Biology subjects

Khan, W. I.

Publications and source records attributed to Khan, W. I..

2 recordsLinked to original sources

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↗

bioRxiv2026

Epithelial function of the circadian clock gene, Bmal1, in regulating the mucosa.

Circadian rhythms, 24-hour repeating oscillations in daily physiology, are implicated in maintaining intestinal homeostasis. These rhythms are driven by the circadian clock, a molecular timekeeper found throughout cells of the body, including those of the intestinal epithelium. Loss of clock function has been found to worsen colitis; however, it is not clear how the clock impacts regeneration which enables a tissue to return to its homeostatic set point following an injury. To investigate these questions, we used a conditional knockout of the core clock gene, Bmal1, in mouse colon epithelial cells. Our data show that prior to injury Bmal1 promotes colon mucus production, which increases in thickness and within goblet cells when mice are active and begin feeding. Bmal1 loss lowers mucus production but does not drive an apparent tissue phenotype until the system is injured and regenerates itself. In this context, Bmal1 epithelial loss drives a male-specific colitis phenotype and a delay in the ability of colon epithelial cells of both male and female mice to resolve injury to return to their homeostatic set point. Our data suggest that epithelial sex-specific clock rhythms are needed for optimal colon barrier homeostasis.

physiology↗