Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation.

Abstract

Host factors in the intestine help select for bacteria that promote health. Certain commensals can utilize mucins as an energy source, thus promoting their colonization. However, health conditions such as inflammatory bowel disease (IBD) are associated with a reduced mucus layer, potentially leading to dysbiosis associated with this disease. We characterize the capability of commensal species to cleave and transport mucin-associated monosaccharides and identify several Clostridiales members that utilize intestinal mucins. One such mucin utilizer, Peptostreptococcus russellii, reduces susceptibility to epithelial injury in mice. Several Peptostreptococcus species contain a gene cluster enabling production of the tryptophan metabolite indoleacrylic acid (IA), which promotes intestinal epithelial barrier function and mitigates inflammatory responses. Furthermore, metagenomic analysis of human stool samples reveals that the genetic capability of microbes to utilize mucins and metabolize tryptophan is diminished in IBD patients. Our data suggest that stimulating IA production could promote anti-inflammatory responses and have therapeutic benefits.

• Authors: Marta Wlodarska, Chengwei Luo, Raivo Kolde, Eva d'Hennezel, John W Annand, Cortney E Heim, Philipp Krastel, Esther K Schmitt, Abdifatah S Omar, Elizabeth A Creasey, Ashley L Garner, Sina Mohammadi, Daniel J O'Connell, Sahar Abubucker, Timothy D Arthur, Eric A Franzosa, Curtis Huttenhower, Leon O Murphy, Henry J Haiser, Hera Vlamakis, Jeffrey A Porter, Ramnik J Xavier
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 22 Issue 1 Pg. 25-37.e6 (Jul 12 2017) ISSN: 1934-6069 [Electronic] United States
• PMID: 28704649 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Indoles
• Mucin-2
• Mucins
• indoleacrylic acid

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Bacteria (classification, genetics, metabolism)
• Bacteroides (genetics, metabolism)
• Clostridiales (genetics, metabolism)
• Colon (microbiology, pathology)
• Cytokines (metabolism)
• Dysbiosis (metabolism)
• Humans
• Indoles (metabolism, pharmacology)
• Inflammation (metabolism)
• Inflammatory Bowel Diseases
• Intestinal Mucosa (injuries, metabolism, microbiology)
• Intestines (microbiology)
• Mice
• Mucin-2 (genetics, metabolism)
• Mucins (genetics, metabolism)
• Organoids
• Peptostreptococcus (metabolism)
• Symbiosis