Author response: Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition [peer_review]

Alessio Vittorio Colombo, Rebecca Katie Sadler, Gemma Llovera, Vikramjeet Singh, Stefan Roth, Steffanie Heindl, Laura Sebastian Monasor, Aswin Verhoeven, Finn Peters, Samira Parhizkar, Frits Kamp, Mercedes Gomez de Aguero (+10 others)
2021 unpublished
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 Ab deposition. Germ-free (GF) AD mice exhibit a substantially reduced Ab plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice
more » ... d the Ab 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 Ab plaques upon SCFA supplementation, microglia contained less intracellular Ab. Taken together, our results demonstrate that microbiota-derived SCFA are critical mediators along the gut-brain axis which promote Ab deposition likely via modulation of the microglial phenotype. Colombo et al. eLife 2021;10:e59826.
doi:10.7554/elife.59826.sa2 fatcat:yu4y7pkt6fdg3iuldd34ygby24