Lactobacillus Murinus Alleviates Intestinal Ischemia/Reperfusion Injury Through Promoting the Release of Interleukin-10 From M2 Macrophages via Toll-like Receptor 2 Signaling

Abstract BackgroundIntestinal ischemia/reperfusion (I/R) injury has high morbidity and mortality. Gut microbiota is one of the potential key factors affecting intestinal I/R injury. Different populations exhibit different sensitivities to intestinal I/R injury, but whether this is related to differences in gut microbiota is unclear. Here, to elucidate the interaction between the gut microbiome and intestinal I/R injury, we conducted 16S rRNA gene sequencing and fecal microbiota transplantation experiment in an I/R mouse model. Toll-like receptor 2 (TLR2)-deficient mice, interleukin-10 (IL-10)-deficient mice as well as the transwell co-culture system of small intestine organoids and macrophages were used to explore the potential mechanism of bacteria attenuating intestinal I/R injury.ResultsThe intestinal I/R-sensitive (Sen) and resistant (Res) mice were first defined according to different survival outcomes of mice suffering from intestinal I/R. Fecal microbiota composition and diversity prior to intestinal ischemia were different between in Sen and Res mice. The relative abundance of Lactobacillus murinus (L. murinus) at the species level was higher in Res mice than in Sen mice, and the fold change was the largest. Clinically, the abundance of L. murinus in preoperative feces of patients undergoing cardiopulmonary bypass surgery was closely related to the degree of intestinal I/R injury after surgery. Treatment with L. murinus significantly prevented from intestinal I/R-induced intestinal injury and improved the survival of mice, which depends on the participation of macrophages. Further, in vivo and vitro experiments indicated that L. murinus promoted the release of IL-10 from M2 macrophages via activating TLR2 signaling to alleviate intestinal I/R injury. ConclusionGut microbiome is involved in the postoperative outcome of intestinal I/R. L. murinus promotes the release of IL-10 from M2 macrophages through TLR2 signaling to alleviate intestinal I/R injury, revealing a novel mechanism of intestinal I/R injury and new therapeutic strategy for clinical practice.