Increased intestinal permeability and lipopolysaccharide contribute to swainsonine-induced systemic inflammation.

ABSTRACT

Long-term consumption of swainsonine could be poisonous to livestock, including facilitating apoptosis by impairing lysosomal function and inhibiting autophagic degradation, leading to liver inflammation and even death in livestock. However, the mechanism by swainsonine induced systemic inflammatory responses remained unclear, especially the effects of swainsonine on intestinal permeability, lipopolysaccharide (LPS) level and oxidative stress response were unknown. In this study, swainsonine increased intestinal permeability as evidenced by the significant down-regulation of colonic goblet cells, Akkermansia muciniphila and intestinal tight junction protein Occludin, Claudin 1 and ZO-1, and the significant up-regulation of mRNA expression level of the intestinal permeability indicator protein tyrosine phosphatase receptor type H (Ptprh) in the ileum of mice. Simultaneously, the elevated LPS biosynthetic genes in intestinal microbiota and increased intestinal permeability facilitated more bacterial endotoxin LPS to enter the blood. High concentration of free-form LPS induced high levels of proinflammatory cytokines and oxidative stress response, thereby causing the systemic inflammation. These findings provided a new perspective on swainsonine-induced systemic inflammation, suggesting that intestinal permeability and free-form LPS level may be the potential trigger factors.