato or its extract, citrus polyphenols, cassiterite, ergothioneine, astaxanthin, quercetin, curcumin, procyanidins, resistant dextrin, ginseng or its extract, biotin, polydextrose, fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), starch, cellulose, b-glucan, hemicellulose, lactulose, mannooligosaccharides (MOS), gluco-oligosaccharides, tagatose, pectin, xylo-oligosaccharides (XOS), and/or any combination thereof The probiotics are at least one selected from lactobacillus, lactobacillus and butyric acid bacteria.
  12. 12. The composition according to claim 10, The prebiotic is selected from the group consisting of inulin rich in fructooligosaccharides, yeast beta-glucan, trans-galactooligosaccharides, resistant starch, and any combination thereof.
  13. 13. The composition of claim 2, which is a health product having at least one of the following functions: (1) Helping to control body fat; (2) Is helpful for maintaining blood lipid, cholesterol or triglyceride health level; (3) Is helpful for maintaining blood sugar health level.
  14. 14. Use of the akkermansia muciniphila of claim 1, or the composition of any one of claims 2-13, in the manufacture of a medicament for preventing, treating or alleviating a liver-kidney disease, a metabolic-related disease, a lipid-lowering, or an intestinal barrier-damage-related disease in a subject in need thereof; The liver and kidney diseases are selected from nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver (NAFLD), liver function abnormality caused by high fat diet, liver fibrosis caused by high fat diet, liver cell injury caused by high fat diet, kidney function abnormality caused by high fat diet, the metabolism related diseases are selected from obesity, diabetes, hyperglycemia, hypercholesterolemia, hyperlipidemia, metabolic syndrome caused by high fat diet, glucose intolerance caused by high fat diet, lipid metabolism abnormality caused by high fat diet, lipid abnormality caused by high fat diet, the intestinal barrier injury related diseases are selected from inflammatory bowel disease, crohn's disease, ulcerative colitis, the lipid reduction is selected from reducing visceral fat and/or local fat of obese individuals.
  15. 15. The use according to claim 14, wherein said akkermansia muciniphila or said composition reduces serum aspartate aminotransferase and/or alanyl aminotransferase ALT and/or liver weight in said subject and/or reduces the level of urea nitrogen BUN and/or creatinine CRE in serum of said subject and/or Said Acremonium muciniphilum, or said composition, increases colonic mucus layer thickness, and/or The Achroman muciniphila or the composition has at least one characteristic selected from the group consisting of regulating metabolism while regulating immunity, reducing abdominal fat while repairing intestinal barrier damage, reducing liver damage while reducing weight, reducing weight while resisting inflammation, reducing blood lipid while repairing intestinal barrier damage, reducing serum AST and/or ALT while reducing blood lipid, improving liver damage while improving kidney damage, improving diabetes while improving liver damage, and improving kidney damage while improving diabetes.
  16. 16. The use of claim 15, wherein said akkermansia muciniphila or said composition is capable of treating, preventing, alleviating or ameliorating at least one of the following: (1) Weight loss or weight control; (2) Preventing, treating, improving or alleviating liver injury caused by NAFLD or NASH, high fat diet; (3) Preventing, treating, improving or relieving renal injury and renal dysfunction caused by high fat diet; (4) Promoting the expression of IFN beta of the type I interferon of the subject, and improving the immunity; (5) Preventing, treating, ameliorating or alleviating diabetes; (6) Lowering blood lipid and/or cholesterol levels in a subject; (7) Reducing local fat, body fat rate, and/or visceral fat in a subject; (8) Repairing intestinal tissue mucosa of a subject.

Description

Isolated mucin-philin Acremonium, compositions containing same and uses Technical Field The present disclosure relates to the field of microorganisms, more particularly to novel strains of isolated mucin-philin ackerman species, compositions comprising the same and uses thereof. Background Achroman mucin (AKKERMANSIA MUCINIPHILA) is a mucin-decomposing bacterium that generally colonizes the intestinal tract of humans and many animals. The screening of new strains of Achroman mucin is very difficult because they are mainly found in the human or animal intestinal tract, belong to strictly anaerobic microorganisms, have extremely high requirements on nutrition and culture environment, and have a long growth cycle. In addition, the bacteria of the genus are difficult to verify by in vitro cell experiments because of anaerobism, and the bacteria of the genus are difficult to maintain stable viable cell count and have insufficient reproducibility because of difficulty in culture and high anaerobic degree in the in vivo animal experiment process. These in vitro and in vivo related technical difficulties limit the discovery and application of new strains of akkermansia muciniphila. In addition, acremonium muciniphilum grows slowly and is difficult to compete with other microbial strains, so that the problem of difficult availability in the screening process exists. The AKKPROBIO strain disclosed in CN116925975B has hydrophobicity reaching 31% at 60min, and self-aggregation property tends to be stable at 20h and is kept at about 52%. It is believed that AKKPROBIO has a weak biofilm formation capacity, and in vitro test results show that AKKPROBIO has a low colonization capacity in the intestinal tract (https:// doi.org/10.3390/foods13030442, section 3.1). AKK strains have limited their commercial exploitation if they have poor colonisation adhesion. The prevalence of metabolic diseases such as obesity, diabetes, hypertension, hyperlipidemia, fatty liver and the like is increasing, and studies have also shown that these diseases are associated with dysbiosis of microbial flora. Achroman mucin is inversely related to obesity, diabetes, cardiovascular disease, and low-grade inflammation in many populations. Acremonium muciniphilum can protect the integrity of intestinal epithelial cells and mucus layers, thereby playing a role in metabolism protection. Mixtures of various microorganisms are commonly used in the art for the treatment of metabolic and obesity related diseases or disorders, such as probiotics or intestinal flora transplants (FMT). However, the mechanism is further complicated by a mixture of microorganisms, the interactions between the microorganisms have not been well studied, and the use of a mixture of microorganisms often breaks the homeostasis of the intestinal flora. Furthermore, the use of a mixture of microorganisms requires additional consideration of whether the individual microorganisms affect each other's activity, nor is it clear whether the synergistic effect of the mixture of microorganisms makes it useful in the treatment or prevention of a disease or whether a single species of bacteria plays a role in the treatment or prevention of a disease. The number of microbial sources is extremely large, and the selection of new species or strains from which to select for effective use in the treatment or prevention of diseases such as obesity, diabetes, hypertension, hyperlipidemia, liver and kidney function diseases, tumors, etc., is a great challenge, but represents a great unmet need. Disclosure of Invention The present disclosure isolated a novel mucin-philin ackerman strain (AKKERMANSIA MUCINIPHILA). Compared with the existing mucin-philin Ackerman strain, the novel strain has stronger epithelial cell adhesion capability, can be well colonized in the intestinal tract of a human body or an animal, can prolong the stay time in the intestinal tract, can better exert the drug effect in the intestinal tract, and can effectively prevent pathogenic bacteria from adhering due to the excellent colonization adhesion capability of the strain, thereby being beneficial to maintaining the stable state and health of the intestinal tract. In addition, the strain disclosed by the invention can synthesize a large amount of short chain fatty acids, thereby effectively playing a role in treating or preventing metabolic diseases, reducing the body weight, body fat, blood sugar, blood fat and cholesterol of a subject, improving or reducing the effects of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) and repairing intestinal tissue mucous membranes, and promoting the expression of IFN beta of type I interferon of the subject and improving the immunity, so that the strain has the potential of preventing or treating viral infection and inhibiting tumor growth. In a first aspect, the present disclosure provides an isolated akkermansia muciniphila (AKKERMANSIA MUCINIPHILA) having an A