Lithium carbonate alleviates colon inflammation through modulating gut microbiota and metabolism in a GPR43-dependent manner. Lithium carbonate alleviates colon inflammation

Background: Recent evidence suggests that neuropsychiatric stabilizers take a place in resolving gastrointestinal disorders. Lithium carbonate (LC) is one of the most commonly used drugs for bipolar disorder clinically. Here, we investigate the protective effect of LC on colon inflammation and clarify its underlying mechanism of gut microbiota and metabolism modulation.Methods: Colitis was induced by daily consecutive administration of 2.5% dextran sulfate sodium (DSS) solution for 7 days. Analysis of gut microbiota was carried out by 16S rRNA gene sequencing. Antibiotic cocktail treatment (ABX) and fecal microbiota transplantation (FMT) were conducted to evaluate the role of gut microbiota. The frequency of immune cells in colonic lamina propria (LP) were phenotyped by flow cytometry. Results: LC treatment significantly alleviated colon inflammation in a gut microbiota-dependent manner, as evidenced by increased gut microbial diversity and altered flora compositions. Notably, LC treatment upregulated short chain fatty acids (SCFAs)-producing bacteria, especially Akkermansia muciniphila (A. muciniphila), and transformed metabolites SCFAs profiles. LC activated anti-inflammatory Treg cell responses in colonic LP in a G-protein coupled receptor 43 (GPR43)-dependent mechanism. ABX, FMT and single bacteria gavage experiments were conducted to confirm above mechanism.Conclusions: Our results demonstrate the role of LC as a potential modulator of gut microbiota and metabolites in the prevention and treatment of colon inflammation. Therefore, therapeutic manipulation of the gut microbiome–metabolome-immune axis, as observed A. muciniphila-SCFAs-Treg cell axis in our study, might provide a new strategy for the management of IBD.