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

Patent metadata

Field	Value
Publication number	US-11484569-B2
Application number	US-201816630252-A
Country	US
Kind code	B2
Filing date	Jul 13, 2018
Priority date	Jul 13, 2017
Publication date	Nov 1, 2022
Grant date	Nov 1, 2022

Abstract

The invention concerns a Reg3α polypeptide (also known as Hepatocarcinoma-Intestine-Pancreas/Pancreatitis Associated Protein (HIP/PAP)) for use in the protection of oxygen sensitive gram-positive bacteria, compositions comprising the polypeptide and their use. The inventors have shown that an increase in the concentration of the h Reg3α lectin into the gastrointestinal tract (GIT) lumen of hReg3α-transgenic mice induced significant changes in the composition of the gut microbiota, and dramatically improved host resistance to intestinal inflammation. hReg3α exerted a potent antioxidant activity on intestinal epithelial cells during colitis, and in particular the ROS scavenging activity, in particular, by promoting the survival of highly oxygen sensitive bacteria. Inventors also showed that h Reg3α-transgenic mice resist better to DSS-induced colitis after antibiotherapy. Thus, the invention concerns a Reg3α polypeptide for use in the protection of oxygen sensitive gram-positive bacteria, notably the Ruminococcaceae, such as Faecalibacterium prausnitzii, and/or the Lachnospiraceae, such as Roseburia intestinalis; pharmaceutical compositions comprising the polypeptide and their use; and the use of this polypeptide for promoting ex vivo growth of oxygen sensitive gram-positive bacteria. The Reg3α polypeptide may be used for preventing or treating microbiota-related disease and/or disorder, particularly selected from 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.

First claim

The invention claimed is:

1. A method for promoting ex vivo growth of oxygen sensitive gram-positive bacteria comprising contacting said bacteria with a Reg3α polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4.

2. The method according to claim 1 , wherein the oxygen sensitive bacteria are members of the Clostridiales order.

3. The method according to claim 1 wherein the polypeptide comprises the amino acid sequence SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO:3.

4. The method according to claim 1 wherein the gram-positive bacteria belong to the Ruminococcaceae and/or to the Lachnospiraceae.

5. The method according to claim 4 wherein the gram-positive bacteria are selected from the group consisting of Faecalibacterium prausnitzii and Roseburia intestinalis.

Assignees

• Inst Nat Sante Rech Med
• Assist Publique—Hopitaux De Paris
• Inst Nat De La Rech Agronomique Inra
• Univ Paris Sud

Inventors

• Dore Joël
• Faivre Jamila
• Moniaux Nicolas
• Brechot Christian
• Darnaud Marion

Classifications

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• A23C9/1322

  Inorganic compounds; Minerals, including organic salts thereof, oligo-elements; Amino-acids, peptides, protein-hydrolysates or derivatives; Nucleic acids or derivatives; Yeast extract or autolysate; Vitamins; Antibiotics; Bacteriocins · CPC title

• A23L33/18

  Peptides; Protein hydrolysates · CPC title

• A61K38/1709 Primary

  from mammals · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title