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Influence of biological sex in inflammatory bowel diseases

Nature Reviews Gastroenterology & Hepatology volume 22, pages 415–437 (2025)Cite this article

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Abstract

The incidence of inflammatory bowel disease (IBD) has risen in the past decades and has emerged as a global health issue. IBD is characterized by chronic inflammation of the gastrointestinal tract. There is compelling evidence for the role of biological sex in IBD epidemiology, pathophysiology, disease progression, symptoms and extra-intestinal diseases. IBD disease course, management and therapies differ between men and women, yet there is a paucity of analysis of sex as a factor. This Review discusses the known influence of sex-linked genetic factors, hormones and hormone receptors in IBD incidence, prevalence, disease burden and clinical manifestation. Furthermore, we review the mechanisms underlying these sex-dependent effects on the dysregulation of gastrointestinal mucosal immunity (immune, epithelial barrier and microbiota) in IBD. To support the progressive inclusion of sex in the study of IBD, we summarize the current standard research methodology that should be implemented to investigate sex as a biological variable in IBD studies. Enhanced comprehension of the influence of sex in IBD pathophysiology will advance the development of targeted therapies and improve patient care.

Key points

  • Biological sex differentially affects inflammatory bowel disease (IBD) subtypes, ulcerative colitis, and Crohn’s disease epidemiology, disease course and symptoms across ages.

  • This article summarizes current knowledge of the effect of biological sex on IBD, highlights research gaps and recommends best practices in research methodology to integrate sex in IBD research.

  • To improve patient care, integration and comprehension of biological sex in IBD, personalized therapeutic strategies and the inclusion of a broader population in preclinical and clinical research are needed.

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Fig. 1: Biological sex differences in IBD epidemiology across age groups.
Fig. 2: Sex chromosomes and hormones in IBD onset and progression across age groups.
Fig. 3: Role of dysregulated ERs in the sex discrepancy of IBD severity.

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Acknowledgements

D.M.T. is supported by the Children’s Hospital Research Institute of Manitoba/Research Manitoba PhD Studentship Award and the Mindel & Tom Olenick Research Studentships in Medicine. C.N.B. is supported in part by the Bingham Chair in Gastroenterology. J.-E.G. is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC). H.K.A. is supported by the University of Manitoba and Canada Research Chair. S.M. is supported by the Canadian Institutes of Health Research and NSERC.

Author information

Author notes

  1. Jean-Eric Ghia

    Present address: University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada

  2. These authors jointly supervised this work: Jean-Eric Ghia, Heather K. Armstrong.

Authors and Affiliations

  1. Rady Faculty of Health Sciences, Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada

    Diane M. Tshikudi, Jean-Eric Ghia & Heather K. Armstrong

  2. Section of Gastroenterology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

    Charles N. Bernstein & Heather K. Armstrong

  3. University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada

    Charles N. Bernstein & Heather K. Armstrong

  4. Section of Endocrinology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

    Suresh Mishra & Heather K. Armstrong

  5. Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada

    Jean-Eric Ghia & Heather K. Armstrong

  6. Rady Faculty of Health Sciences, Department of Internal Medicine, Manitoba Center for Proteomics and System Biology, University of Manitoba, Winnipeg, Manitoba, Canada

    Heather K. Armstrong

  7. Manitoba MS Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada

    Heather K. Armstrong

  8. Rady Faculty of Health Sciences, Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada

    Heather K. Armstrong

  9. Faculty of Agriculture, Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

    Heather K. Armstrong

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Contributions

D.M.T. and H.K.A. researched data for the article. C.N.B., D.M.T., J.-E.G. and H.K.A. contributed substantially to discussion of the content. D.M.T., C.N.B., S.M. and H.K.A. wrote the article. All authors reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Heather K. Armstrong.

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Competing interests

C.N.B. has consulted for Abbvie Canada, Amgen Canada, Bristol Myers Squibb Canada, Eli Lilly, Janssen Canada, Pfizer Canada, Ferring Canada, Pendopharm Canada, Sandoz Canada and Takeda Canada. He has received unrestricted educational grants from Abbvie Canada, Boston Scientific, Fresenius-Kabi Canada, Bristol Myers Squibb Canada, Janssen Canada, Pfizer Canada, Organon Canada and Takeda Canada and research grants from Abbvie, Janssen, Bristol Myers Squibb, Pfizer, Sandoz and Takeda. He has been on speaker’s bureaus of Abbvie Canada, Eli Lilly, Fresenius-Kabi, Takeda Canada, Pfizer Canada and Janssen Canada. J.-E.G. has served as a member of the scientific medical advisory committee for Crohn’s and Colitis Canada and as a member and chair of the research advisory committee for Research Manitoba. The other authors declare no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks Gionata Fiorino, Alessandro Armuzzi, Giuseppe Privitera and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Tshikudi, D.M., Bernstein, C.N., Mishra, S. et al. Influence of biological sex in inflammatory bowel diseases. Nat Rev Gastroenterol Hepatol 22, 415–437 (2025). https://doi.org/10.1038/s41575-025-01038-y

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