TY  - JOUR
AU  - Colombo, Alessio Vittorio
AU  - Sadler, Rebecca Katie
AU  - Llovera, Gemma
AU  - Singh, Vikramjeet
AU  - Roth, Stefan
AU  - Heindl, Steffanie
AU  - Sebastian Monasor, Laura
AU  - Verhoeven, Aswin
AU  - Peters, Finn
AU  - Parhizkar, Samira
AU  - Kamp, Frits
AU  - Gomez de Aguero, Mercedes
AU  - MacPherson, Andrew J
AU  - Winkler, Edith
AU  - Herms, Jochen
AU  - Benakis, Corinne
AU  - Dichgans, Martin
AU  - Steiner, Harald
AU  - Giera, Martin
AU  - Haass, Christian
AU  - Tahirovic, Sabina
AU  - Liesz, Arthur
TI  - Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition
JO  - eLife
VL  - 10
SN  - 2050-084X
CY  - Cambridge
PB  - eLife Sciences Publications
M1  - DZNE-2021-00406
SP  - e59826
PY  - 2021
AB  - Previous 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.
KW  - Alzheimer Disease: metabolism
KW  - Animals
KW  - Fatty Acids, Volatile: metabolism
KW  - Female
KW  - Gastrointestinal Microbiome
KW  - Male
KW  - Mice
KW  - Microglia: metabolism
KW  - Plaque, Amyloid: metabolism
KW  - Specific Pathogen-Free Organisms
LB  - PUB:(DE-HGF)16
C6  - pmid:33845942
C6  - 33845942
C2  - pmc:PMC8043748
DO  - DOI:10.7554/eLife.59826
UR  - https://pub.dzne.de/record/154828
ER  -