Colonization with Altered Schaedler Flora Impacts Leukocyte Adhesion in Mesenteric Ischemia-Reperfusion Injury

Abstract

The microbiota impacts mesenteric ischemia-reperfusion injury, aggravating the interaction of leukocytes with endothelial cells in mesenteric venules. The role of defined gut microbiomes in this life-threatening pathology is unknown. To investigate how a defined model microbiome affects the adhesion of leukocytes in mesenteric ischemia-reperfusion, we took advantage of gnotobiotic isolator technology and transferred altered Schaedler flora (ASF) from C3H/HeNTac to germ-free C57BL/6J mice. We were able to detect all eight bacterial taxa of ASF in fecal samples of colonized C57BL/6J mice by PCR. Applying qRT-PCR for quantification of species-specific 16S rDNA sequences of ASF bacteria, we found a major shift in the abundance of ASF 500, which was greater in C57BL/6J mice relative to the C3H/HeNTac founder breeding pair. Using high-speed epifluorescence intravital microscopy to visualize the venules of the small bowel mesentery, we found that gnotobiotic ASF-colonized mice showed reduced leukocyte adherence, both pre- and post-ischemia. Relative to germ-free mice, the counts of adhering leukocytes were increased pre-ischemia but did not significantly increase in ASF-colonized mice in the post-ischemic state. Collectively, our results suggest a protective role of the minimal microbial consortium ASF in mesenteric ischemia-reperfusion injury.

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

“…FMT results indicated that the abundance of L. murinus in preoperative feces of patients is related to different sensitivities of mice to intestinal I/R injury. Altered Schaedler flora contains L.murinus-colonized mice reduced leukocyte deposition in mesenteric I/R injury as compared to conventionally raised specific pathogenfree controls mice [9]. More importantly, treatment with L. murinus significantly prevented intestinal I/R-induced intestinal injury and improved mouse survival, which may depend on macrophage involvement.…”

“…In addition, L. murinus mediates anti-inflammatory effects in calorie-restricted mice [8]. Altered Schaedler flora contains L.murinus-colonized mice reduced leukocyte deposition in mesenteric I/R injury as compared to conventionally raised specific pathogen-free controls mice [9]. However, the role and mechanism of L. murinus in intestinal I/R injury remains unclear.…”

Bibliometric and visual analysis of intestinal ischemia reperfusion from 2004 to 2022

“…Preoperative fasting by mimicking clinical requirements for patients was performed before the mouse model of intestinal I/R, and its alteration of flora metabolites was found beneficial for resisting intestinal I/R injury ( 84 ). Specific flora such as Bifidobacterium bifidum PRL2010 can attenuate intestinal I/R injury ( 85 ), and altered schaedler flora affected leukocyte adhesion in intestinal I/R injury ( 86 ). In terms of specific mechanisms, the flora metabolite pravastatin drives IL-13 release from type II innate lymphocytes via IL-33/ST2 signaling and attenuates intestinal I/R injury ( 87 ).…”

A compendium of predicted growths and derived symbiotic relationships between 803 gut microbes in 13 different diets

“…The Altered Schaedler Flora (ASF) ( Bayer et al., 2021 ) can be considered to be a small model community allowing further investigations into multi-species metabolic cooperation. When simulated under contrasting dietary conditions, the emergent community behavior of ASF was seen to depend on the nature of the available nutrients (Supplementary Figure 3).…”