Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition

• DOI: 10.7554/elife.59826
• Publication Date: 2021-04-13T00:01:29Z
• Authors: Alessio Vittorio ...; Rebecca Katie Sadler; Gemma Llovera; Vikramjeet Singh; Stefan Roth; Steffanie Heindl; Laura Sebastian M...; Aswin Verhoeven; Finn Peters; Samira Parhizkar; Frits Kamp; Mercedes Gomez de...; Andrew J MacPherson; Edith Winkler; Jochen Herms; Corinne Benakis; Martin Dichgans; Harald Steiner; Martin Giera; Christian Haass; Sabina Tahirovic; Arthur Liesz
• Keywords: Gut–brain axis; Proinflammatory cytokine

Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, mechanisms microbiome–brain interaction 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) mice exhibit substantially reduced plaque load and markedly SCFA plasma concentrations; conversely, supplementation to GF increased levels conventionally colonized (specific pathogen-free [SPF]) animals SPF even further exacerbated load. This was accompanied by pronounced alterations microglial transcriptomic profile, including upregulation ApoE. Despite recruitment plaques upon supplementation, microglia contained less intracellular Aβ. Taken together, our results demonstrate that are critical mediators along gut-brain axis deposition likely via modulation phenotype.