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  • Review Article
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Roles of the gut microbiota in immune-related adverse events: mechanisms and therapeutic intervention

Nature Reviews Clinical Oncology volume 22, pages 499–516 (2025)Cite this article

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Abstract

Immune checkpoint inhibitors (ICIs) constitute a major breakthrough in the field of cancer therapy; their use has resulted in improved outcomes across various tumour types. However, ICIs can cause a diverse range of immune-related adverse events (irAEs) that present a considerable challenge to the efficacy and safety of these treatments. The gut microbiota has been demonstrated to have a crucial role in modulating the tumour immune microenvironment and thus influences the effectiveness of ICIs. Accumulating evidence indicates that alterations in the composition and function of the gut microbiota are also associated with an increased risk of irAEs, particularly ICI-induced colitis. Indeed, these changes in the gut microbiota can contribute to the pathogenesis of irAEs. In this Review, we first summarize the current clinical challenges posed by irAEs. We then focus on reported correlations between alterations in the gut microbiota and irAEs, especially ICI-induced colitis, and postulate mechanisms by which these microbial changes influence the occurrence of irAEs. Finally, we highlight the potential value of gut microbial changes as biomarkers for predicting irAEs and discuss gut microbial interventions that might serve as new strategies for the management of irAEs, including faecal microbiota transplantation, probiotic, prebiotic and/or postbiotic supplements, and dietary modulations.

Key points

  • Although immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, they often induce immune-related adverse events (irAEs) that are not only a common cause of treatment discontinuation, which might compromise oncological outcomes, but can also reduce patient quality of life and even have fatal outcomes.

  • Clinical cohort studies and preclinical data indicate that gut microbiota composition has a substantial influence on the risk and severity of irAEs.

  • The mechanisms underlying the association of the gut microbiota with irAEs include antigen cross-reactivity, modulation of intestinal barrier integrity, interplay with the immune environment, regulation of microbial homeostasis and others.

  • Distinct gut microbial alterations could potentially be used to predict the occurrence of irAEs.

  • Gut microbial modulation strategies such as faecal microbiota transplantation, dietary modifications, and supplementation with probiotics, prebiotics and/or postbiotics, have promise for the treatment and perhaps even prevention of irAEs.

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Fig. 1: Mechanisms underlying links between the gut microbiota and irAEs.

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Acknowledgements

The work of the authors is supported by grants from the National Key R&D Program of China (2020YFA0509200 to J.-Y.F.), the National Natural Science Foundation of China (82250005 and 82330086 to J.-Y.F.) and the Shanghai Municipal Hospital Gastroenterology clinical competence improvement and advancement specialist alliance (SHDC22024302 to J.-Y.F.).

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  1. Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Ya-Qi Gao, Yong-Jie Tan & Jing-Yuan Fang

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Y.-.Q.G. researched data for the article, Y.-.Q.G. and Y.-J.T. wrote the article, and J.-Y.F. contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.

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Gao, YQ., Tan, YJ. & Fang, JY. Roles of the gut microbiota in immune-related adverse events: mechanisms and therapeutic intervention. Nat Rev Clin Oncol 22, 499–516 (2025). https://doi.org/10.1038/s41571-025-01026-w

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