The microbiota drives circadian entrainment of tryptophan metabolism in the stressed gut

Tryptophan is a precursor of key molecules involved in stress-related disorders and circadian rhythmicity plays a crucial role in gut-brain axis signaling. The physiological effects of chronic stress often manifest as a disruption in circadian rhythms and as a dysregulation of host-microbiota crosstalk. However, little is known about the effects of acute stress on the gut and subsequent implications for circadian entrainment of physiology at the host-microbe interface. Here we show that a 15-min acute stressor is sufficient to alter microbial tryptophan metabolism and microbiota-dependent gut paracellular permeability in vivo. We demonstrate that tryptophan-metabolizing bacteria and their predicted metabolites exhibit circadian rhythmicity; and that microbiota depletion affects gut tissue rhythmicity of barrier function and expression of genes involved in host tryptophan metabolism. Germ-free status and depletion by antibiotics differentially affected circadian rhythmicity of genes involved in host tryptophan degradation. Time-of-day interacts with microbial depletion to alter the gut response to acute stress in a region-dependent manner. Together, these findings highlight a new role for the gut microbiota in the response to host-directed stressors and in regulating circadian rhythms of tryptophan metabolism and barrier function in the gut, with implications for host-microbe crosstalk in the gut-brain axis.