Polypeptide for use in the protection of oxygen sensitive gram-positive bacteria

Abstract

The invention concerns a Reg3α polypeptide (also known as Hepatocarcinoma-Intestine-Pancreas/Pancreatitis Associated Protein (HIP/PAP)) for protecting oxygen sensitive gram-positive bacteria, compositions comprising the polypeptide, and their use. The inventors showed that increasing concentration of the hReg3α lectin into the gastrointestinal tract (GIT) lumen of hReg3α-transgenic mice induced significant changes in composition of gut microbiota, and dramatically improved host resistance to intestinal inflammation. hReg3α exerted a potent antioxidant activity on intestinal epithelial cells during colitis, and the ROS scavenging activity, by promoting the survival of highly oxygen sensitive bacteria. Inventors also showed that hReg3α-transgenic mice were better able to resist DSS-induced colitis after antibiotherapy. The Reg3α polypeptide may be used for preventing or treating microbiota-related diseases and/or disorders, including inflammatory bowel disease (IBD), colitis, gastrointestinal infections, irritable bowel syndrome and other gastrointestinal functional diseases, gastrointestinal tract cancer, metabolic syndrome and obesity, diabetes, liver diseases, allergic diseases, neurodegenerative diseases and psychological disorders.

What is claimed is: 
     
         1 . A method for preventing or treating an imbalance of the microbiota comprising administering the Reg3α polypeptide comprising the amino acid sequence SEQ ID NO: 4 or a sequence at least 85% identical thereto to a host in need thereof. 
     
     
         2 . The method according to  claim 1 , wherein the imbalance of the microbiota is an imbalance of the gut microbiota. 
     
     
         3 . The method according to  claim 1 , wherein the imbalance of the microbiota is an imbalance of the gut microbiota induced by oxidative stress and/or an inflammatory response. 
     
     
         4 . The method according to  claim 1 , for preventing or treating a microbiota-related disease and/or disorder selected from the group consisting of inflammatory bowel disease (IBD), colitis, gastrointestinal infections, irritable bowel syndrome and other gastrointestinal functional diseases, allergic diseases and psychological disorders. 
     
     
         5 . The method according to  claim 1 , for preventing or treating the destruction of gut microbiota balance by medications, antibiotics, chemotherapy, radiotherapy, poor nutrition, eating disorders, illness, aging and/or genetics. 
     
     
         6 . The method according to  claim 1 , wherein the Reg3α polypeptide comprises the amino acid sequence SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO:3 or a sequence at least 85% identical thereto. 
     
     
         7 . The method according to  claim 1 , wherein the imbalance is characterized by a decreased proportion of immuno-protective Gram-positive bacteria. 
     
     
         8 . The method according to  claim 1 , wherein the Reg3α polypeptide protects oxygen sensitive gram-positive bacteria which are members of the Clostridiales order. 
     
     
         9 . The method according to  claim 8 , wherein the Reg3α polypeptide protects oxygen sensitive gram-positive bacteria belonging to the Ruminococcaceae family, such as  Faecalibacterium prausnitzii , and/or to the Lachnospiraceae family, such as  Roseburia intestinalis.    
     
     
         10 . The method according to  claim 1 , wherein the Reg3α polypeptide is in a pharmaceutical composition for oral or transmucosal administration in combination with at least one pharmaceutically acceptable excipient. 
     
     
         11 . A method for preventing or treating alterations or changes in composition and/or biodiversity of the gut microbiota comprising administering the Reg3α polypeptide comprising the amino acid sequence SEQ ID NO: 4 or a sequence at least 85% identical thereto to a host in need thereof. 
     
     
         12 . A method for protecting the beneficial symbionts of the gut microbiota of a host in need thereof, comprising administering the Reg3α polypeptide comprising the amino acid sequence SEQ ID NO: 4 or a sequence at least 85% identical thereto to a host in need thereof. 
     
     
         13 . A method for upregulating modulators of cell-matrix interactions and mucin O-glycosylation of the intestinal barrier in a host in need thereof, comprising administering the Reg3α polypeptide comprising the amino acid sequence SEQ ID NO: 4 or a sequence at least 85% identical thereto to the host in need thereof.