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Cell Host Microbe. 2017 Jul 12;22(1):25-37.e6. doi: 10.1016/j.chom.2017.06.007.

Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation.

Author information

1
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
2
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
3
Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
4
Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
5
Novartis Institutes for BioMedical Research, Novartis Campus, 4056 Basel, Switzerland.
6
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
7
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
8
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: xavier@molbio.mgh.harvard.edu.

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.

KEYWORDS:

Muc2; Peptostreptococcus; indoleacrylic acid; indolepropionic acid; mucus; organoid

PMID:
28704649
PMCID:
PMC5672633
DOI:
10.1016/j.chom.2017.06.007
[Indexed for MEDLINE]
Free PMC Article

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