Bifidobacterium pseudolongum‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 Pathway

Carvacrol and thymol (CAT) have been widely recognized for their antimicrobial and anti-inflammatory properties, yet their specific effects on colitis and the mechanisms involved remain insufficiently understood. This study establishes a causative link between CAT administration and colitis mitigation, primarily through the enhancement of Bifidobacterium pseudolongum abundance in the colon. This increase promotes the production of secondary bile acids, particularly hyodeoxycholic acid (HDCA) and 12-ketodeoxycholic acid (12-KCAC), which exert anti-inflammatory effects. Notably, CAT does not alleviate colitis symptoms in germ-free mice, indicating the necessity of gut microbiota. This research uncovers a novel regulatory mechanism where HDCA and 12-KCAC inhibit colonic inflammation by reducing the expression of transmembrane guanylate cyclase 1A in the colonic epithelium. This downregulation elevates intracellular Ca