Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer’s disease-type beta-amyloid neuropathological mechanisms

Lap Ho, Kenjiro Ono, Mayumi Tsuji, Paolo Mazzola, Risham Singh, Giulio M. Pasinetti

Research output: Contribution to journalArticlepeer-review

282 Scopus citations

Abstract

Background: Dietary fibers are metabolized by gastrointestinal (GI) bacteria into short-chain fatty acids (SCFAs). We investigated the potential role of these SCFAs in β-amyloid (Aβ) mediated pathological processes that play key roles in Alzheimer’s disease (AD) pathogenesis. Research design and methods: Multiple complementary assays were used to investigate individual SCFAs for their dose-responsive effects in interfering with the assembly of Aβß1-40 and Aβ1-42 peptides into soluble neurotoxic Aβ aggregates. Results: We found that several select SCFAs are capable of potently inhibiting Aβ aggregations, in vitro. Conclusion: Our studies support the hypothesis that intestinal microbiota may help protect against AD, in part, by supporting the generation of select SCFAs, which interfere with the formation of toxic soluble Aβ aggregates.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalExpert Review of Neurotherapeutics
Volume18
Issue number1
DOIs
StatePublished - 2 Jan 2018

Keywords

  • Alzheimer’s disease
  • beta-amyloid (Aβ)
  • fibrils
  • microbial
  • microbiome
  • microbiota
  • neurodegeneration
  • protein misfolding

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