Gut microbe-derived milnacipran enhances tolerance to gut ischemia/reperfusion injury.

ABSTRACT: There are significant differences in the susceptibility of populations to intestinal ischemia/reperfusion (I/R), but the underlying mechanisms remain elusive. Here, we show that mice exhibit significant differences in susceptibility to I/R-induced enterogenic sepsis. Notably, the milnacipran (MC) content in the enterogenic-sepsis-tolerant mice is significantly higher. We also reveal that the pre-operative fecal MC content in cardiopulmonary bypass patients, including those with intestinal I/R injury, is associated with susceptibility to post-operative gastrointestinal injury. We reveal that MC attenuates mouse I/R injury in wild-type mice but not in intestinal epithelial aryl hydrocarbon receptor (AHR) gene conditional knockout mice (AHR^flox/flox) or IL-22 gene deletion mice (IL

SUBMITTER: Deng F 

PROVIDER: S-EPMC10040455 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature