The antitumour effects of caloric restriction are mediated by the gut microbiome

The authors show that caloric restriction increases the intestinal abundance of Bifidobacterium bifidum, which in turn blunts tumour development in mice. Calorie restriction (CR) and intermittent fasting (IF) without malnutrition reduce the risk of cancer development. Separately, CR and IF can also lead to gut microbiota remodelling. However, whether the gut microbiota has a role in the antitumour effect related to CR or IF is still unknown. Here we show that CR, but not IF, protects against subcutaneous MC38 tumour formation through a mechanism that is dependent on the gut microbiota in female mice. After CR, we identify enrichment of Bifidobacterium through 16S rRNA sequencing of the gut microbiome. Moreover, Bifidobacterium bifidum administration is sufficient to rescue the antitumour effect of CR in microbiota-depleted mice. Mechanistically, B. bifidum mediates the CR-induced antitumour effect through acetate production and this effect is also dependent on the accumulation of interferon-gamma(+)CD8(+) T cells in the tumour microenvironment. Our results demonstrate that CR can modulate the gut taxonomic composition, which should be of oncological significance in tumour growth kinetics and cancer immunosurveillance.

Automated summary

The study reveals that caloric restriction increases the presence of Bifidobacterium bifidum in the intestine, which ultimately inhibits tumor development in mice. Caloric restriction and intermittent fasting, without causing malnutrition, have been found to reduce the risk of cancer. Additionally, both caloric restriction and intermittent fasting can alter the composition of the gut microbiota. It is shown in this study that caloric restriction, but not intermittent fasting, protects against subcutaneous MC38 tumor formation in female mice through a mechanism involving the gut microbiota. These findings highlight the oncological significance of modulating the gut taxonomic composition in tumor growth and cancer immunosurveillance.