Western‐style high fat, low fiber diet causes progression of colorectal peritoneal metastases in mice

BACKGROUND: Multimodality (physical, dietary, psychological) prehabilitation is associated with a disease-free survival advantage after colorectal cancer surgery; however, the underlying mechanism is unknown. We measured the effects of a western-style diet on gut dysbiosis, antitumor immunity, and cancer progression in a surgical mouse model of metastatic colorectal cancer and attempted to mitigate its effects with isolated dietary prehabilitation. METHODS: Before surgery and tumor induction, mice were given either a western-style diet for 6 weeks, chow for 6 weeks, or 4 weeks of a western-style diet followed by 2 weeks of chow. Expelled stool was collected for analysis of the fecal microbiome. Four weeks after surgery, tumors were quantified and collected for analysis with an immunofluorescence panel. RESULTS: The western-style diet was obesogenic. Fecal microbiome analysis illustrated that the western diet induced a severe and lasting dysbiosis as measured by alpha diversity metrics, pathogenic overgrowth and Firmicutes to Bacteroidetes ratio, which was partially rescued by prehabilitation. Mice fed the western diet demonstrated increased tumor bulk and decreased intratumoral immune cell infiltrate compared with chow-fed mice. prehabilitation rescued the intratumoral immune effects, but not tumor bulk. CONCLUSION: An obesogenic, no fiber western-style diet increased gut dysbiosis and tumor bulk while decreasing antitumor immunity in our mouse model, which was partially rescued by prehabilitation. Microbiome-targeted prehabilitation for colorectal cancer surgery is a promising paradigm and further translational research is warranted.