Shen Ling Bai Zhu San promotes gut IgAplasma cells to alleviate chronic diarrhea in mice via increasing systematic glutamine.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Shen Ling Bai Zhu San (SLBZS) is a classical Chinese herbal formula and has been used for treating chronic diarrhea (CD) for several centuries. However, there is a lack of robust evidence on how SLBZS regulates immune function to improve CD. AIM OF THE STUDY: To reveal the spleen-invigorating and antidiarrheal effects of SLBZS in chronic diarrhea mice induced by spleen-deficiency, as well as to explore the underlying mechanism. MATERIALS AND METHODS: Based on the modern living habits, the CD model was induced by multiple factors, and the antidiarrheal effects of SLBZS were evaluated by monitoring body weight, diarrhea scored, fecal water content, etc. Additionally, the flow cytometry and metabolomics were used to explore the changes of colonic B cells and related metabolites. Subsequently, the inhibitor of glutamine synthetase and antibiotic-treated mice were used separately to evaluate the roles of glutamine and gut microbiota in the treatment of CD with SLBZS. RESULTS: High-dose SLBZS significantly alleviates CD and repairs the gut mucosal barrier. Moreover, SLBZS significantly increased the percentages of germinal center B cells, plasma cells (PC), IgAPC, IgAbacteria and the content of sIgA. Metabolomics results indicated that glutamine metabolism may be vital pathway for SLBZS treatment of CD, which has also been confirmed by supplementation of glutamine in CD mice and the used of inhibitor of glutamine synthetase. Lastly, we demonstrated that SLBZS promotes the differentiation of B cells to produce sIgA in a microbiota-dependent manner. CONCLUSIONS: Our study proved that elevated glutamine plays a crucial role in the treatment of CD with SLBZS by promoting the differentiation of B cells to produce sIgA.