AbdelGhani O, Elhariri S, Bhatnagar P, Aung HH, Abdel Wahab M, Eid N. Appendix in ulcerative colitis pathogenesis and therapy: An updated narrative review. World J Gastrointest Pathophysiol 2026; 17(2): 122072 [DOI: 10.4291/wjgp.v17.i2.122072]
Corresponding Author of This Article
Nabil Eid, MD, PhD, Associate Professor, Department of Human Biology, School of Medicine, IMU University, Bukit Jalil, Kuala Lumpur 57000, Malaysia. nabilsaleheid@imu.edu.my
Research Domain of This Article
Gastroenterology & Hepatology
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review-article
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AbdelGhani O, Elhariri S, Bhatnagar P, Aung HH, Abdel Wahab M, Eid N. Appendix in ulcerative colitis pathogenesis and therapy: An updated narrative review. World J Gastrointest Pathophysiol 2026; 17(2): 122072 [DOI: 10.4291/wjgp.v17.i2.122072]
Omar AbdelGhani, Department of Surgery, Ministry of Health and Population, Cairo, 11737, Egypt
Sherreen Elhariri, Department of Surgery, School of Medicine, IMU University, Seremban 70300, Negeri Sembilan, Malaysia
Payal Bhatnagar, Department of Pharmaceutical Technology, School of Pharmacy, IMU University, Kuala Lumpur 57000, Malaysia
Htar Htar Aung, Nabil Eid, Department of Human Biology, School of Medicine, IMU University, Kuala Lumpur 57000, Malaysia
Mohamed Abdel Wahab, Department of Pediatrics, School of Medicine, IMU University, Clinical Campus, Batu Paha 83000, Johor, Malaysia
Author contributions: AbdelGhani O and Eid N wrote the final draft of the manuscript; Bhatnagar P prepared the figures; Elhariri S wrote and revised the manuscript; Aung HH and Abdel Wahab M revised the manuscript; all authors have read and approved the final manuscript.
AI contribution statement: AI tools (specifically ChatGPT) and GRAMMARLY were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors. For file “answering-reviewers”, we used AI just for grammar and language check, not for generation of paragraphs.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Nabil Eid, MD, PhD, Associate Professor, Department of Human Biology, School of Medicine, IMU University, Bukit Jalil, Kuala Lumpur 57000, Malaysia. nabilsaleheid@imu.edu.my
Received: April 9, 2026 Revised: April 30, 2026 Accepted: May 13, 2026 Published online: June 22, 2026 Processing time: 69 Days and 4.3 Hours
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.
Core Tip: Recent clinical studies indicate the potential of the appendix as an immunological and microbial niche in ulcerative colitis pathogenesis. Induction of immune dysregulation and acceleration of inflammation are associated with autophagy dysfunction in colonic cells, and possibly the appendix. Current evidence suggests the potential of appendectomy as an adjunctive therapeutic strategy, improving remission in selected patients.
