CNRS, IFCE, INRAE, Université de Tours, PRC, 37380 Nouzilly, France.
INRAE, ISP, Université de Tours, UMR 1282, 37380 Nouzilly, France.
Psychoneuroendocrinology. 2022 Feb;136:105594. doi: 10.1016/j.psyneuen.2021.105594. Epub 2021 Nov 20.
Chronic stress and the gut microbiota appear to comprise a feed-forward loop, which contributes to the development of depressive disorders. Evidence suggests that memory can also be impaired by either chronic stress or microbiota imbalance. However, it remains to be established whether these could be a part of an integrated loop model and be responsible for memory impairments. To shed light on this, we used a two-pronged approach in Japanese quail: first stress-induced alterations in gut microbiota were characterized, then we tested whether this altered microbiota could affect brain and memory function when transferred to a germ-free host. The cecal microbiota of chronically stressed quails was found to be significantly different from that of unstressed individuals with lower α and β diversities and increased Bacteroidetes abundance largely represented by the Alistipes genus, a well-known stress target in rodents and humans. The transfer of this altered microbiota into germ-free quails decreased their spatial and cue-based memory abilities as previously demonstrated in the stressed donors. The recipients also displayed increased anxiety-like behavior, reduced basal plasma corticosterone levels and differential gene expression in the brain. Furthermore, cecal microbiota transfer from a chronically stressed individual was sufficient to mimic the adverse impact of chronic stress on memory in recipient hosts and this action may be related to the Alistipes genus. Our results provide evidence of a feed-forward loop system linking the microbiota-gut-brain axis to stress and memory function and suggest that maintaining a healthy microbiota could help alleviate memory impairments linked to chronic stress.
慢性应激和肠道微生物群似乎构成了一个正反馈循环,这有助于抑郁障碍的发展。有证据表明,慢性应激或微生物群失衡也会导致记忆受损。然而,这些是否可以成为一个集成的循环模型的一部分,并导致记忆损伤,仍有待确定。为了阐明这一点,我们在日本鹌鹑中采用了双管齐下的方法:首先,我们研究了慢性应激对肠道微生物群的改变,然后,我们测试了这种改变的微生物群在转移到无菌宿主时是否会影响大脑和记忆功能。与未受应激的个体相比,慢性应激鹌鹑的盲肠微生物群具有显著差异,其 α 和 β 多样性较低,拟杆菌门的丰度增加,主要由 Alistipes 属代表,该属是啮齿动物和人类中众所周知的应激靶点。将这种改变的微生物群转移到无菌鹌鹑中,降低了它们的空间和基于线索的记忆能力,正如之前在应激供体中所证明的那样。受者还表现出焦虑样行为增加、基础血浆皮质酮水平降低和大脑中差异基因表达。此外,从慢性应激个体转移盲肠微生物群足以模拟应激对宿主记忆的不良影响,这种作用可能与 Alistipes 属有关。我们的研究结果为连接微生物群-肠道-大脑轴与应激和记忆功能的正反馈循环系统提供了证据,并表明维持健康的微生物群可能有助于减轻与慢性应激相关的记忆损伤。