The gut microbiome modulates the transformation of microglial subtypes

作者全名："Huang, Yu; Wu, Jing; Zhang, Hanping; Li, Yifan; Wen, Lu; Tan, Xunmin; Cheng, Ke; Liu, Yiyun; Pu, Juncai; Liu, Lanxiang; Wang, Haiyang; Li, Wenxia; Perry, Seth W.; Wong, Ma-Li; Licinio, Julio; Zheng, Peng; Xie, Peng"

作者地址："[Huang, Yu; Wu, Jing; Zhang, Hanping; Li, Yifan; Wen, Lu; Tan, Xunmin; Cheng, Ke; Liu, Yiyun; Pu, Juncai; Liu, Lanxiang; Wang, Haiyang; Li, Wenxia; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing 400016, Peoples R China; [Huang, Yu; Wu, Jing; Zhang, Hanping; Li, Yifan; Wen, Lu; Tan, Xunmin; Cheng, Ke; Liu, Yiyun; Pu, Juncai; Liu, Lanxiang; Wang, Haiyang; Li, Wenxia; Xie, Peng] Jin Feng Lab, Chongqing 401329, Peoples R China; [Huang, Yu; Wu, Jing; Zhang, Hanping; Li, Yifan; Wen, Lu; Tan, Xunmin; Liu, Yiyun; Pu, Juncai; Wang, Haiyang; Zheng, Peng; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China; [Liu, Lanxiang] Chongqing Med Univ, Yongchuan Hosp, Dept Neurol, Chongqing 402160, Peoples R China; [Wang, Haiyang] Chongqing Med Univ, Stomatol Hosp, Key Lab Psychoseomadsy, Chongqing 401147, Peoples R China; [Perry, Seth W.; Wong, Ma-Li; Licinio, Julio] SUNY Upstate Med Univ, Coll Med, Dept Psychiat, Syracuse, NY USA; [Zheng, Peng] Chongqing Med Univ, Inst Brain Sci & Dis, Chongqing 400016, Peoples R China"

通信作者："Xie, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing 400016, Peoples R China.; Xie, P (通讯作者)，Jin Feng Lab, Chongqing 401329, Peoples R China.; Zheng, P; Xie, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China.; Zheng, P (通讯作者)，Chongqing Med Univ, Inst Brain Sci & Dis, Chongqing 400016, Peoples R China."

来源：MOLECULAR PSYCHIATRY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000948670400001

JCR分区：Q1

影响因子：9.6

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："Clinical and animal studies have shown that gut microbiome disturbances can affect neural function and behaviors via the microbiota-gut-brain axis, and may be implicated in the pathogenesis of several brain diseases. However, exactly how the gut microbiome modulates nervous system activity remains obscure. Here, using a single-cell nucleus sequencing approach, we sought to characterize the cell type-specific transcriptomic changes in the prefrontal cortex and hippocampus derived from germ-free (GF), specific pathogen free, and colonized-GF mice. We found that the absence of gut microbiota resulted in cell-specific transcriptomic changes. Furthermore, microglia transcriptomes were preferentially influenced, which could be effectively reversed by microbial colonization. Significantly, the gut microbiome modulated the mutual transformation of microglial subpopulations in the two regions. Cross-species analysis showed that the transcriptome changes of these microglial subpopulations were mainly associated with Alzheimer's disease (AD) and major depressive disorder (MDD), which were further supported by animal behavioral tests. Our findings demonstrate that gut microbiota mainly modulate the mutual transformation of microglial subtypes, which may lead to new insights into the pathogenesis of AD and MDD."

基金机构："National Key R&D Program of China [2017YFA0505700]; Projects of International Cooperation and Exchanges NSFC [81820108015]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019PT320002]; Natural Science Foundation Project of China [81971296, 82171523, 82101596]; Chongqing Science & Technology Commission [cstc 2019 jcyjjqX0009]; China Postdoctoral Science Foundation [2020TQ0393, 2021TQ0396, 2021MD703928, 2021M693926]; Chongqing Talents Plan for Young Talents [CQYC202105017]; State University of New York (SUNY) Upstate Medical University"

基金资助正文："This work was supported by the National Key R & D Program of China (2017YFA0505700), Projects of International Cooperation and Exchanges NSFC (81820108015), Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT320002), the Natural Science Foundation Project of China (81971296, 82171523, and 82101596), Chongqing Science & Technology Commission (cstc 2019 jcyjjqX0009), China Postdoctoral Science Foundation (2020TQ0393, 2021TQ0396, 2021MD703928, 2021M693926), Chongqing Talents Plan for Young Talents (CQYC202105017) and institutional funds from the State University of New York (SUNY) Upstate Medical University. This paper is subject to the SUNY OpenAccess Polic"