Gut microbiota-derived 4-guanidinobutanoic acid improves the colonic mucosal barrier via SLC36A1

This study demonstrates that gut commensal bacteria-derived 4-GBA promotes the function of ISCs and the differentiation of goblet cells through SLC36A1, further upregulates the abundance of A. muciniphila, and thereby improves intestinal inflammation. Significantly, SLC36A1 expression is significantly downregulated in colitis patients, while pharmacological targeting with sarcosine promotes epithelial restitution in DSS-induced colonic injury. Our data identify a previously unreported positive-feedback loop wherein gut microbial metabolites modulate host cellular functions to remodel microbial ecology. Furthermore, we establish a causal relationship between SLC36A1 dysregulation and IBD progression. These findings provide potential drug development strategies targeting the intestinal microecology and host SLC36A1 for the improvement of the colonic mucosal barrier.