Prodigiosin derived from chromium-resistant Serratia sp. prevents inflammation and modulates gut microbiota homeostasis in DSS-induced colitis mice.

ABSTRACT

Prodigiosin (PG) is a secondary metabolite of microorganisms with anticancer, antimalarial, antibacterial and immunomodulatory effects. However, the modulatory effects on gut microbiome and intestinal immune microenvironment have never been explored in the ulcerative colitis (UC) mice model. In this study, 2.5% dextran sulfate sodium (DSS) induced UC mice model was constructed to investigate the effects of PG derived from a chromium-resistant Serratia sp. on the intestinal flora and inflammatory response. The results showed that prodigiosin administration attenuated the DSS-induced UC symptoms, including preventing the reduction of colonic length and DSS-induced mortality. Furthermore, prodigiosin ameliorated the DSS-induced gut microbiota community dysbiosis by restoring the abundance of Bacteroidota. At the genus level, the declined abundance of Bifidobacterium, Allobaculum and Akkermannia in UC mice was elevated by the treatment of PG. Pathological results by H&E staining showed that PG prevented the appearance of distortion and atrophy of crypt and neutrophil infiltration in a dose-dependent manner. RT-PCR revealed that the expression levels of the inflammatory factors IL-1ß, IL-6 and IL-10 were significantly suppressed, and the expression of the intestinal tight junction protein Claudin-1, Occludin and ZO-1 were upregulted in PG-treated UC mice. Conclusively, our results revealed that prodigiosin effectively prevented inflammatory response and protected intestinal barrier integrity of DSS-induced colitis mice via modulating gut microbiota community structure, suppressing inflammatory factors' expression, and accelerating the expression of intestinal tight junction protein. These results will provide new insights into the interaction of prodigiosin with intestinal microbiota homeostasis and its application in clinical against inflammatory bowel disease.