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


ABSTRACT: 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.

SUBMITTER: Jain U 

PROVIDER: S-EPMC6555552 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Jain Umang U   Lai Chin-Wen CW   Xiong Shanshan S   Goodwin Victoria M VM   Lu Qiuhe Q   Muegge Brian D BD   Christophi George P GP   VanDussen Kelli L KL   Cummings Bethany P BP   Young Erick E   Hambor John J   Stappenbeck Thaddeus S TS  

Cell host & microbe 20180816 3


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  ...[more]

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