Gut Microbiota Regulates Stress Responsivity via the Circadian System

Stress and circadian systems are bidirectionally interconnected to maintain appropriate responses to external stimuli. The gut microbiota has been shown to modulate these systems independently, but its role in regulation of the integration of stress and circadian signals remains unknown. Here we show that microbiota disruption results in rhythmic alterations in the brain transcriptome and metabolome in pathways key to stress responsivity. This was coupled with alterations in the rhythmic profile of glucocorticoid secretion, impaired response to acute stress and altered stress-sensitive behaviors. Moreover, we show that diurnal oscillations of gut microbes regulate glucocorticoid secretion and unmask the microbial underpinnings of such changes. Thus, the gut microbiota regulates diurnal oscillations of stress responsiveness and is necessary to respond adaptively to psychological stressors throughout the day.