Gut barrier dysfunction treatment and prevention

Patent metadata

Field	Value
Publication number	US-9925222-B2
Application number	US-201514729211-A
Country	US
Kind code	B2
Filing date	Jun 3, 2015
Priority date	Dec 7, 2012
Publication date	Mar 27, 2018
Grant date	Mar 27, 2018

Abstract

Methods are disclosed for treating and preventing gut barrier dysfunction or an illness associated with gut barrier dysfunction in a subject comprising administering to the subject bacterium that produce an indole or an indole metabolite and for identifying compounds and bacteria for use in treatment and prevention of gut barrier dysfunction or an illness associated with gut barrier dysfunction.

First claim

What is claimed is:

1. A method of treating or preventing gut barrier dysfunction, an illness associated with gut barrier dysfunction, toxic or inflammatory injury to intestines, or leaky intestinal syndrome in a subject comprising administering to the subject a therapeutic effective amount of a bacterium, wherein the bacterium is Clostridium sporogenes comprising a tryptophanase operon, wherein in the presence of tryptophan, the tryptophanase operon is induced and the bacterium produces indole-3-propionic acid or indoleacetic acid from tryptophan,
wherein pregnane X receptor (PXR) is activated in gut apical enterocvtes, thereby decreasing intestinal permeability and inflammation.

2. The method of claim 1 , wherein the bacterium is administered orally to the subject.

3. The method of claim 1 , wherein the subject has irritable bowel syndrome, inflammatory bowel disease, intestinal allergic syndrome or celiac sprue.

4. The method of claim 1 , wherein the bacterium colonizes the gut of the subject.

5. The method of claim 1 , wherein the subject is a human.

6. The method of claim 1 , wherein indole-3-propionic acid or indoleacetic produced by the bacterium induces target genes of PXR in intestinal mucosa in the subject, wherein the target genes are selected from the group consisting of Multi-drug resistant gene (Mdr1), Cytochrome P450, family 3, subfamily a, polypeptide 11 (Cyp3a11) and Uridine diphosphate glucuronosyltransferase family 1 member a1 (Ugt1a1).

7. The method of claim 1 , wherein indole-3-propionic acid or indoleacetic produced by the bacterium reduces a mucosal myeloperoxidase enzyme activity in the subject.

Assignees

• Albert Einstein College Medicine Yeshiva Univ
• Albert Einstein College Medicine Inc

Inventors

• Mani Sridhar
• Mukherjee Subhajit

Classifications

• Y10T436/145555

  Hetero-N · CPC title

• C07D211/92

  with a hetero atom directly attached to the ring nitrogen atom · CPC title

• C07D211/56 Primary

  Nitrogen atoms (nitro radicals C07D211/38) · CPC title

• G16H50/20

  for computer-aided diagnosis, e.g. based on medical expert systems · CPC title

• C12Q1/025

  for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics (antimicrobial activity C12Q1/18) · CPC title