Carmona-Alcocer, V. | bioRxiv Science

bioRxiv2026

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

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.

physiology↗

bioRxiv2025

Chrono-atlas of cell-type specific daily gene expression rhythms in the regenerating colon

The circadian clock is a molecular timer present throughout the body, including the gastrointestinal tract, where it regulates daily rhythms in physiology through the timing of rhythmic gene expression. Dysfunctional rhythms, caused by loss of clock timing and/or environmental disruption is implicated with gastrointestinal dysfunction and pathology. The large intestine (colon) is composed of many different types of cells with distinct gene expression programs and functions. How daily rhythms in transcript abundance are coordinated in the intestine at a cell-specific level is not known. Using single cell transcriptomics, we analyzed 24-hour gene expression in all major cell types of the proximal and distal regions of the colon following injury. We find that daily gene expression is not uniform: rhythmic genes, including circadian clock components, clock targets, and systemic programs, differ in their timing and are cell-type specific. Cells of the epithelium, stroma, and immune system to display strong rhythms in metabolic, protein processing, and stress response genes during regeneration. While stromal and muscle cells exhibit robust circadian clock gene rhythms irrespective of injury, epithelial cells show weaker clock oscillations that become 12-hours antiphasic during regeneration. These data, completed with smFISH validation, reveal an unexpected complexity to daily transcript levels in the colon, and provide a resource for future studies by identifying the cellular source of 24-hour transcript rhythms.

physiology↗