Time restricted feeding ameliorates colitis through clock-dependent and nutrition-dependent processes

Abstract

Inflammatory Bowel Disease (IBD) is rising worldwide and requires the development of preventative strategies to lower its incidence. Circadian rhythms, daily cycles of physiology, have been shown to be implicated in IBD in both clinical and laboratory studies. We tested if a 12-hour Time-Restricted Feeding (TRF) dietary regimen, that improves circadian rhythms, could ameliorate colitis using a mouse model of disease. We find that TRF indeed protects mice from the damaging effects of colitis, and boosts the rhythmic expression of transcripts related to the clock, cell proliferation, and barrier function. Under TRF, mice exhibit lower disease symptoms, changes in microbiota, and reduced inflammatory tissue damage. These outcomes are not clock-dependent: colitis in Bmal1 mutants without circadian rhythms is also rescued by TRF. However, in this context alterations to the transcriptome are distinct from that found in clock-wildtype controls. Together our data support the translation of a 12-hour TRF in IBD, and highlight clock-dependent and nutrition-dependent changes accompanying colitis rescue.