Stress and circadian systems are interconnected through the hypothalamic-pituitary-adrenal (HPA) axis to maintain responses to external stimuli. Yet, the mechanisms of how such signals are orchestrated remain unknown. Here, we uncover the gut microbiota as a regulator of HPA-axis rhythmicity. Microbial depletion disturbs the brain transcriptome and metabolome in stress-responding pathways in the hippocampus and amygdala across the day. This is coupled with a dysregulation of the circadian pacemaker in the brain that results in perturbed glucocorticoid rhythmicity. The resulting hyper-activation of the HPA axis at the sleep/wake transition drives time-of-day-specific impairments of the stress response and stress-sensitive behaviors. Finally, microbiota transplantation confirmed that diurnal oscillations of gut microbes underlie altered glucocorticoid secretion and that L. reuteri is a candidate strain for such effects. Our data offer compelling evidence that the microbiota regulates stress responsiveness in a circadian manner and is necessary to respond adaptively to stressors throughout the day.

中文翻译：

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肠道微生物群通过昼夜节律系统调节压力反应性


压力和昼夜节律系统通过下丘脑-垂体-肾上腺 （HPA） 轴相互连接，以维持对外部刺激的反应。然而，这些信号如何编排的机制仍然未知。在这里，我们揭示了肠道微生物群作为 HPA 轴节律的调节因子。微生物耗竭会干扰海马体和杏仁核中应激反应途径中的大脑转录组和代谢组。再加上大脑中昼夜节律起搏器失调，导致糖皮质激素节律紊乱。在睡眠/觉醒过渡时 HPA 轴的过度激活导致压力反应和压力敏感行为的一天中特定时间的损害。最后，微生物群移植证实肠道微生物的昼夜振荡是糖皮质激素分泌改变的基础，并且罗伊氏乳 杆菌是这种作用的候选菌株。我们的数据提供了令人信服的证据，表明微生物群以昼夜节律的方式调节压力反应性，并且是全天对压力源做出适应性反应所必需的。