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

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.

KEYWORDS:

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

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This study was supported in part by Grant Number P50 AT008661-01 from the NCCIH and the ODS. GM Pasinetti holds a VA Career Scientist Award. The authors acknowledge that the contents of this study do not represent the views of the NCCIH, the ODS, the NIH, the U.S. Department of Veterans Affairs, or the United States Government.