Jinzhi protects lipopolysaccharide-treated mice against mortality by repairing intestinal mucosal barrier damage and intestinal microecology

Abstract

Objective: Intestinal mucosal barrier damage is an important mechanism for the development of sepsis and multiple organ dysfunction syndrome. At present, there are no satisfactory and effective methods for the protection of the intestinal mucosal barrier. Jinzhi, the first fecal microbiota transplantation worldwide, is often used to treat critically ill patients; however, the specific mechanism involved in this process remains unclear. The aim of this study was to investigate the therapeutic effect and mechanism of Jinzhi intervention on mice with sepsis induced through treatment with lipopolysaccharide (LPS).

Methods: Mice were intraperitoneally injected with LPS to simulate intestinal mucosal barrier function damage in sepsis; intervention was performed through the oral administration of Jinzhi. The effect of Jinzhi on LPS-induced sepsis was analyzed by comparing the vital signs and survival rate of mice under different treatments. Pathological staining and enzyme-linked immunosorbent assay were used to identify the effects of LPS or treatment with Jinzhi on the intestinal mucosal barrier in mice. The effect of LPS or treatment with Jinzhi on the intestinal flora was analyzed via 16S rRNA gene sequencing of ileal contents.

Results: Immunohistochemistry and enzyme-linked immunosorbent assay showed that treatment with LPS increased levels of inflammatory factors (interleukin-1α, interleukin-6, tumor necrosis factor-α), caspase-3, and caspase-8 in the serum and ileum, and destroyed the tight junction between epithelial cells. Intervention with Jinzhi reduced levels of serum LPS and tumor necrosis factor-α, and repaired the tight junction between epithelial cells. Furthermore, 16S rRNA gene sequencing analysis showed that treatment with Jinzhi improved the diversity and physiological function of the intestinal flora.

Conclusions: These results suggest that Jinzhi may be a promising option for the treatment of sepsis caused by LPS, and emphasize that Jinzhi exerts a recovery effect on the imbalance of intestinal flora.

Keywords: 16S rRNA sequencing; Intestinal mucosal barrier damage; Jinzhi; Lipopolysaccharide; Sepsis.