Abstract
Perturbations in the intestinal microbiome are strongly linked to the pathogenesis of inflammatory bowel disease (IBD). Bacteria, fungi and viruses all make up part of a complex multi-kingdom community colonizing the gastrointestinal tract, often referred to as the gut microbiome. They can exert various effects on the host that can contribute to an inflammatory state. Advances in screening, multiomics and experimental approaches have revealed insights into host–microbiota interactions in IBD and have identified numerous mechanisms through which the microbiota and its metabolites can exert a major influence on the gastrointestinal tract. Looking into the future, the microbiome and microbiota-associated processes will be likely to provide unparalleled opportunities for novel diagnostic, therapeutic and diet-inspired solutions for the management of IBD through harnessing rationally designed microbial communities, powerful bacterial and fungal metabolites, individually or in combination, to foster intestinal health. In this Review, we examine the current understanding of the cross-kingdom gut microbiome in IBD, focusing on bacterial and fungal components and metabolites. We examine therapeutic and diagnostic opportunities, the microbial metabolism, immunity, neuroimmunology and microbiome-inspired interventions to link mechanisms of disease and identify novel research and therapeutic opportunities for IBD.
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Change history
24 March 2025
A Correction to this paper has been published: https://doi.org/10.1038/s41579-025-01175-w
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Acknowledgements
The authors are supported by US National Institutes of Health (R01DK113136, R01DK121977, R01AI178683 and R01CA286920 to I.D.I), (R01AI163007 to I.D.I and C.-J.G). I.D.I. is supported by the Leona M. and Harry B. Helmsley Charitable Trust, the Irma T. Hirschl Career Scientist Award, the Research Corporation for Science Advancement Award, the Kenneth Rainin Innovator Award, the Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease (PATH) Award and the Cancer Research Institute Lloyd J. Old STAR Award. C.-J.G. was supported by NIH grants DK135816, AI172027, DK132244 and AT013241, the Kenneth Rainin Foundation, the Halvorsen Family Research Scholar in Metabolic Health, the Friedman Center for Nutrition and Inflammation Pilot Award. We thank W.-Y. Lin, J. Patel and S. Chambers for providing editorial support, feedback and help with the figures. I.D.I is a fellow of the Canadian Institute for Advanced Research (CIFAR), programme Fungal Kingdom: Threats and Opportunities.
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Iliev, I.D., Ananthakrishnan, A.N. & Guo, CJ. Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities. Nat Rev Microbiol 23, 509–524 (2025). https://doi.org/10.1038/s41579-025-01163-0
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DOI: https://doi.org/10.1038/s41579-025-01163-0
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