Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation

被引：698

作者：

Wlodarska, Marta ^{[1
,2
]}

Luo, Chengwei ^{[1
,3
]}

Kolde, Raivo ^{[3
]}

d'Hennezel, Eva ^{[2
]}

Annand, John W. ^{[2
]}

Heim, Cortney E. ^{[1
,2
]}

Krastel, Philipp ^{[4
]}

Schmitt, Esther K. ^{[4
]}

Omar, Abdifatah S. ^{[1
]}

Creasey, Elizabeth A. ^{[3
]}

Garner, Ashley L. ^{[1
]}

Mohammadi, Sina ^{[2
]}

O'Connell, Daniel J. ^{[1
]}

Abubucker, Sahar ^{[2
]}

Arthur, Timothy D. ^{[1
]}

Franzosa, Eric A. ^{[1
,5
]}

Huttenhower, Curtis ^{[1
,5
]}

Murphy, Leon O. ^{[2
]}

Haiser, Henry J. ^{[2
]}

Vlamakis, Hera ^{[1
]}

Porter, Jeffrey A. ^{[2
]}

Xavier, Ramnik J. ^{[1
,3
,6
,7
,8
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Novartis Inst BioMed Res, Chem Biol & Therapeut, Cambridge, MA 02139 USA

[3] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[4] Novartis Inst BioMed Res, Novartis Campus, CH-4056 Basel, Switzerland

[5] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[6] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA

[7] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA

[8] Harvard Med Sch, Boston, MA 02114 USA

来源：

CELL HOST & MICROBE | 2017年 / 22卷 / 01期

关键词：

ARYL-HYDROCARBON RECEPTOR; GUT MICROBIOME; BOWEL-DISEASE; ULCERATIVE-COLITIS; BACTERIAL SYMBIONT; HEME OXYGENASE-1; CROHNS-DISEASE; MUCIN; CELLS; MUCUS;

D O I：

10.1016/j.chom.2017.06.007

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：25 / +

页数：19

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