Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan-Dec;14(1):2125739.
doi: 10.1080/19490976.2022.2125739.

Regulation of microglial physiology by the microbiota

James Cook  1 , Marco Prinz  1   2   3
Affiliations
Review

Regulation of microglial physiology by the microbiota

James Cook et al. Gut Microbes. 2022 Jan-Dec.

Abstract

The mammalian gut contains a large, complex community of microorganisms collectively termed the microbiota. It is increasingly appreciated that gut microbes are closely integrated into mammalian physiology, participating in metabolic symbiosis, promoting immune function and signaling to a wide variety of distant cells, including the brain, via circulating metabolites. Recent advances indicate that microglia, the brain's resident immune cells, are influenced by microbial metabolites at all stages of life, under both physiological and pathological conditions. The pathways by which microbiota regulate microglial function are therefore of interest for investigating links between neurological disorders and gut microbiome changes. In this review, we discuss the effects and mechanisms of microbiota-microglia signaling in steady state, as well as evidence for the involvement of this signaling axis in CNS pathologies.

Keywords: Microglia; development; gut-brain axis; gut-derived metabolites; microbiota; neurological disorders.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Microglial development. Microglia emerge from yolk-sac precursors and colonize the developing brain at around E9.5. Subsequently, they undergo a series of stepwise transformations, acquiring diverse developmental phenotypes as pre-microglia before maturing into adult microglia during the second or third postnatal week.
Figure 2.
Figure 2.
Microbiota-microglia interactions. (a) Microbiota are confined to the gut lumen, separated from the lamina propria by gut endothelial cells. Microbiota-derived metabolites can penetrate the endothelium and enter the bloodstream, as well as influencing local immune cells and vagal afferents. (b) Effects of microbial metabolites on microglial function under steady-state across developmental stages. Evidence suggests that microglial density, epigenetics and transcriptomics are affected by microbiota at all stages of life.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cryan JF, O’Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV, et al. The microbiota-gut-brain axis. Physiol Rev. 2019;99(4):1877–19. doi:10.1152/physrev.00018.2018. - DOI - PubMed
    1. Prinz M, Masuda T, Wheeler MA, Quintana FJ.. Microglia and central nervous system-associated macrophages-from origin to disease modulation. Annu Rev Immunol. 2021;39(1):251–277. doi:10.1146/annurev-immunol-093019-110159. - DOI - PMC - PubMed
    1. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010;330(6005):841–845. doi:10.1126/science.1194637. - DOI - PMC - PubMed
    1. Kierdorf K, Erny D, Goldmann T, Sander V, Schulz C, Perdiguero EG, Wieghofer P, Heinrich A, Riemke P, Hölscher C, et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat Neurosci. 2013;16(3):273–280. doi:10.1038/nn.3318. - DOI - PubMed
    1. Schulz C, Perdiguero EG, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SEW, Pollard JW, et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science. 2012;336(6077):86–90. doi:10.1126/science.1219179. - DOI - PubMed

Publication types

Grants and funding

. M.P. was supported by the Sobek Foundation, the Ernst-Jung Foundation, the Novo Nordisk Prize, the DFG (SFB 992, SFB1160, CRC/TRR 167 “NeuroMac”, Reinhart-Koselleck-Grant, Gottfried Wilhelm Leibniz Prize), Alzheimer Forschung Initiative e.V. (AFI) and the Ministry of Science, Research and Arts, Baden-Wuerttemberg (Sonderlinie “Neuroinflammation”). This study was supported by the DFG under Germany’s Excellence Strategy (CIBSS – EXC-2189 – Project ID390939984).