Background: Alcohol consumption is an established risk factor for colon cancer (CRC). Identifying cofactor(s) that modulate the effect of alcohol on colon inflammation and carcinogenesis could help risk stratification for CRC. Disruption of circadian rhythm by light/dark shift, promotes alcohol induced colonic inflammation and cancer. More recently, we found that abnormal food timing causes circadian rhythm disruption and promotes alcohol associated colon carcinogenesis. In this study, we examined the interaction of wrong time feeding (WTF) and alcohol on CRC-related pathways, in relation to changes in microbial community.
Method: Polyposis mice (TS4Cre x cAPCΔ468) underwent 4 conditions: Alcohol or Water and feeding during the light (wrong-time fed/WTF) or during the dark (right-time fed/RTF). Colonic gene expression was analysed by RNA-seq. Microbiota analysis was done on the cecal content using 16s rRNA. Modelling was used to estimate the extent of the gene expression changes that could be related to the changes in the microbial composition.
Results: The circadian rhythm pathway was the most altered pathway by the WTF treatment, indicating that WTF is disruptive to the colonic circadian rhythm. Pathway analysis revealed interaction of WTF with alcohol in dysregulating pathways related to colon carcinogenesis. Similarly, the interaction of alcohol and WTF was detected at multiple parameters of the colonic microbiota including α- and β-diversity, as well as the community structure. Our modelling revealed that almost third of total gene alterations induced by our treatments could be related to alteration in the abundance of the microbial taxa.
Conclusion: These data support the promoting effect of abnormal food timing alcohol-associated CRC related pathways in the colon, and suggest colon dysbiosis as a targetable mechanisms.