1. Academic Validation
  2. Gut microbe-derived milnacipran enhances tolerance to gut ischemia/reperfusion injury

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

  • Cell Rep Med. 2023 Mar 21;4(3):100979. doi: 10.1016/j.xcrm.2023.100979.
Fan Deng 1 Jing-Juan Hu 1 Ze-Bin Lin 1 Qi-Shun Sun 1 Yue Min 1 Bing-Cheng Zhao 1 Zhi-Bin Huang 1 Wen-Juan Zhang 1 Wen-Kao Huang 1 Wei-Feng Liu 1 Cai Li 1 Ke-Xuan Liu 2
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
  • 2 Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: liukexuan705@163.com.
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 (AHRflox/flox) or IL-22 gene deletion mice (IL-22-/-). Collectively, our results suggest that gut microbiota affects susceptibility to I/R-induced enterogenic sepsis and that gut microbiota-derived MC plays a pivotal role in tolerance to intestinal I/R in an AHR/ILC3/IL-22 signaling-dependent manner, revealing the pathological mechanism, potential prevention and treatment drugs, and treatment strategies for intestinal I/R.

Keywords

IL-22; aryl hydrocarbon receptor; enterogenic sepsis; intestinal flora; milnacipran.

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