Affiliations: [a] Expert Biomed, Inc. Miami, FL, USA
| [b] Stop Alzheimers Corp, Miami, FL, USA
| [c] Nova Southeastern University, Fort Lauderdale, FL, USA
| [d] Institut des Vaisseaux et du Sang, Paris, France
| [e] INSERM U965, Paris, France
| [f] Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| [g] Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL, USA
Correspondence:
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Correspondence to: Elena L. Paley, 11933 SW 271st Ter., Miami, FL 33032, USA. Tel.: +1 305 469 1010; E-mails: [email protected]; [email protected].
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 the 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.
Keywords: Alzheimer’s disease, bacterial enzyme sequence, environmental stool samples, human gut microbiota, PCR testing
