Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate

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.

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Publication Details

Journal
Nature Communications
Published
2025-02-20
DOI
https://doi.org/10.1038/s41467-025-56678-0
Citations
28
Primary Topic
Diet and metabolism studies
Type
article
Field-Weighted Citation Impact
32.60

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article

Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate

Maryse Schmoetten, Cedric Gilson, Vitaly I. Pozdeev, Carine E. de Beaufort et al.
28 citations
Nature Communications
Diet and metabolism studies
32.60
article

Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate

Maryse Schmoetten, Cedric Gilson, Vitaly I. Pozdeev, Carine E. de Beaufort, Thorsten Cramer, Mina Tsenkova, Anthoula Gaigneaux, Laura de Nies, Marianne Meyers, Diran Agaid Herebian, Carole L. Linster, Marat F. Kasakin, Lisa Schlicker, Elisabeth Letellier, Ertan Mayatepek, Martine Schmitz, Serge Haan, Paul Wilmes, Susheel Bhanu Busi, Fabien Rodriguez, Eric Koncina, Madita Brauer, Johannes Meiser, Dean Cheung
article en
28 citations

Abstract

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.

Nature CommunicationsVol. 16(1)
Centre Hospitalier de Luxembourg (LU), University of Luxembourg (LU), Düsseldorf University Hospital (DE), UK Centre for Ecology & Hydrology (GB), Luxembourg Institute of Health (LU), Universitätsklinikum Aachen (DE), Arbed (Luxembourg) (LU), Heinrich Heine University Düsseldorf (DE), RWTH Aachen University (DE)
Université du Luxembourg, Fondation Cancer, European Commission, Fonds National de la Recherche Luxembourg, International Council for Canadian Studies, Fonds De La Recherche Scientifique - FNRS, Action LIONS Vaincre le Cancer, National Institutes of Health, Common Fund
Good health and well-being
Openalex Percentile: Top 0%
Diet and metabolism studies
32.60
DOIOpen Access PDFOpenAlex
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