Mechanistically, TMAO exacerbates IBD pathogenesis by modulating key signaling pathways—including endoplasmic reticulum stress (ERS) via protein kinase RNA-like endoplasmic reticulum kinase (PERK) activation, NF-κB-driven proinflammatory cytokine production, and NLRP3 inflammasome-mediated pyroptosis—thereby disrupting intestinal epithelial integrity, amplifying macrophage and T cell activation, and skewing immune homeostasis toward a proinflammatory milieu. Here, EIF2AK3 is linked to inflammatory bowel disease.