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

Background: Dietary fibers are metabolized by gastrointestinal (GI) bacteria into short-chain fatty acids (SCFAs). We investigated the potential role of these SCFAs in -amyloid (A) 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 A ss 1-40 and A1-42 peptides into soluble neurotoxic A aggregates.Results: We found that several select SCFAs are capable of potently inhibiting A 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 A aggregates.