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@ARTICLE{Colombo:154828,
      author       = {Colombo, Alessio Vittorio and Sadler, Rebecca Katie and
                      Llovera, Gemma and Singh, Vikramjeet and Roth, Stefan and
                      Heindl, Steffanie and Sebastian Monasor, Laura and
                      Verhoeven, Aswin and Peters, Finn and Parhizkar, Samira and
                      Kamp, Frits and Gomez de Aguero, Mercedes and MacPherson,
                      Andrew J and Winkler, Edith and Herms, Jochen and Benakis,
                      Corinne and Dichgans, Martin and Steiner, Harald and Giera,
                      Martin and Haass, Christian and Tahirovic, Sabina and Liesz,
                      Arthur},
      title        = {{M}icrobiota-derived short chain fatty acids modulate
                      microglia and promote {A}β plaque deposition},
      journal      = {eLife},
      volume       = {10},
      issn         = {2050-084X},
      address      = {Cambridge},
      publisher    = {eLife Sciences Publications},
      reportid     = {DZNE-2021-00406},
      pages        = {e59826},
      year         = {2021},
      abstract     = {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.},
      keywords     = {Alzheimer Disease: metabolism / Animals / Fatty Acids,
                      Volatile: metabolism / Female / Gastrointestinal Microbiome
                      / Male / Mice / Microglia: metabolism / Plaque, Amyloid:
                      metabolism / Specific Pathogen-Free Organisms},
      cin          = {AG Tahirovic / AG Steiner / AG Herms / AG Haass},
      ddc          = {600},
      cid          = {I:(DE-2719)1140003 / I:(DE-2719)1110000-1 /
                      I:(DE-2719)1110001 / I:(DE-2719)1110007},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33845942},
      pubmed       = {33845942},
      pmc          = {pmc:PMC8043748},
      doi          = {10.7554/eLife.59826},
      url          = {https://pub.dzne.de/record/154828},
}