Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate
Tsenkova, Mina 
ORCID: https://orcid.org/0000-0001-9814-7921; Brauer, Madita; Pozdeev, Vitaly Igorevich; Kasakin, Marat; Busi, Susheel Bhanu ORCID: https://orcid.org/0000-0001-7559-3400; Schmoetten, Maryse; Cheung, Dean; Meyers, Marianne; Rodriguez, Fabien; Gaigneaux, Anthoula ORCID: https://orcid.org/0000-0003-0465-3773; Koncina, Eric ORCID: https://orcid.org/0000-0003-4764-1510; Gilson, Cedric ORCID: https://orcid.org/0000-0001-7257-1097; Schlicker, Lisa; Herebian, Diran; Schmitz, Martine; de Nies, Laura; Mayatepek, Ertan ORCID: https://orcid.org/0000-0001-8460-3738; Haan, Serge ORCID: https://orcid.org/0000-0002-1248-7018; de Beaufort, Carine; Cramer, Thorsten ORCID: https://orcid.org/0000-0002-6462-239X; Meiser, Johannes ORCID: https://orcid.org/0000-0002-9093-6210; Linster, Carole L. ORCID: https://orcid.org/0000-0001-7143-0719; Wilmes, Paul ORCID: https://orcid.org/0000-0002-6478-2924; Letellier, Elisabeth ORCID: https://orcid.org/0000-0001-8242-9393.
2025
Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate.
Nature Communications, 16, 1792.
16, pp.
10.1038/s41467-025-56678-0
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Abstract/Summary
Colorectal cancer (CRC) patients have been shown to possess an altered gut microbiome. Diet is a well-established modulator of the microbiome, and thus, dietary interventions might have a beneficial effect on CRC. An attenuating effect of the ketogenic diet (KD) on CRC cell growth has been previously observed, however the role of the gut microbiome in driving this effect remains unknown. Here, we describe a reduced colonic tumor burden upon KD consumption in a CRC mouse model with a humanized microbiome. Importantly, we demonstrate a causal relationship through microbiome transplantation into germ-free mice, whereby alterations in the gut microbiota were maintained in the absence of continued selective pressure from the KD. Specifically, we identify a shift toward bacterial species that produce stearic acid in ketogenic conditions, whereas consumers were depleted, resulting in elevated levels of free stearate in the gut lumen. This microbial product demonstrates tumor-suppressing properties by inducing apoptosis in cancer cells and decreasing colonic Th17 immune cell populations. Taken together, the beneficial effects of the KD are mediated through alterations in the gut microbiome, including, among others, increased stearic acid production, which in turn significantly reduces intestinal tumor growth.
| Item Type: | Publication - Article |
|---|---|
| Digital Object Identifier (DOI): | 10.1038/s41467-025-56678-0 |
| UKCEH and CEH Sections/Science Areas: | Environmental Pressures and Responses (2025-) |
| ISSN: | 2041-1723 |
| Additional Information. Not used in RCUK Gateway to Research.: | Open Access paper - full text available via Official URL link. |
| Additional Keywords: | cancer microenvironment, microbiology |
| NORA Subject Terms: | Health Biology and Microbiology |
| Related URLs: | |
| Date made live: | 21 Feb 2025 15:51 +0 (UTC) |
| URI: | https://nora.nerc.ac.uk/id/eprint/538946 |
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