Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Cell Rep Med. 2023 Mar 21;4(3):100979. doi: 10.1016/j.xcrm.2023.100979.
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) 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.
人群对肠道缺血/再灌注（I/R）的易感性存在显著差异，但潜在机制仍不清楚。在这里，我们表明，小鼠对 I/R 诱导的肠源败血症的易感性存在显著差异。值得注意的是，耐肠源败血症的小鼠中的米那普仑（MC）含量明显更高。我们还揭示，包括肠道 I/R 损伤患者在内的体外循环患者的术前粪便 MC 含量与术后胃肠道损伤的易感性相关。我们表明，MC 可减轻野生型小鼠的 I/R 损伤，但不能减轻肠道上皮芳香烃受体（AHR）基因条件性敲除小鼠（AHR）或 IL-22 基因缺失小鼠（IL-22）的 I/R 损伤。总之，我们的结果表明，肠道微生物群影响对 I/R 诱导的肠源败血症的易感性，并且肠道微生物群衍生的 MC 以 AHR/ILC3/IL-22 信号依赖性方式在对肠道 I/R 的耐受中发挥关键作用，揭示了肠道 I/R 的病理机制、潜在的预防和治疗药物以及治疗策略。
