Allobaculum stercoricanis and Its Postbiotics Alleviate Dextran Sulfate Sodium (DSS)-Induced Colitis through the Regulation of theTLR4/NF-κB Signaling Pathway

Abstract

Inflammatory bowel disease (IBD) is a chronic intestinal disorder that has become a global public health concern. Postbiotics offer advantages in biosafety and reproducibility over probiotics. Here, we demonstrated that live Allobaculum stercoricanis (A. stercoricanis) and its two postbiotic preparations─inactivated bacterial cells (POST) and cell-free fermentation supernatant (CFS)─effectively alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Integrated gut microbiome and serum metabolomics analyses indicated that these interventions may act through modulating bile acid metabolism and Toll-like receptor signaling pathways. Further investigations combining postbiotic metabolomics, network pharmacology, molecular docking, and molecular dynamics simulations identified α-muricholic acid (α-MCA) as a candidate functional metabolite, with the farnesoid X receptor (FXR) as a potential target. We hypothesize that α-MCA may contribute to ameliorating intestinal inflammation through engagement of FXR and suppression of the TLR4/NF-κB signaling pathway. These findings provide new insights into postbiotic-based therapeutic strategies for IBD.