Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism
Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism
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肠道微生物群的改变通过宿主代谢介导的途径诱发抑郁样行为
DOI：
10.1038/mp.2016.44
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发表时间：
2016-06-01
影响因子：
11
通讯作者：
Xie, P.
中科院分区：
文献类型：
--
作者：
Zheng, P.;Zeng, B.;Xie, P.
重性抑郁障碍（MDD）是复杂的基因-环境相互作用的结果。根据世界卫生组织的数据，MDD是全球残疾的主要原因，也是全球总体疾病负担的主要贡献者。然而，明确的环境机制的病理生理学的MDD仍然难以捉摸。肠道微生物组是一个越来越被认可的环境因素，可以通过微生物-肠道-大脑轴塑造大脑。我们在这里表明，与常规饲养的健康对照小鼠相比，无菌（GF）小鼠中肠道微生物群的缺乏导致强迫游泳试验中的不动时间减少。此外，从临床采样来看，MDD患者和健康对照的肠道微生物组成存在显着差异，其中MDD患者的特征是厚壁菌门、放射菌门和拟杆菌门的相对丰度发生显着变化。与来自健康对照个体的“健康微生物群”的定植相比，来自MDD患者的“抑郁微生物群”的GF小鼠的粪便微生物群移植导致抑郁样行为。携带“抑郁微生物群”的小鼠主要表现出参与碳水化合物和氨基酸代谢的微生物基因和宿主代谢物的紊乱。这项研究表明，肠道微生物组的生态失调可能在通过宿主代谢介导的途径中对抑郁样行为的发展起因果作用。
Major depressive disorder (MDD) is the result of complex gene-environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiology of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clinical sampling, the gut microbiotic compositions of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with 'depression microbiota' derived from MDD patients resulted in depression-like behaviors compared with colonization with 'healthy microbiota' derived from healthy control individuals. Mice harboring 'depression microbiota' primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host's metabolism.