Lactobacillus murinus alleviate intestinal ischemia/reperfusion injury through promoting the release of interleukin-10 from M2 macrophages via Toll-like receptor 2 signaling

Abstract

Background Intestinal ischemia/reperfusion (I/R) injury has high morbidity and mortality rates. Gut microbiota is a potential key factor affecting intestinal I/R injury. Populations exhibit different sensitivities to intestinal I/R injury; however, whether this interpopulation difference is related to variation in gut microbiota is unclear. Here, to elucidate the interaction between the gut microbiome and intestinal I/R injury, we performed 16S DNA sequencing on the preoperative feces of C57BL/6 mice and fecal microbiota transplantation (FMT) experiments in germ-free mice. The transwell co-culture system of small intestinal organoids extracted from control mice and macrophages extracted from control mice or Toll-like receptor 2 (TLR2)-deficient mice or interleukin-10 (IL-10)-deficient mice were established separately to explore the potential mechanism of reducing intestinal I/R injury. Results Intestinal I/R-sensitive (Sen) and intestinal I/R-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 differed between Sen and Res mice. The relative abundance of Lactobacillus murinus (L. murinus) at the species level was drastically higher in Res than that in Sen mice. 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 intestinal I/R-induced intestinal injury and improved mouse survival, which depended on macrophages involvement. Further, in vitro experiments indicated that promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. Conclusion The gut microbiome is involved in the postoperative outcome of intestinal I/R. Lactobacillus murinus alleviates mice intestinal I/R injury through macrophages, and promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. This study revealed a novel mechanism of intestinal I/R injury and a new therapeutic strategy for clinical practice.

Association of Gut Microbiota With Intestinal Ischemia/Reperfusion Injury

“…Hu et al found that differences in the pre-II/R gut microbiota, especially in the abundance of Lactobacillus murinus , strongly influence II/R susceptibility and outcome. Moreover, the abundance of Lactobacillus murinus in preoperative feces of cardiopulmonary bypass patients was significantly negatively correlated with postoperative intestinal injury ( Hu et al., 2022 ). Pretreatment of animals with Bifidobacteria prevented II/R-induced bacterial translocation, reduced proinflammatory cytokine release, endotoxin levels, intestinal epithelial apoptosis, disruption of tight junctions, and increased SCFA concentrations, leading to recovery microbiota and mucosal integrity ( Wang et al., 2013b ).…”

“…Hu et al showed that Lactobacillus murinus attenuates II/R injury in mice via macrophages. In addition to intestinal bacterial strains, it has recently been found that intestinal flora metabolites are also non-negligible substances in II/R ( Hu et al., 2022 ). Deng et al al.…”

How do intestinal probiotics restore the intestinal barrier?

“… Kaushal and Kansal (2014) demonstrated that L. acidophilus and B. bifidum increased the phagocytic potential of aged mouse macrophages to improve immunity. A recent probiotic study showed that L. rhamnosus can reduce intestinal ischemia–reperfusion injury in mice by activating IL-10 release from macrophages through the TLR2 receptor signaling pathway ( Hu et al, 2022 ).…”

The role of intestinal microbiota and its metabolites in intestinal and extraintestinal organ injury induced by intestinal ischemia reperfusion injury

“…Lactobacillus murinus relieves intestinal I/R injury by activating TLR2 signal and promotes the release of Interleukin-10 (IL-10) from M2 macrophages, which can significantly prevent intestinal I/R injury. In addition, correlation analysis showed that clinically, the abundance of Lactobacillus murinus in the feces of patients undergoing cardiopulmonary bypass surgery is closely related to the degree of postoperative intestinal I/R injury [67]. The combined use of L. plantarum DSM 9843 and rose hip reduces cecal I/R injury, the oxidative stress level of cecal tissue and the abundance of enterobacter [68].…”

“…Intestinal ischemia/reperfusion (I/R) injury is common in the perioperative period, especially in both surgical and trauma patients, and has high morbidity and mortality associated with it [1][2][3]. Intestinal I/R plays an important role in the pathophysiological evolution of severe infection, trauma, shock, intestinal obstruction, mesenteric artery embolism, abdominal aortic aneurysm surgery, cardiopulmonary bypass surgery, liver transplantation, and small intestine transplantation [4,5].…”