The anti-tumor effects of caloric restriction are mediated by the gut microbiome

Calorie restriction（CR) as well as intermittent fasting (IF) without malnutrition have been shown to reduce the risk of cancer development. Separately, CR and IF can also lead to gut microbiota remodeling. However, whether the gut microbiota plays a role in the anti-tumor effect related to CR or IF is still unknown. Here we show that CR, but not IF, protects against subcutaneous MC38 tumor formation through a mechanism that is dependent on the gut microbiota in female mice. Following CR, we identify enrichment of Bifidobacterium through 16S rRNA sequencing of the gut microbiome. Moreover, B. bifidum administration is sufficient to rescue the anti-tumor effect of CR in microbiota-depleted mice. Mechanistically, B. bifidum mediates the CR-induced anti-tumor effect through acetate production, and is also dependent on the accumulation of IFNγ+CD8+T cells in the tumor microenvironment. Our results demonstrate that CR can modulate the gut taxonomic composition, which is of oncological significance in tumor growth kinetics and cancer immunosurveillance.