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Gut microbiota-derived short-chain fatty acids and their role in human health and disease

Nature Reviews Microbiology volume 23, pages 635–651 (2025)Cite this article

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Abstract

Short-chain fatty acids (SCFAs) are a group of organic compounds produced by the fermentation of dietary fibre by the human gut microbiota. They play diverse roles in different physiological processes of the host with implications for human health and disease. This Review provides an overview of the complex microbial metabolism underlying SCFA formation, considering microbial interactions and modulating factors of the gut environment. We explore the multifaceted mechanistic interactions between SCFAs and the host, with a particular focus on the local actions of SCFAs in the gut and their complex interactions with the immune system. We also discuss how these actions influence intestinal and extraintestinal diseases and emerging therapeutic strategies using SCFAs.

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Fig. 2: Molecular interactions of SCFAs with the host.
Fig. 3: Immune regulation by SCFAs.
Fig. 4: SCFA modulation strategies.

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Acknowledgements

P.L. received funding from the Scottish Government Rural and Environment Service and Analytical Services Division.

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    Indrani Mukhopadhya

  2. Rowett Institute, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK

    Petra Louis

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Mukhopadhya, I., Louis, P. Gut microbiota-derived short-chain fatty acids and their role in human health and disease. Nat Rev Microbiol 23, 635–651 (2025). https://doi.org/10.1038/s41579-025-01183-w

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