title: Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism.
abstract: 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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: P
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: B
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: L
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: S
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: X
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: H
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: N D
authors.initials: ND
authors.lastname: Melgiri
authors.affiliation: Mind & Brain Theme, South Australian Health and Medical Research Institute and Department of Psychiatry, School of Medicine, Flinders University, Adelaide, SA, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Licinio
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: H
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: P
authors.initials: P
authors.lastname: Xie
mesh_terms: D000818:Animals; D003863:Depression / Q000378:metabolism* / Q000382:microbiology; D003865:Major Depressive Disorder / Q000378:metabolism / Q000382:microbiology; D064806:Dysbiosis / Q000378:metabolism / Q000523:psychology; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D059647:Gene-Environment Interaction; D006801:Humans; D051379:Mice; D064307:Microbiota / Q000502:physiology