Home > Publications Database > Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition > print

001     154828
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024 7 _ |a 10.7554/eLife.59826
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100 1 _ |a Colombo, Alessio Vittorio
|0 P:(DE-2719)2340744
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245 _ _ |a Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition
260 _ _ |a Cambridge
|c 2021
|b eLife Sciences Publications
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520 _ _ |a 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.
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650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Fatty Acids, Volatile: metabolism
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Gastrointestinal Microbiome
|2 MeSH
650 _ 2 |a Male
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650 _ 2 |a Mice
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650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Plaque, Amyloid: metabolism
|2 MeSH
650 _ 2 |a Specific Pathogen-Free Organisms
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700 1 _ |a Sadler, Rebecca Katie
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700 1 _ |a Llovera, Gemma
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700 1 _ |a Singh, Vikramjeet
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700 1 _ |a Roth, Stefan
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700 1 _ |a Heindl, Steffanie
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700 1 _ |a Sebastian Monasor, Laura
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700 1 _ |a Peters, Finn
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700 1 _ |a Kamp, Frits
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700 1 _ |a Gomez de Aguero, Mercedes
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700 1 _ |a MacPherson, Andrew J
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700 1 _ |a Herms, Jochen
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700 1 _ |a Benakis, Corinne
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700 1 _ |a Dichgans, Martin
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700 1 _ |a Steiner, Harald
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700 1 _ |a Giera, Martin
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700 1 _ |a Haass, Christian
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700 1 _ |a Tahirovic, Sabina
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700 1 _ |a Liesz, Arthur
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773 _ _ |a 10.7554/eLife.59826
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856 4 _ |u https://elifesciences.org/articles/59826
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