Parkinson's disease and gut-brain axis
[5][7] The neuropathological hallmarks of PD include the loss of dopaminergic neurons in the substantia nigra pars compacta region of the brain (shown in figure) and the presence of aggregated alpha-synuclein.
[2] Under physiological conditions, alpha-synuclein, a protein encoded by the SNCA gene, is found at the synapses of neurons, where it regulates synaptic signaling and plasticity by modulating the release of neurotransmitters.
[4] [2] It is hypothesized to propagate in a prion-like manner, spreading within and between other cells, eventually leading to neurodegeneration, which is seen in the illustration with the loss of dopaminergic neurons.
[16][6][8] In the upper GI tract, dysphagia is a swallowing impairment that results in inadequate mastication (chewing), body mass index below than 20, weight loss and malnutrition.
[13] Small intestinal bacterial overgrowth (SIBO): results in diarrhea, abdominal discomfort, bloating and can lead to absorption issues of PD medications.
[13] In the lower GI tract, constipation is characterized by straining during defecation or having less than 3 bowel movements per week, which occurs in 40-50% of PD patients.
[12] [13] This was further supported by the decrease in PD risk with truncal vagotomy, a procedure that involves the cutting of the fibers in the vagus nerve that connect to the stomach.
[8][13] The microbiota, located throughout the GI tract, contains thousands of different microbial species that have evolved to form a mutualistic and symbiotic relationship with the host.
Genome-wide association studies (GWAS) has linked several autosomal dominant (SNCA, LRRK2, GBA) and recessive (DJ-1, PINK1, PARK7, Parkin) mutations to the development of PD.
[3] This further suggests the involvement of other factors, such as the environment, in the increased vulnerability of developing the disease and in clinical presentation of symptoms of genetic forms of PD.
[3] There are many factors that contribute to this decline, such as the immune system, changes in lifestyle, the environment, medications, other diseases, and organ dysfunction.
[6] In other animal studies, exposure to pesticide rotenone resulted in alpha synuclein being released from enteric neurons into the extracellular matrix.
[6] In vitro studies also showed that secreted alpha-synuclein can be undergo transneuronal retrograde movement, where it can be taken up by other neurons or non-neuronal cell types.
[6] Food: There are many epidemiological studies that demonstrate the significant impact of diet on the onset and exacerbation of PD through its influence on the composition of the gut microbiota.
[18] Versus Western diets that result in a lower abundance of [clarification needed] Fluids: Caffeine drinkers and smokers have a decreased risk of PD, by 60% and 30%, respectively, potentially through the modulation of the gut-brain axis.
[11] Flavonoids (found in tea, red wine, oranges, apples and berry fruits) have antioxidant and antimicrobial properties and have been linked to a lower risk of PD.
