Does the Gut Biome Control Parkinson’ s Disease?
by Adriana Mulet Miranda, BS, & Steven Lippmann, MD
Parkinson’ s Disease( PD) is a debilitating neurodegenerative disorder of the central nervous system that affects about 3 % of people who are 65 years of age and 5 % of those who are over 85 years old. 1 PD can result from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain that controls movement and coordination. Around 90 % of those with PD suffer from sporadic variants, which suggests that there is no known cause or familial history of this disease. 1 However, the other 10 % are a genetic version. This can occur in an autosomal recessive form, where those who are under age 40 are diagnosed, and an autosomal dominant version confers pathology to the rest. Research attributes PD’ s etiology to the aggregation of ⍺-synuclein cytoplasmic inclusions, also called Lewy bodies. This ⍺-synuclein is a protein in the central nervous system whose function is unknown, but is thought to involve the regulation of synaptic vesicle tracking and neurotransmitter release. 1
The cause of ⍺-synuclein aggregation is unknown. There is a relationship between gut bacteria and the brain, the gut-brain axis. 2 This pathway hypothesizes that through dysbiosis, which is the accumulation of pathological bacteria, proteins that affect membrane permeability accumulate and leak out of the gut. From there, through the bloodstream, they diminish the blood-brain barrier. This includes ⍺-synuclein going through the vagus nerve into the brain, resulting in accumulation.
Amyloids are highly ordered cross-β sheet proteins. Amyloid aggregation is based on these sheets comprising an infinitely repeating pattern within protein folds. Cross β-sheets grow by accumulating other amyloid proteins that repetitively augments their actions. 3 Specifically, ⍺-synuclein has a region called the non-amyloid component, where it promotes amyloid structure formation. Therefore, these amyloids often aggregate, leading to many diseases including Parkinson’ s Disease.
Calprotectin and zonulin are proteins that attenuate infections and loosen gut cell junctions. 4 However, with dysbiosis, they accumulate and increase membrane permeability through inflammation. To strengthen this correlation, levels of fecal and serum calprotectin and zonulin were measured in patients with PD and healthy controls. 4 Reportedly, these protein levels were elevated in the subject’ s feces and also in the serum. High levels indicate that these concentrations of proteins in the bloodstream are congruent with the gut-brain axis theory. Once the specimens were collected, the levels of calprotectin and zonulin were measured through enzyme-linked immunoabsorbent assays. 4 Even with a small sample size, this study indicated that patients with PD have a higher percentage of these proteins, above the normal value for healthy controls. This suggests an association between PD and serum and / or fecal markers of inflammation and permeability. Since these proteins aggregate during dysbiosis, the brain and the gut are connected, with pathology beginning in the( continued on page 30)
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