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

Author

Listed:
  • Mina Tsenkova

    (University of Luxembourg)

  • Madita Brauer

    (University of Luxembourg
    University of Luxembourg)

  • Vitaly Igorevich Pozdeev

    (University of Luxembourg)

  • Marat Kasakin

    (University of Luxembourg)

  • Susheel Bhanu Busi

    (University of Luxembourg
    UK Centre for Ecology and Hydrology)

  • Maryse Schmoetten

    (University of Luxembourg)

  • Dean Cheung

    (University of Luxembourg)

  • Marianne Meyers

    (University of Luxembourg)

  • Fabien Rodriguez

    (University of Luxembourg)

  • Anthoula Gaigneaux

    (University of Luxembourg)

  • Eric Koncina

    (University of Luxembourg)

  • Cedric Gilson

    (University of Luxembourg)

  • Lisa Schlicker

    (University of Luxembourg)

  • Diran Herebian

    (Heinrich Heine University)

  • Martine Schmitz

    (University of Luxembourg)

  • Laura Nies

    (University of Luxembourg)

  • Ertan Mayatepek

    (Heinrich Heine University)

  • Serge Haan

    (University of Luxembourg)

  • Carine Beaufort

    (University of Luxembourg
    Centre Hospitalier de Luxembourg)

  • Thorsten Cramer

    (RWTH University Hospital Aachen)

  • Johannes Meiser

    (Luxembourg Institute of Health)

  • Carole L. Linster

    (University of Luxembourg)

  • Paul Wilmes

    (University of Luxembourg
    University of Luxembourg)

  • Elisabeth Letellier

    (University of Luxembourg)

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.

Suggested Citation

  • Mina Tsenkova & Madita Brauer & Vitaly Igorevich Pozdeev & Marat Kasakin & Susheel Bhanu Busi & Maryse Schmoetten & Dean Cheung & Marianne Meyers & Fabien Rodriguez & Anthoula Gaigneaux & Eric Koncina, 2025. "Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56678-0
    DOI: 10.1038/s41467-025-56678-0
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    References listed on IDEAS

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    1. Shuo Han & Will Treuren & Curt R. Fischer & Bryan D. Merrill & Brian C. DeFelice & Juan M. Sanchez & Steven K. Higginbottom & Leah Guthrie & Lalla A. Fall & Dylan Dodd & Michael A. Fischbach & Justin , 2021. "A metabolomics pipeline for the mechanistic interrogation of the gut microbiome," Nature, Nature, vol. 595(7867), pages 415-420, July.
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