Recurrent application of dietary restriction reduces tumor load and increases lifespan in an intestinal cancer model

Intestinal cancers are highly responsive to their nutrient environment. However, previous studies integrating nutrition into the network of cancer progression are largely inconsistent. We therefore investigated the effects of dietary restriction, which is the most consistently found beneficial nutritional intervention, on the development of intestinal stem cell tumors in a Drosophila melanogaster model. Submission to dietary restriction led to a decline in tumor mass and a morphological as well as functional rehabilitation of the intestine. Nevertheless, flies submitted to dietary restriction exhibited a drastically reduced lifespan due to substantial loss of body mass. To circumvent these destructive consequences, we applied a nutritional regimen consisting of alternating phases of dietary restriction and a fully nutritious diet. Strikingly, the recurrent diet reduced tumor mass and reinstated gut functionality to the same extend as continuous dietary restriction, while restoring the lifespan of tumor-bearing flies back to the level of healthy controls. Overall design: 16S rRNA and transcriptome sequencing were performed to investigate the effects of dietary restriction on the development of intestinal stem cell tumors in a Drosophila melanogaster model.