Geographical Distribution and Diversity of Gut Microbial NADH:Ubiquinone Oxidoreductase Sequence Associated with Alzheimer’s Disease

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.

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

“…specific of patients with AD 63. These sequences encoded for NADH:ubiquinone oxidoreductase, an enzyme involved in aromatic amino acid production 63.…”

“…specific of patients with AD 63. These sequences encoded for NADH:ubiquinone oxidoreductase, an enzyme involved in aromatic amino acid production 63. High levels of these amino acids in the brain may induce cell death and neurodegeneration, and thus, the gut microbiota functionality may directly influence the AD physiopathology through this pathway.…”

Exercise, the Gut Microbiome, and Frailty

“…60) According to the 16S rRNA microbial profile, the gut microbiome diversity is significantly lower in people with Clostridium clustering. 60,61) Cyanobacteria within the gut microbiota can synthesize neurotoxins such as saxitoxin and alpha-anatoxin. 62) Moreover, Citrobacter, Escherichia coli, Klebsiella, Mycobacteria, Pseudomonas, Streptococcus, Streptomyces, Staphylococcus, Salmonella, and Bacillus spp.…”

Towards an Integrative Understanding of tRNA Aminoacylation–Diet–Host–Gut Microbiome Interactions in Neurodegeneration

“…Tryptamine is increased under sporulating conditions in wheat pathogenic fungus Stagonospora nodorum [ 17 ]. The gut microbiome is altered in AD patients [ 18 , 19 ]. The gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals [ 19 ].…”

“…The gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals [ 19 ]. Our study revealed the gut bacterial sequence specific for AD patients [ 18 ]. This sequence belongs to the gene encoding Na(+)-transporting NADH: Ubiquinone reductase (NQR) while both the NQR substrate ubiquinone and Tryptophan are the products of Shikimate pathway.…”