The gut microbiota predicts and time-restricted feeding delays experimental colitis

Abstract

The etiology of inflammatory bowel disease (IBD) 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 and studied as diagnostic and therapeutic targets. Here, we examine the relationship of IBD to biological clock and gut microbiota by using the IL-10 deficient (IL-10-/-) mouse model for microbiota-dependent spontaneous colitis in combination with altered (4 h/4 h) 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 (WT) 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 delayed colitis onset 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 and could predict 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.