Use of a polypeptide for effecting immune signalling and/or affecting intestinal barrier function and/or modulating metabolic status
It has been found that an extracellular polypeptide derived from Akkermansia municiphila is capable of modulating and/or promoting gut mucosal immune system function and/or maintaining and/or restoring metabolic status and/or increasing the physical integrity of the gut mucosal barrier in a mammal. The polypeptide or host cells including such polypeptide may be employed to prevent and/or treat a variety of conditions that benefit from an increased physical integrity of the gut mucosal barrier and/or an improved gut mucosal immune system function and metabolic status.
1. A method for treating a disease or disorder associated with an impaired gut barrier or immune cell function in a subject in need thereof, comprising
administering to the subject an effective amount of an isolated polypeptide having at least 90% identity to the amino acid sequence of SEQ ID NO:1 over the entire length of SEQ ID NO:1,
thereby treating the subject of the disease or disorder.
2. The method of claim 1 , wherein the isolated polypeptide comprises the amino acid sequence set forth in SEQ ID NO:1.
3. The method of claim 1 , wherein the disease or disorder is:
a metabolic condition selected from the group consisting of: obesity; metabolic syndrome; insulin-deficiency; insulin-resistance related disorders; type 2 diabetes; type 1 diabetes; gestational diabetes; glucose intolerance; abnormal lipid metabolism; hyperglycemia; dyslipidemias; obesity; high cholesterol; and elevated triglycerides;
an inflammatory or immune condition selected from the group consisting of: inflammatory bowel disease (IBD); irritable bowel syndrome (IBS); non-alcoholic fatty liver disease; alcoholic fatty liver disease; hepatic steatosis; gallbladder disease; allergy; asthma; osteoarthritis; and cancer;
a vascular or cardiovascular condition selected from the group consisting of: preeclampsia; atherosclerosis; cardiovascular disease; cardiac pathology; hypertension; stroke; and wound healing; or
a behavioral or neurological condition selected from the group consisting of: autism; Parkinson's disease; multiple sclerosis; neurodegenerative disease; depression; alcohol dependence; and sleep apnea.
4. The method of claim 1 , wherein the impaired gut barrier function is a result of one or more causes selected from the group consisting of: food allergies; premature birth; immaturity of the gut; radiation; chemotherapy; toxins, autoimmune disorders; malnutrition; and sepsis.
5. The method of claim 1 , wherein administering an effective amount of the polypeptide maintains, restores, and/or increases the physical integrity of the mucosal gut barrier and/or improves the gut mucosal immune system function of the subject.
6. The method of claim 1 , wherein administering an effective amount of a polypeptide improves glucose, cholesterol, and/or triglyceride homeostasis, and/or promotes weight loss in the subject.
7. The method of claim 1 , wherein the polypeptide is administered orally, intravenously, topically, enterally, or parenterally.
8. The method of claim 1 , wherein the polypeptide is isolated from an Akkermansia bacterial species.
9. The method of claim 1 , wherein the polypeptide is isolated from Akkermansia muciniphila.
10. A method for treating a disease or disorder associated with impaired gut barrier or immune cell function in a subject in need thereof, comprising
administering to the subject a genetically modified isolated host cell comprising a nucleic acid molecule encoding an isolated polypeptide having at least 90% identity to the amino acid sequence of SEQ ID NO:1 over the entire length of SEQ ID NO:1,
thereby treating the subject of the disease or disorder.
11. The method of claim 10 , wherein the isolated polypeptide comprises the amino acid sequence set forth in SEQ ID NO:1, or wherein the isolated polypeptide comprises the nucleic acid sequence set forth in SEQ ID NO:2.
12. The method of claim 10 , wherein the disease or disorder is:
a metabolic condition selected from the group consisting of: obesity; metabolic syndrome; insulin-deficiency; insulin-resistance related disorders; type 2 diabetes; type 1 diabetes; gestational diabetes; glucose intolerance; abnormal lipid metabolism; hyperglycemia; dyslipidemias; obesity; high cholesterol; and elevated triglycerides;
an inflammatory or immune condition selected from the group consisting of: inflammatory bowel disease (IBD); irritable bowel syndrome (IBS); non-alcoholic fatty liver disease; alcoholic fatty liver disease; hepatic steatosis; gallbladder disease; allergy; asthma; osteoarthritis; and cancer;
a vascular or cardiovascular condition selected from the group consisting of: preeclampsia; atherosclerosis; cardiovascular disease; cardiac pathology; hypertension; stroke; and wound healing; or
a behavioral or neurological condition selected from the group consisting of: autism; Parkinson's disease; multiple sclerosis; neurodegenerative disease; depression; alcohol dependence; and sleep apnea.
13. The method of claim 10 , wherein the impaired gut barrier function is a result of one or more causes selected from the group consisting of: food allergies; premature birth; immaturity of the gut; radiation; chemotherapy; toxins, autoimmune disorders; malnutrition; and sepsis.
14. The method of claim 10 , wherein administering the genetically altered host cell maintains, restores, and/or increases the physical integrity of the mucosal gut barrier and/or improves the gut mucosal immune system function of the subject.
15. The method of claim 10 , wherein administering the genetically altered host cell improves glucose, cholesterol, and/or triglyceride homeostasis, and/or promotes weight loss in the subject.
16. The method of claim 10 , wherein the polypeptide is isolated from an Akkermansia bacterial species.
17. The method of claim 10 , wherein the polypeptide is isolated from Akkermansia muciniphila.
18. A method for treating a disease or disorder associated with impaired gut barrier or immune cell function in a subject in need thereof, comprising
administering to the subject an effective amount of a pharmaceutical composition comprising an isolated polypeptide having at least 90% identity to the amino acid sequence of SEQ ID NO:1 over the entire length of SEQ ID NO:1,
thereby treating the subject of the disease or disorder.
19. The method of claim 18 , wherein the isolated polypeptide comprises the amino acid sequence set forth in SEQ ID NO:1.
20. The method of claim 18 , wherein the disease or disorder is:
a metabolic condition selected from the group consisting of: obesity; metabolic syndrome; insulin-deficiency; insulin-resistance related disorders; type 2 diabetes; type 1 diabetes; gestational diabetes; glucose intolerance; abnormal lipid metabolism; hyperglycemia; dyslipidemias; obesity; high cholesterol; and elevated triglycerides;
an inflammatory or immune condition selected from the group consisting of: inflammatory bowel disease (IBD); irritable bowel syndrome (IBS); non-alcoholic fatty liver disease; alcoholic fatty liver disease; hepatic steatosis; gallbladder disease; allergy; asthma; osteoarthritis; and cancer;
a vascular or cardiovascular condition selected from the group consisting of: preeclampsia; atherosclerosis; cardiovascular disease; cardiac pathology; hypertension; stroke; and wound healing; or
a behavioral or neurological condition selected from the group consisting of: autism; Parkinson's disease; multiple sclerosis; neurodegenerative disease; depression; alcohol dependence; and sleep apnea.
21. The method of claim 18 , wherein the impaired gut barrier function is a result of one or more causes selected from the group consisting of: food allergies; premature birth; immaturity of the gut; radiation; chemotherapy; toxins, autoimmune disorders; malnutrition; and sepsis.
22. The method of claim 18 , wherein administering an effective amount of the pharmaceutical composition maintains, restores, and/or increases the physical integrity of the mucosal gut barrier and/or improves the gut mucosal immune system function of the subject.
23. The method of claim 18 , wherein administering an effective amount of the pharmaceutical composition improves glucose, cholesterol, and/or triglyceride homeostasis, and/or promotes weight loss in the subject.
24. The method of claim 18 , wherein the pharmaceutical composition is administered orally, intravenously, topically, enterally, or parenterally.
25. The method of claim 18 , wherein the polypeptide is isolated from an Akkermansia bacterial species.
26. The method of claim 18 , wherein the polypeptide is isolated from Akkermansia municiphila.