Alterations in gut microbiota and their association with colonic permeability and inflammation in LPS-induced sepsis mice

Sepsis is a leading cause of death in critically ill patients. This work aimed to to investigate alterations in the gut microbiota and their mechanisms of action in a sepsis-modeling mouse using 16S rRNA sequencing. Twenty normal mice and seventy septic mice were exposed to lipopolysaccharides (LPS) in the study. The diversity, structure, and composition of the gut microbiota were examined using 16S rRNA sequencing on days 1, 3, 5, and 7. Immunohistochemistry was used to measure the expressions of the tight junction protein zonula occludens-1 (ZO-1) and occluding to assess intestinal barrier damage. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of serum interleukin-17 (IL-17) and interleukin-23 (IL-23) to assess the degree of inflammation. Over time, mice exposed to LPS exhibited marked dysbiosis of the intestinal microbiota, characterized by changes in microbiota composition. This was primarily due to the colonization of pathogenic bacteria belonging to the phylum Proteobacteria and a significant decrease in the relative abundance of beneficial bacteria belonging to the phyla Firmicutes and Bacteroidetes. Additionally, the structure of the intestinal microbiota in LPS mice was altered, resulting in asignificant reduction in diversity. Bacteroides were identified as a biomarker through genus-level LEfSe analysis. The expressions of colonic occludin and ZO-1 were significantly down-regulated, while the level of IL-17 was elevated in LPS mice. This study suggests that the gut microbiota undergoes changes during a week of sepsis in mice, and that microbiota dysfunction may be closely related to intestinal barrier dysfunction and changes in the IL-17/IL-23 axis.