Yang J, Wei H, Zhou Y, et al. - In mice, a high-fat diet (HFD) promotes colorectal tumorigenesis by inducing gut microbial dysbiosis, metabolomic dysregulation with elevated lysophosphatidic acid (LPA), and gut barrier dysfunction.

• When compared with CD-fed mice, HFD promoted colorectal tumorigenesis in both azoxymethane (AOM)-treated mice and Apc ^min/+ mice.

• Antibiotic depletion of the gut microbiota reduced colon tumor formation in HFD-fed mice.

• In HFD-fed mice, there was a significant shift in gut microbiota composition, with increased pathogenic bacteria Alistipes sp. Marseille-P5997 and Alistipes sp. 5CPEGH6, and decreased probiotic Parabacteroides distasonis, as well as impaired gut barrier function.

• Furthermore, HFD-modulated gut microbiota promotes colorectal tumorigenesis in AOM-treated germ-free mice, implying that gut microbiota is required for HFD-associated colorectal tumorigenesis.

• HFD-fed mice also had altered gut metabolites, including elevated LPA, which has been shown to promote colorectal cancer cell proliferation and impair cell junction.

• Furthermore, uninhibited transfer of stools from HFD-fed mice to germ-free mice increased colonic cell proliferation, impaired gut barrier function, and induced oncogenic gene expression.