Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease.

Erny, Daniel; Dokalis, Nikolaos; Mezö, Charlotte; Castoldi, Angela; Mossad, Omar; Staszewski, Ori; Frosch, Maximilian; Villa, Matteo; Fuchs, Vidmante; Mayer, Arun; Neuber, Jana; Sosat, Janika; Tholen, Stefan; Schilling, Oliver; Vlachos, Andreas; Blank, Thomas; Gomez de Agüero, Mercedes; Macpherson, Andrew J; Pearce, Edward J and Prinz, Marco (2021). Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease. Cell metabolism, 33(11), 2260-2276.e7. Elsevier 10.1016/j.cmet.2021.10.010

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As tissue macrophages of the central nervous system (CNS), microglia constitute the pivotal immune cells of this organ. Microglial features are strongly dependent on environmental cues such as commensal microbiota. Gut bacteria are known to continuously modulate microglia maturation and function by the production of short-chain fatty acids (SCFAs). However, the precise mechanism of this crosstalk is unknown. Here we determined that the immature phenotype of microglia from germ-free (GF) mice is epigenetically imprinted by H3K4me3 and H3K9ac on metabolic genes associated with substantial functional alterations including increased mitochondrial mass and specific respiratory chain dysfunctions. We identified acetate as the essential microbiome-derived SCFA driving microglia maturation and regulating the homeostatic metabolic state, and further showed that it is able to modulate microglial phagocytosis and disease progression during neurodegeneration. These findings indicate that acetate is an essential bacteria-derived molecule driving metabolic pathways and functions of microglia during health and perturbation.

Item Type:

 Journal Article (Original Article)

Division/Institute:

 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

UniBE Contributor:

 Gomez de Agüero Tamargo, Maria de la Mercedes, Macpherson, Andrew

Subjects:

 600 Technology > 610 Medicine & health

ISSN:

 1932-7420

Publisher:

 Elsevier

Language:

 English

Submitter:

 Rahel Fuhrer

Date Deposited:

 13 Jan 2022 10:18

Last Modified:

 05 Dec 2022 15:56

Publisher DOI:

 10.1016/j.cmet.2021.10.010

PubMed ID:

 34731656

Uncontrolled Keywords:

 Alzheimer’s disease SCFA acetate germ-free metabolism microbiota microglia mitochondria respiratory chain

BORIS DOI:

 10.48350/162376

URI:

 https://boris.unibe.ch/id/eprint/162376

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