Microbiome–microglia connections via the gut–brain axis
Microglia, the resident immune cells in the brain, are essential for modulating neurogenesis, influencing synaptic remodeling, and regulating neuroinflammation by surveying the brain microenvironment. Microglial dysfunction has been implicated in the onset and progression of several neurodevelopmental and neurodegenerative diseases; however, the multitude of factors and signals influencing microglial activity have not been fully elucidated. Microglia not only respond to local signals within the brain but also receive input from the periphery, including the gastrointestinal (GI) tract. Recent preclinical findings suggest that the gut microbiome plays a pivotal role in regulating microglial maturation and function, and altered microbial community composition has been reported in neurological disorders with known microglial involvement in humans. Collectively, these findings suggest that bidirectional crosstalk between the gut and the brain may influence disease pathogenesis. Herein, we discuss recent studies showing a role for the gut microbiome in modulating microglial development and function in homeostatic and disease conditions and highlight possible future research to develop novel microbial treatments for disorders of the brain.
© 2018 Abdel-Haq et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http:// www .rupress .org/ terms/ ). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). Submitted: 29 April 2018; Revision received 8 July 2018; Accepted: 3 October 2018; Published Online: 1 November, 2018. We would like to thank members of the Mazmanian and Glass laboratory for their critical review of this manuscript and thoughtful insight and discussion. R. Abdel-Haq is supported by the U.S. Department of Defense and the Donna and Benjamin M. Rosen Bioengineering Center. Related work in the Glass laboratory is funded by the National Institutes of Health (grants AG057706 and NS096170). Related work in the Mazmanian laboratory is funded by the Heritage Medical Research Institute, the Simons Foundation (grant 322839), the U.S. Department of Defense (PD160030), and the National Institutes of Health (grants MH100556 and NS085910) to S.K. Mazmanian. The authors declare no competing financial interests. Author contributions: R. Abdel-Haq wrote the manuscript with support from J.C.M. Schlachetzki. J.C.M. Schlachetzki and C.K. Glass critically reviewed and edited the manuscript. S.K. Mazmanian contributed to the conception and design of the manuscript. All authors reviewed the manuscript before submission.
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