Souradip Mallick, National Institute of Technology, Rourkela
Parkinson’s disease (PD) affects at a rapid rate almost doubled within one decade. PD is a progressive degenerative disease that mainly affects the brain, the peripheral nervous system, and the gastrointestinal tract, causing progressive movement disorders, gastrointestinal and autonomic dysfunction, sleep disorders, and cognitive impairment. There is no prevention, cure, or treatment known to cure this disease. There is a connection between PD and the gastrointestinal tract, and hence with the gut microbiome.
Studies on PD have consistently found altered gut microbiome, with depletion of short-chain fatty acid (SCFA) producing bacteria, and enrichment of Lactobacillus and Bifidobacterium. Recently a microbiome-wide association study in connection with PD was reported where Lactobacillus and Bifidobacterium were robustly confirmed. Along with these two, a significant increase was also detected for Corynebacterium, Porphyromonas, and Prevotella. These are commensal bacteria normally found in low abundance in the gut, but they can cause infections in opportunistic situations such as in the case of a compromised immune system. An overabundance of opportunistic pathogens in the PD gut was of prime interest. Misfolded alpha-synuclein is a key pathological protein in Parkinson’s disease (PD). This alpha-synuclein is formed in enteric neurons during the onset of the disease and then propagates in a prion-like manner from the gut to the brain in animal models. The gene that encodes alpha-synuclein is SNCA. SNCA gene multiplication results in drastic overexpression of alpha-synuclein and causes Mendelian autosomal dominant PD.
Hence the host genotype at the alpha-synuclein locus influenced the enormous growing rate of opportunistic pathogens in the PD gut, and the different variants modulate alpha-synuclein expression. This modulation proved that there is a significant interaction between genetic factors in the human genome and the dysbiosis of the gut microbiome in PD.
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Source – Zachary D. Wallen, William J. Stone, Stewart A. Factor, Eric Molho, Cyrus P. Zabetian, David G. Standaert and Haydeh Payami; Human-genome gut-microbiome interaction in Parkinson’s disease; January 22, 2021; https://doi.org/10.1101/2021.01.21.427679.
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