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Mechanistically, TMAO exacerbates IBD pathogenesis by modulating key signaling pathwaysincluding endoplasmic reticulum stress (ERS) via protein kinase RNA-like endoplasmic reticulum kinase (PERK) activation, NF-B-driven proinflammatory cytokine production, and NLRP3 inflammasome-mediated pyroptosisthereby disrupting intestinal epithelial integrity, amplifying macrophage and T cell activation, and skewing immune homeostasis toward a proinflammatory milieu

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