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Front Immunol. 2018 Oct 5;9:2325. doi: 10.3389/fimmu.2018.02325. eCollection 2018.

The Gut-Microglia Connection: Implications for Central Nervous System Diseases.

Wang Y1,2,3, Wang Z1,2,3, Wang Y4, Li F1,2,3, Jia J1,2,3, Song X1,2,3,5, Qin S1,2,3,5, Wang R1,2,3,5, Jin F1,6, Kitazato K7, Wang Y1,2,3.

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Guangzhou Jinan Biomedicine Research and Development Center, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
Key Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, China.
Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.
Key Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
College of Pharmacy, Jinan University, Guangzhou, China.
Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China.
Division of Molecular Pharmacology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.


The importance of the gut microbiome in central nervous system (CNS) diseases has long been recognized; however, research into this connection is limited, in part, owing to a lack of convincing mechanisms because the brain is a distant target of the gut. Previous studies on the brain revealed that most of the CNS diseases affected by the gut microbiome are closely associated with microglial dysfunction. Microglia, the major CNS-resident macrophages, are crucial for the immune response of the CNS against infection and injury, as well as for brain development and function. However, the current understanding of the mechanisms controlling the maturation and function of microglia is obscure, especially regarding the extrinsic factors affecting microglial function during the developmental process. The gut microflora has been shown to significantly influence microglia from before birth until adulthood, and the metabolites generated by the microbiota regulate the inflammation response mediated by microglia in the CNS; this inspired our hypothesis that microglia act as a critical mediator between the gut microbiome and CNS diseases. Herein, we highlight and discuss current findings that show the influence of host microbiome, as a crucial extrinsic factor, on microglia within the CNS. In addition, we summarize the CNS diseases associated with both the host microbiome and microglia and explore the potential pathways by which the gut bacteria influence the pathogenesis of CNS diseases. Our work is thus a comprehensive theoretical foundation for studies on the gut-microglia connection in the development of CNS diseases; and provides great potential for researchers to target pathways associated with the gut-microglia connection and overcome CNS diseases.


brain; central nervous system diseases; gut microbiome; gut-microglia connection; microglia

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