2025-03-06 トロント大学(U of T)
<関連情報>
- https://www.utoronto.ca/news/low-carb-diets-can-drive-development-colorectal-cancer-researchers-find
- https://www.nature.com/articles/s41564-025-01938-4
大腸がんにおけるコリバクチン産生大腸菌の発がんポテンシャルに食物繊維が対抗する Dietary fibre counters the oncogenic potential of colibactin-producing Escherichia coli in colorectal cancer
Bhupesh Kumar Thakur,Yann Malaise,Saurav Roy Choudhury,Anna Neustaeter,Williams Turpin,Catherine Streutker,Julia Copeland,Erin O. Y. Wong,William W. Navarre,David S. Guttman,Christian Jobin,Kenneth Croitoru & Alberto Martin
Nature Microbiology Published:03 March 2025
DOI:https://doi.org/10.1038/s41564-025-01938-4
Abstract
Diet, microbiome, inflammation and host genetics have been linked to colorectal cancer development; however, it is not clear whether and how these factors interact to promote carcinogenesis. Here we used Il10–/– mice colonized with bacteria previously associated with colorectal cancer: enterotoxigenic Bacteroides fragilis, Helicobacter hepaticus or colibactin-producing (polyketide synthase-positive (pks+)) Escherichia coli and fed either a low-carbohydrate (LC) diet deficient in soluble fibre, a high-fat and high-sugar diet, or a normal chow diet. Colonic polyposis was increased in mice colonized with pks+ E. coli and fed the LC diet. Mechanistically, mucosal inflammation was increased in the LC-diet-fed mice, leading to diminished colonic PPAR-γ signalling and increased luminal nitrate levels. This promoted both pks+ E. coli growth and colibactin-induced DNA damage. PPAR-γ agonists or supplementation with dietary soluble fibre in the form of inulin reverted inflammatory and polyposis phenotypes. The pks+ E. coli also induced more polyps in mismatch-repair-deficient mice by inducing a senescence-associated secretory phenotype. Moreover, oncogenic effects were further potentiated by inflammatory triggers in the mismatch-repair-deficient model. These data reveal that diet and host genetics influence the oncogenic potential of a common bacterium.
