Abstract

Inflammatory Bowel Disease (IBD) is a chronic inflammatory intestinal disorder with complex etiology, closely associated with gut microbiota dysbiosis. This study demonstrates that Eubacterium rectale ( ER ), a beneficial commensal bacterium, alleviates dextran sulfate sodium (DSS)-induced colitis in mice, as evidenced by improved clinical symptoms, restored intestinal barrier integrity, and reduced pro-inflammatory cytokine levels. Mechanistic investigations revealed that ER specifically upregulates the expression of glutaminase 2 (GLS2), ameliorates DSS-induced disturbances in glutamine (Gln) metabolism within intestinal epithelial cells, and subsequently inhibits the NF-κB signaling pathway to exert anti-inflammatory effects. Further validation showed that GLS2 deficiency abolishes the anti-inflammatory effects of ER . Collectively, this work identifies a therapeutically relevant mechanism: ER mitigates colitis via the GLS2/NF-κB axis. These insights pave the way for developing ER -derived live biotherapeutic products for IBD.