Ortega Van A, Mercer Emily M, Giesbrecht Gerald F, Arrieta Marie-Claire
Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
International Microbiome Centre, Cumming School of Medicine, Health Sciences Centre, University of Calgary, Calgary, AB, Canada.
Front Microbiol. 2021 Apr 7;12:634539. doi: 10.3389/fmicb.2021.634539. eCollection 2021.
Stress is broadly defined as the non-specific biological response to changes in homeostatic demands and is mediated by the evolutionarily conserved neuroendocrine networks of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Activation of these networks results in transient release of glucocorticoids (cortisol) and catecholamines (epinephrine) into circulation, as well as activation of sympathetic fibers innervating end organs. These interventions thus regulate numerous physiological processes, including energy metabolism, cardiovascular physiology, and immunity, thereby adapting to cope with the perceived stressors. The developmental trajectory of the stress-axis is influenced by a number of factors, including the gut microbiome, which is the community of microbes that colonizes the gastrointestinal tract immediately following birth. The gut microbiome communicates with the brain through the production of metabolites and microbially derived signals, which are essential to human stress response network development. Ecological perturbations to the gut microbiome during early life may result in the alteration of signals implicated in developmental programming during this critical window, predisposing individuals to numerous diseases later in life. The vulnerability of stress response networks to maladaptive development has been exemplified through animal models determining a causal role for gut microbial ecosystems in HPA axis activity, stress reactivity, and brain development. In this review, we explore the evolutionary significance of the stress-axis system for health maintenance and review recent findings that connect early-life microbiome disturbances to alterations in the development of stress response networks.
压力被广泛定义为对稳态需求变化的非特异性生物学反应，由下丘脑 - 垂体 - 肾上腺（HPA）轴和交感神经系统进化保守的神经内分泌网络介导。这些网络的激活导致糖皮质激素（皮质醇）和儿茶酚胺（肾上腺素）短暂释放到循环中，以及支配终末器官的交感神经纤维的激活。这些干预措施因此调节许多生理过程，包括能量代谢、心血管生理和免疫，从而适应并应对感知到的应激源。应激轴的发育轨迹受到多种因素的影响，包括肠道微生物群，它是出生后立即定殖在胃肠道的微生物群落。肠道微生物群通过产生代谢产物和微生物衍生信号与大脑进行交流，这些对于人类应激反应网络的发育至关重要。生命早期肠道微生物群的生态扰动可能导致在这个关键窗口期与发育编程相关的信号发生改变，使个体在生命后期易患多种疾病。通过动物模型确定肠道微生物生态系统在HPA轴活动、应激反应性和大脑发育中的因果作用，已经例证了应激反应网络对适应不良发育的易感性。在这篇综述中，我们探讨应激轴系统对健康维持的进化意义，并回顾将生命早期微生物群紊乱与应激反应网络发育改变联系起来的最新发现。
