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A role for microglia in mediating the microbiota–gut–brain axis

Nature Reviews Immunology (2025)Cite this article

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Abstract

Microglia, the resident immune cells of the brain, are now recognized as being active participants in the onset and progression of many neurological and neuropsychiatric disorders. As a result, substantial effort has been made in finding ways to target, deplete or modulate the aberrant phenotypes of the microglia that are present in these different disease states, albeit with varied levels of success. The gut microbiota has recently emerged as a master regulator of microglia throughout the lifespan; here, we propose that this microbiota–microglia cross-talk may have major implications for our understanding of neurological disorders and neuropsychiatric diseases. We focus on the latest advances in understanding gut–microglia communication in the context of microglial heterogeneity and microglia-related functions, as well as considering the evidence for effects of these pathways on diseases and disorders of the central nervous system. We also address the challenges, opportunities and clinical implications of this emerging area of research.

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Fig. 1: Pathways for gut microbiota–microglia communication.
Fig. 2: Effects of microbiota-targeting interventions on microglia across different diseases.

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Acknowledgements

The authors thank their funding sources. L.K. acknowledges support from the ChadTough Defeat DIPG Foundation, and J.F.C. acknowledges the support of Science Foundation Ireland (SFI/12/RC/2273_P2). The authors also thank C. Cuesta for her help in generating the original version of Fig. 2.

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  1. APC Microbiome Ireland, University College Cork, Cork, Ireland

    Lily Keane, Gerard Clarke & John F. Cryan

  2. Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland

    Lily Keane & John F. Cryan

  3. Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland

    Gerard Clarke

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Keane, L., Clarke, G. & Cryan, J.F. A role for microglia in mediating the microbiota–gut–brain axis. Nat Rev Immunol (2025). https://doi.org/10.1038/s41577-025-01188-9

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