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Role of gut microbiota‐derived polyphenolic acid in attenuation of protein misfolding in neurodegeneration
Author(s) -
Pasinetti Giulio Maria,
Ho Lap Maria,
Faith Jeremiah Maria,
Ono Kenjiro Maria
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.646.23
Subject(s) - polyphenol , biochemistry , chemistry , neurodegeneration , amino acid , bacteria , gut flora , in vitro , microbial metabolism , metabolism , immune system , biology , food science , antioxidant , disease , medicine , immunology , genetics , pathology
Background There is increasing evidence supporting a protective role of intestinal microbiota against diverse medical conditions, including neurological disorders such as Alzheimer's disease (AD) by modulation, in part, of metabolic and immune responses. For example, gut bacteria metabolize soluble dietary fiber into biologically available short chain fatty acids (SCFAs) that may help modulate immune responses in the periphery and in the brain. Gut bacteria are also known for their role in converting dietary polyphenols into biologically available phenolic acids with anti‐oxidant activities. However, there is little information on the potential role of SCFAs and phenolic acids in Alzheimer's disease. The present study is designed to investigate effects of these SCFAs and phenolic acids in beta‐amyloid (Aβ)‐mediated pathologic processes that play key roles in AD pathogenesis. Methods In in vitro studies using multiple complementary assays, we investigated individual SCFA and phenolic acid that are generated by GI microbial metabolism of dietary fiber and polyphenols for their dose‐responsive effects in interfering with the assembly of Aβ peptides into neurotoxic soluble Aβ aggregates. We also investigated in vitro effects of isolated human GI bacteria in converting dietary fibers and select polyphenol products into biologically available SCFAs and phenolic acids that are effective in inhibiting Aβ aggregation. Results We found several phenolic acids that potently inhibited Aβ aggregation. We also found significant differences among GI microbiota from different healthy human donors in converting dietary polyphenols into these bioactive phenolic acids and in further metabolic degradation of these phenolic acids. Ongoing studies are investigating effects of individual SCFAs in Aβ aggregation and the efficacy of GI microbiota from different human donors in the generation (and degradation) of these SCFAs. Conclusions Intestinal microbiota may help protect AD, in part, by supporting the generation of phenolic acids and SCFAs that interferes with the formation of toxic soluble Aβ aggregates. Presence of interpersonal differences in the human gut microbiota may lead to interpersonal variation to benefit from the protective effects of dietary fiber and polyphenols in AD. Outcomes provide critical information for developing probiotics to help prevent and/or treat AD.