Host microbiota constantly control maturation and function of microglia in the CNS
- PMID: 26030851
- PMCID: PMC5528863
- DOI: 10.1038/nn.4030
Host microbiota constantly control maturation and function of microglia in the CNS
Abstract
As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.
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Comment in
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Go with your gut: microbiota meet microglia.Nat Neurosci. 2015 Jul;18(7):930-1. doi: 10.1038/nn.4051. Nat Neurosci. 2015. PMID: 26108718 Free PMC article.
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Gut microbiota: Microbiota and neuroimmune signalling-Metchnikoff to microglia.Nat Rev Gastroenterol Hepatol. 2015 Sep;12(9):494-6. doi: 10.1038/nrgastro.2015.127. Epub 2015 Jul 28. Nat Rev Gastroenterol Hepatol. 2015. PMID: 26215386 No abstract available.
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References
-
- Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol. 2009;27:119–145. - PubMed
-
- Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev. 2011;91:461–553. - PubMed
-
- Prinz M, Priller J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci. 2014;15:300–312. - PubMed
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