Colitis_Biological_Clock

The inflammatory bowel disease (IBD) etiology remains unclear, treatment options unsatisfactory and disease development difficult to predict for individual patients. Dysbiosis of the gastrointestinal microbiota and disruption of the biological clock have been implicated in IBD and studied as diagnostic and therapeutic targets. Here we examine the relationship of IBD to the biological clock and gut microbiota by using the IL-10 deficient (IL-10-/-) mouse model for microbiota-dependent spontaneous colitis in combination with altered (4h/4h) light/dark cycles to disrupt and time-restricted feeding (TRF) to restore circadian rhythmicity. We show that while altered light/dark cycles disrupted the intestinal clock in wild type mice, IL-10-/- mice were characterized by altered microbiota composition, impaired intestinal clock and microbiota rhythmicity irrespective of external clock disruption, which had no consistent colitis-promoting effect on IL-10-/- mice. TRF, however, delayed the onset of experimental colitis, reduced the expression of inflammatory markers and increased the expression of clock genes in the intestine, and increased gut microbiota rhythmicity in IL-10-/- mice. Compositional changes and reduced rhythmicity of the fecal microbiota preceded colitis development and could be modeled to predict the onset of colitis symptoms for individual IL-10-/- mice across different experiments. Our findings provide perspectives for new diagnostic and TRF-based, therapeutic applications in IBD that should be further explored.