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The appendix and ulcerative colitis — an unsolved connection

Nature Reviews Gastroenterology & Hepatology volume 20, pages 615–624 (2023)Cite this article

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Abstract

The appendix is thought to have a role in the pathogenesis of ulcerative colitis, but the nature and basis of this association remains unclear. In this Perspective, we consider the biology of the appendix with respect to its immunological function and the microbiome, and how this relates to evidence that supports the involvement of the appendix in ulcerative colitis. In experimental models, removal of the inflamed appendix prevents colitis, and in human observational studies, appendectomy is associated with protection against ulcerative colitis. Further, among people who develop ulcerative colitis, appendectomy before diagnosis might influence the course and outcomes of the disease — some evidence suggests that it protects against colectomy but could increase the risk of colorectal cancer. Appendectomy after onset of ulcerative colitis seems to have disparate consequences. Clinical trials to understand whether appendectomy has a role in the treatment of ulcerative colitis are ongoing. Major questions about the role of the appendix in the pathogenesis of ulcerative colitis remain unanswered, and further research is needed to establish whether the connection is clinically relevant.

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Fig. 1: The immunological composition and function of the appendix in health and ulcerative colitis.
Fig. 2: Proposed relationships between appendicitis, appendectomy and the risk of ulcerative colitis and its outcomes.

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Acknowledgements

The authors thank J. Gregory, Certified Medical Illustrator, Icahn School of Medicine at Mount Sinai, for the original versions of the figures.

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Authors and Affiliations

  1. The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Manasi Agrawal, Saurabh Mehandru & Jean-Frederic Colombel

  2. Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark

    Manasi Agrawal, Kristine H. Allin & Tine Jess

  3. Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark

    Kristine H. Allin & Tine Jess

  4. Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Saurabh Mehandru & Jeremiah Faith

  5. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jeremiah Faith

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Correspondence to Manasi Agrawal.

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Competing interests

M.A. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK129762-02). S.M. has received research grants from Genentech and Takeda; payment for lectures from Genentech, Morphic and Taleda; and consulting fees from Arena Pharmaceuticals, Ferring, Morphic and Takeda. J.F. has received consulting fees from Vedanta Biosciences. J.-F.C. has received research grants from AbbVie, Janssen Pharmaceuticals and Takeda; payment for lectures from AbbVie, Amgen, Allergan, Ferring Pharmaceuticals, Shire and Takeda; has received consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Glaxo Smith Kline, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microbia, Novartis, PBM Capital, Pfizer, Protagonist Therapeutics, Sanofi, Takeda, TiGenix and Vifor; and holds stock options in Intestinal Biotech Development. The other authors declare no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks C. Buskens, C. Fiocchi, E. Mizoguchi and K. Okazaki for their contribution to the peer review of this work.

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Agrawal, M., Allin, K.H., Mehandru, S. et al. The appendix and ulcerative colitis — an unsolved connection. Nat Rev Gastroenterol Hepatol 20, 615–624 (2023). https://doi.org/10.1038/s41575-023-00774-3

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