Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1 Street, 50-368 Wroclaw, Poland.
Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland.
Prog Neuropsychopharmacol Biol Psychiatry. 2020 Aug 30;102:109951. doi: 10.1016/j.pnpbp.2020.109951. Epub 2020 Apr 23.
Accumulating evidence indicates that patients with severe mental disorders, including major depression, bipolar disorder and schizophrenia present with various alterations of the gut microbiota and increased intestinal permeability. In addition, the hypothalamic-pituitary-adrenal (HPA) axis dysregulation and subclinical inflammation have been reported in this group of patients. Although it has been found that the HPA axis dysregulation appears as a consequence of psychosocial stress, especially traumatic life events, the exact mechanisms of this observation remain unclear. Animal model studies have unraveled several mechanisms linking the gut microbiota with the HPA axis dysfunction. Indeed, the gut microbiota can activate the HPA axis through several mediators that cross the blood-brain barrier and include microbial antigens, cytokines and prostaglandins. There is also evidence that various microbial species can affect ileal corticosterone production that may impact the activity of the HPA axis. However, some metabolites released by various microbes, e.g., short-chain fatty acids, can attenuate the HPA axis response. Moreover, several bacteria release neurotransmitters that can directly interact with vagal afferents. It has been postulated that the HPA axis activation can impact the gut microbiota and intestinal permeability. In this article, we discuss various mechanisms linking the gut microbiota with the HPA axis activity and summarize current evidence for a cross-talk between the gut-brain axis and the HPA axis from studies of patients with mood and psychotic disorders. Finally, we show potential clinical implications that can arise from future studies investigating the HPA axis activity with respect to the gut microbiota in severe mental disorders.
越来越多的证据表明，严重精神障碍患者（包括重度抑郁症、双相情感障碍和精神分裂症）存在肠道微生物群的各种改变和肠道通透性增加。此外，该人群还存在下丘脑-垂体-肾上腺（HPA）轴失调和亚临床炎症。虽然已经发现 HPA 轴失调似乎是心理社会应激的结果，尤其是创伤性生活事件，但这一观察的确切机制仍不清楚。动物模型研究揭示了几种将肠道微生物群与 HPA 轴功能障碍联系起来的机制。事实上，肠道微生物群可以通过几种穿过血脑屏障的介质激活 HPA 轴，这些介质包括微生物抗原、细胞因子和前列腺素。还有证据表明，各种微生物物种可以影响回肠皮质酮的产生，从而影响 HPA 轴的活性。然而，各种微生物释放的一些代谢物，如短链脂肪酸，可以减弱 HPA 轴的反应。此外，一些细菌释放的神经递质可以直接与迷走神经传入纤维相互作用。有人假设 HPA 轴的激活会影响肠道微生物群和肠道通透性。在本文中，我们讨论了将肠道微生物群与 HPA 轴活性联系起来的各种机制，并总结了目前关于情绪和精神病性障碍患者的肠道-脑轴和 HPA 轴之间交叉对话的研究证据。最后，我们展示了未来研究调查严重精神障碍患者 HPA 轴活性与肠道微生物群之间关系时可能产生的潜在临床意义。
