TY - JOUR
T1 - Geographical distribution and diversity of gut microbial NADH
T2 - Ubiquinone oxidoreductase sequence associated with Alzheimer's disease
AU - Paley, Elena L.
AU - Merkulova-Rainon, Tatiana
AU - Faynboym, Aleksandr
AU - Shestopalov, Valery I.
AU - Aksenoff, Igor
N1 - Funding Information:
This research was funded by Art Medicus PLLC, Yonkers, NY and in part (DNA cloning and sequencing) by the National Eye Institute–National Institutes of Health Grants EY02238 and P30 EY014801 to
PY - 2018
Y1 - 2018
N2 - 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 the Shikimate pathway (SP).Humancells lackSP, 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 mostADpatients (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.
AB - 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 the Shikimate pathway (SP).Humancells lackSP, 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 mostADpatients (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.
KW - Alzheimer's disease
KW - Bacterial enzyme sequence
KW - Environmental stool samples
KW - Human gut microbiota
KW - PCR testing
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U2 - 10.3233/JAD-170764
DO - 10.3233/JAD-170764
M3 - Article
C2 - 29376868
AN - SCOPUS:85044606950
VL - 61
SP - 1531
EP - 1540
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 4
ER -