Appendix in ulcerative colitis pathogenesis and therapy: An updated narrative review.

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon. Its pathogenesis has been linked to chronic intestinal inflammation stemming from genetic predisposition, immune dysregulation, changes in gut microbiome, and various environmental factors. There is emerging evidence for autophagy dysfunction in the UC setting, suggesting a compromise of the intestinal epithelial barrier and microbial clearance in patients, resulting in chronic activation of the immune system. There is growing evidence that the appendix functions as a critical priming site for UC. Dysregulation of various lymphocyte subsets, dysbiosis, propagation of inflammation into the colon, as well as autophagy dysfunction, have been listed as contributing to this early appendiceal priming phase. While initially thought of as a vestigial organ, current evidence points towards the appendix as an active immunological and microbial hub. Epidemiological data demonstrate an inverse association between early appendectomy and UC risk, suggesting its potential as a therapeutic strategy. According to recent ACCURE (2025) and COSTA (2026) clinical trials, improved remission outcomes were observed post-appendectomy in selected patients, particularly in patients unresponsive to biologic therapy. Together, the evidence positions appendectomy as a legitimate adjunctive treatment option for UC, warranting further mechanistic and clinical investigation. In this narrative review, current evidence on the pathogenesis and risk factors of UC are summarized, including the emerging role of the appendix and the therapeutic potential of appendectomy in UC.