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000154828 1001_ $$0P:(DE-2719)2340744$$aColombo, Alessio Vittorio$$b0$$eFirst author$$udzne
000154828 245__ $$aMicrobiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition
000154828 260__ $$aCambridge$$beLife Sciences Publications$$c2021
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000154828 520__ $$aPrevious studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, the mechanisms of microbiome–brain interaction in AD were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as microbial metabolites which promote Aβ deposition. Germ-free (GF) AD mice exhibit a substantially reduced Aβ plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice increased the Aβ plaque load to levels of conventionally colonized (specific pathogen-free [SPF]) animals and SCFA supplementation to SPF mice even further exacerbated plaque load. This was accompanied by the pronounced alterations in microglial transcriptomic profile, including upregulation of ApoE. Despite increased microglial recruitment to Aβ plaques upon SCFA supplementation, microglia contained less intracellular Aβ. Taken together, our results demonstrate that microbiota-derived SCFA are critical mediators along the gut-brain axis which promote Aβ deposition likely via modulation of the microglial phenotype.
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000154828 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000154828 650_2 $$2MeSH$$aAnimals
000154828 650_2 $$2MeSH$$aFatty Acids, Volatile: metabolism
000154828 650_2 $$2MeSH$$aFemale
000154828 650_2 $$2MeSH$$aGastrointestinal Microbiome
000154828 650_2 $$2MeSH$$aMale
000154828 650_2 $$2MeSH$$aMice
000154828 650_2 $$2MeSH$$aMicroglia: metabolism
000154828 650_2 $$2MeSH$$aPlaque, Amyloid: metabolism
000154828 650_2 $$2MeSH$$aSpecific Pathogen-Free Organisms
000154828 7001_ $$aSadler, Rebecca Katie$$b1
000154828 7001_ $$aLlovera, Gemma$$b2
000154828 7001_ $$aSingh, Vikramjeet$$b3
000154828 7001_ $$aRoth, Stefan$$b4
000154828 7001_ $$00000-0003-3576-2702$$aHeindl, Steffanie$$b5
000154828 7001_ $$0P:(DE-2719)2812269$$aSebastian Monasor, Laura$$b6$$udzne
000154828 7001_ $$aVerhoeven, Aswin$$b7
000154828 7001_ $$0P:(DE-2719)2810458$$aPeters, Finn$$b8$$udzne
000154828 7001_ $$aParhizkar, Samira$$b9
000154828 7001_ $$0P:(DE-HGF)0$$aKamp, Frits$$b10
000154828 7001_ $$00000-0002-7132-290X$$aGomez de Aguero, Mercedes$$b11
000154828 7001_ $$aMacPherson, Andrew J$$b12
000154828 7001_ $$0P:(DE-2719)9000349$$aWinkler, Edith$$b13$$udzne
000154828 7001_ $$0P:(DE-2719)2810441$$aHerms, Jochen$$b14$$udzne
000154828 7001_ $$aBenakis, Corinne$$b15
000154828 7001_ $$0P:(DE-HGF)0$$aDichgans, Martin$$b16
000154828 7001_ $$0P:(DE-2719)2000023$$aSteiner, Harald$$b17$$udzne
000154828 7001_ $$00000-0003-1684-1894$$aGiera, Martin$$b18
000154828 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b19$$udzne
000154828 7001_ $$0P:(DE-2719)2442036$$aTahirovic, Sabina$$b20$$eCorresponding author$$udzne
000154828 7001_ $$00000-0002-9069-2594$$aLiesz, Arthur$$b21$$eCorresponding author
000154828 773__ $$0PERI:(DE-600)2687154-3$$a10.7554/eLife.59826$$gVol. 10, p. e59826$$pe59826$$teLife$$v10$$x2050-084X$$y2021
000154828 8564_ $$uhttps://elifesciences.org/articles/59826
000154828 8564_ $$uhttps://pub.dzne.de/record/154828/files/7827.pdf$$yOpenAccess
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