A complex gut microbiota is required for proper immune cell development and homeostasis. But what about the homeostasis of microglia — the macrophages resident in the brain? Prinz and colleagues found marked defects in the microglia from germ-free mice compared with specific pathogen free (SPF) mice: they were present in higher numbers, had an immature phenotype and morphology, and showed diminished responses to pathogen-derived products or viral infection. Temporary depletion of the intestinal microbiota of SPF mice by antibiotic treatment also impaired microglia homeostasis, and recolonization with a complex microbiota normalized microglia phenotype and function. Strikingly, exposure of germ-free mice to bacteria-derived short-chain fatty acids largely rescued the defects in microglia number and maturation. Thus, ongoing input from microbial metabolites maintains microglia homeostasis.
References
Erny, D. et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. http://dx.doi.org/10.1038/nn.4030 (2015)
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Bird, L. Bugs on the brain. Nat Rev Immunol 15, 403 (2015). https://doi.org/10.1038/nri3882
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DOI: https://doi.org/10.1038/nri3882