爱尔兰科克大学John F. Cryan小组发现，肠道微生物群通过昼夜节律系统调控压力反应。该项研究成果于2024年11月5日在线发表在《细胞—代谢》杂志上。

研究人员发现，肠道微生物群是下丘脑-垂体-肾上腺（HPA）轴节律性的调节因子。微生物的去除干扰了大脑在压力反应路径中的转录组和代谢组，尤其是在海马和杏仁核中，这一现象在全天过程中均可观察到。

与此同时，大脑中的昼夜节律主控器出现失调，导致糖皮质激素的节律性受到干扰。HPA轴在睡眠/觉醒过渡期间的过度激活，驱动了特定时间点的压力反应和压力敏感行为的损害。最后，微生物群移植实验确认了肠道微生物的昼夜振荡，是改变糖皮质激素分泌的基础，且L. reuteri是产生这种效应的候选菌株。

这些数据提供了有力证据，表明肠道微生物群以昼夜节律的方式调控压力反应性，并且对于全天适应性应对压力源是必需的。

据介绍，压力和昼夜节律系统通过HPA轴相互连接，以维持对外界刺激的反应。然而，如何协调这些信号的机制仍然未知。

附：英文原文

Title: Gut microbiota regulates stress responsivity via the circadian system

Author: Gabriel S.S. Tofani, Sarah-Jane Leigh, Cassandra E. Gheorghe, Thomaz F.S. Bastiaanssen, Lars Wilmes, Paromita Sen, Gerard Clarke, John F. Cryan

Issue&Volume: 2024-11-05

Abstract: 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.

DOI: 10.1016/j.cmet.2024.10.003

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00399-1