| Autor: |
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, Andrew J MacPherson, Edith Winkler, Jochen Herms, Corinne Benakis, Martin Dichgans, Harald Steiner, Martin Giera, Christian Haass, Sabina Tahirovic, Arthur Liesz |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.59826 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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