Journal of Alzheimer's Disease
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Home > Geographical Distribution and Diversity of Gut Microbial NADH:Ubiquinone Oxidoreductase Sequence Associated with Alzheimer's Disease.

TitleGeographical Distribution and Diversity of Gut Microbial NADH:Ubiquinone Oxidoreductase Sequence Associated with Alzheimer's Disease.
Publication TypeJournal Article
Year of Publication2018
AuthorsPaley, EL, Merkulova-Rainon, T, Faynboym, A, Shestopalov, VI, Aksenoff, I
JournalJ Alzheimers Dis
Volume61
Issue4
Pagination1531-1540
Date Published2018
ISSN1875-8908
KeywordsAdult, Aged, Aged, 80 and over, Alzheimer Disease, Anti-Bacterial Agents, Biological Transport, DNA Primers, Electron Transport Complex I, Feces, Female, Gastrointestinal Microbiome, Geography, Host-Pathogen Interactions, Humans, Male, Middle Aged, Sequence Analysis, DNA, Young Adult
Abstract

Earlier we reported induction of neurotoxicity and neurodegeneration by tryptophan metabolites that link the metabolic alterations to Alzheimer's disease (AD). Tryptophan is a product of Shikimate pathway (SP). Human cells lack SP, which is found in human gut bacteria exclusively using SP to produce aromatic amino acids (AAA). This study is a first attempt toward gene-targeted analysis of human gut microbiota in AD fecal samples. The oligonucleotide primers newly-designed for this work target SP-AAA in environmental bacteria associated with human activity. Using polymerase chain reaction (PCR), we found unique gut bacterial sequence in most AD patients (18 of 20), albeit rarely in controls (1 of 13). Cloning and sequencing AD-associated PCR products (ADPP) enables identification of Na(+)-transporting NADH: Ubiquinone reductase (NQR) in Clostridium sp. The ADPP of unrelated AD patients possess near identical sequences. NQR substrate, ubiquinone is a SP product and human neuroprotectant. A deficit in ubiquinone has been determined in a number of neuromuscular and neurodegenerative disorders. Antibacterial therapy prompted an ADPP reduction in an ADPP-positive control person who was later diagnosed with AD-dementia. We explored the gut microbiome databases and uncovered a sequence similarity (up to 97%) between ADPP and some healthy individuals from different geographical locations. Importantly, our main finding of the significant difference in the gut microbial genotypes between the AD and control human populations is a breakthrough.

DOI10.3233/JAD-170764
Alternate JournalJ. Alzheimers Dis.
PubMed ID29376868
Grant ListP30 EY014801 / EY / NEI NIH HHS / United States
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Source URL: https://www.j-alz.com/content/geographical-distribution-and-diversity-gut-microbial-nadhubiquinone-oxidoreductase-sequence