Temporal Regulation of the Bacterial Metabolite Deoxycholate during Colonic Repair Is Critical for Crypt Regeneration

Umang Jain, Chin Wen Lai, Shanshan Xiong, Victoria M. Goodwin, Qiuhe Lu, Brian D. Muegge, George P. Christophi, Kelli L. VanDussen, Bethany P. Cummings, Erick Young, John Hambor, Thaddeus S. Stappenbeck

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Colonic wound repair is an orchestrated process, beginning with barrier re-establishment and followed by wound channel formation and crypt regeneration. Elevated levels of prostaglandin E2 (PGE2) promote barrier re-establishment; however, we found that persistently elevated PGE2 hinders subsequent repair phases. The bacterial metabolite deoxycholate (DCA) promotes transition through repair phases via PGE2 regulation. During barrier re-establishment, DCA levels are locally diminished in the wound, allowing enhanced PGE2 production and barrier re-establishment. However, during transition to the wound channel formation phase, DCA levels increase to inhibit PGE2 production and promote crypt regeneration. Altering DCA levels via antibiotic treatment enhances PGE2 levels but impairs wound repair, which is rescued with DCA treatment. DCA acts via its receptor, farnesoid X receptor, to inhibit the enzyme cPLA2 required for PGE2 synthesis. Thus, colonic wound repair requires temporally regulated signals from microbial metabolites to coordinate host-associated signaling cascades. Video Abstract: Jain et al. discover that temporal regulation of a bacterial metabolite, deoxycholate, orchestrates phases of colonic repair. In the first phase, deoxycholate is depleted to allow for barrier re-establishment; it re-emerges in the second phase to promote crypt regeneration. Mechanistically, deoxycholate promotes these transitions by modulating PGE2 levels.

Original languageEnglish
Pages (from-to)353-363.e5
JournalCell Host and Microbe
Issue number3
StatePublished - Sep 12 2018


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