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A murine commensal protozoan relieves Clostridium difficile infection through regulating the arginine metabolism and the host intestinal immune response

Yang, H.; Wu, X.; Zang, W.; Zhou, Y.; Li, X.; Wang, L.; Cui, W.; Kou, Y.; Wang, Y.; Gu, B.

2023-05-07 microbiology
10.1101/2023.05.06.539719 bioRxiv
Show abstract

Antibiotic-induced dysbiosis is a key predisposing factor for Clostridium difficile infection (CDI), fecal microbiota transplantation (FMT) is recommended for treating CDI. However, the mechanisms remain unclear. Here, we uncover that one integral member of the murine gut microbiota, a commensal protozoan from mice, Tritrichomonas musculis (T. mu), that reduced intestinal damage by inhibiting the recruitment of neutrophil and secretion of IL-1{beta}, and increased Th1 cell differentiation and secretion of IFN-{gamma}, which increased the goblet cell and secretion of mucin to protect the intestinal mucosa. The T. mu upregulated the key enzymes of arginine metabolism iNOS, ASS, OTC and down-regulated ARG1 in CDI mice, resulting in an increase in arginine, citrulline and a decrease in ornithine, which worked together to regulate the host intestinal immune response and alleviate CDI. This work reveals the interaction mechanism between intestinal commensal eukaryotes and pathogenic bacteria, and also provide new ideas for treating CDI.

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