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Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition
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 whi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043748/ https://www.ncbi.nlm.nih.gov/pubmed/33845942 http://dx.doi.org/10.7554/eLife.59826 |
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author | Colombo, Alessio Vittorio Sadler, Rebecca Katie Llovera, Gemma Singh, Vikramjeet Roth, Stefan Heindl, Steffanie Sebastian Monasor, Laura Verhoeven, Aswin Peters, Finn Parhizkar, Samira Kamp, Frits Gomez de Aguero, Mercedes MacPherson, Andrew J Winkler, Edith Herms, Jochen Benakis, Corinne Dichgans, Martin Steiner, Harald Giera, Martin Haass, Christian Tahirovic, Sabina Liesz, Arthur |
author_facet | Colombo, Alessio Vittorio Sadler, Rebecca Katie Llovera, Gemma Singh, Vikramjeet Roth, Stefan Heindl, Steffanie Sebastian Monasor, Laura Verhoeven, Aswin Peters, Finn Parhizkar, Samira Kamp, Frits Gomez de Aguero, Mercedes MacPherson, Andrew J Winkler, Edith Herms, Jochen Benakis, Corinne Dichgans, Martin Steiner, Harald Giera, Martin Haass, Christian Tahirovic, Sabina Liesz, Arthur |
author_sort | Colombo, Alessio Vittorio |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8043748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-80437482021-04-21 Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition Colombo, Alessio Vittorio Sadler, Rebecca Katie Llovera, Gemma Singh, Vikramjeet Roth, Stefan Heindl, Steffanie Sebastian Monasor, Laura Verhoeven, Aswin Peters, Finn Parhizkar, Samira Kamp, Frits Gomez de Aguero, Mercedes MacPherson, Andrew J Winkler, Edith Herms, Jochen Benakis, Corinne Dichgans, Martin Steiner, Harald Giera, Martin Haass, Christian Tahirovic, Sabina Liesz, Arthur eLife Immunology and Inflammation 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. eLife Sciences Publications, Ltd 2021-04-13 /pmc/articles/PMC8043748/ /pubmed/33845942 http://dx.doi.org/10.7554/eLife.59826 Text en © 2021, Colombo et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Colombo, Alessio Vittorio Sadler, Rebecca Katie Llovera, Gemma Singh, Vikramjeet Roth, Stefan Heindl, Steffanie Sebastian Monasor, Laura Verhoeven, Aswin Peters, Finn Parhizkar, Samira Kamp, Frits Gomez de Aguero, Mercedes MacPherson, Andrew J Winkler, Edith Herms, Jochen Benakis, Corinne Dichgans, Martin Steiner, Harald Giera, Martin Haass, Christian Tahirovic, Sabina Liesz, Arthur Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition |
title | Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition |
title_full | Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition |
title_fullStr | Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition |
title_full_unstemmed | Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition |
title_short | Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition |
title_sort | microbiota-derived short chain fatty acids modulate microglia and promote aβ plaque deposition |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043748/ https://www.ncbi.nlm.nih.gov/pubmed/33845942 http://dx.doi.org/10.7554/eLife.59826 |
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