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

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

Ngôn ngữ: eng

Ký hiệu phân loại: 972.8202 *Central America

Thông tin xuất bản: England : Nature communications , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 231751

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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