Parkinson’s Gut Connection
Neurodegenerative diseases are the leading cause of morbidity, mortality and disability along with conditions like diabetes and blood pressure. Out of many neurodegenerative diseases, Parkinson is one of the most widely spread condition affecting people mainly in their mid age ranging from 60 years or older. The actual pathogenesis of the disease starts long back when the person is in his/her 30’s or 40’s. The classic symptoms of Parkinson’s include tremor, slowed movements called as bradykinesia, rigid muscles, impaired posture and balance, speech and writing difficulty.
The earliest evidence suggests that the gut might be involved in Parkinson emerged more than 200 years back. While most of us recognize Parkinson as the disease of the brain which affects nerve cells deeply present in brain such as basal ganglia and substania nigra, primarily involved in the production of an essential neurotransmitter called as Dopamine which is responsible for relaying communication between different brain parts crucial for smooth muscle movements and proper nerve functioning. Scientists have found gut to be linked with the development of Parkinson disease. Physicians have observed constipation as one of the most common symptoms of Parkinson’s, appearing in around half of the individuals diagnosed with the condition and often preceded by the onset of movement- related impairments.
There is accumulation of alpha synuclein called as lewy bodies in the brain which over time leads to major loss of neurons in brain responsible for dopamine production. Scientists have discovered in the post- mortem samples of Parkinson patients, lewy bodies i.e. the clumps of alpha synuclein appeared both in brain and gastrointestinal nervous system suggesting gut’s connection with the onset of Parkinson’s.
Scientist are still unclear about the exact role of gut in the pathogenesis of Parkinson but there’s a growing body of evidence and hypothesis suggesting gut’s connection with the brain and how changes in gut can significantly affect brain and nervous system health. Indeed, this research forces us to be more conscious about our gastrointestinal health and pay utmost attention to any changes occurring in GI because it is said that if a person’s gut is healthy and if they do not suffer from any significant GI discomforts that will surely eliminate major health problems occurring later in life. The main question here is, How changes in intestine drives neurodenegeneration in the brain? Some studies propose that aggregates of alpha synuclein move from intestines to the gut via the vagus nerve, some other suggest that gut influences brain through inflammation or products of bacterial breakdown stimulates activity along this way.
The Gut- Brain Bridge
The gut could be possibly affecting the brain through the vagus nerve which is a bundle of fibers that originates from the brain stem and innervates major abdominal organs such as stomach, esophagus and most of the intestinal tract including the gut, the primary route through which pathological triggers of Parkinson’s travel through the gastrointestinal tract to the brain.
In one study conducted, it was found out that the rodents which were injected alpha synuclein transversed from vagus into the brain and gets deposited over there affecting prominent nerve cells responsible for the production of dopamine. Now, one prominent question arises here is why does the protein accumulate in gut in the first place?
Few research suggests that the possibility of alpha synuclein appearing in the gut could be to help intestines fight off the pathogens, indicating that alpha synuclein can potentially attract and activate immune cells to elicit immune response. When we eat, there is a high possibility of harmful microbes entering the body which in turn enters intestine, and are responsible for triggering the buildup of alpha synuclein in intestines which is essentially produced as one of the defending mechanism of immune system. The misfolded alpha synuclein begin to accumulate in the enteric nerves decade before the appearance of neurological symptoms. One misfolded protein triggers misfolding of other immediate proteins which eventually leads to the formation of large chunks of defective and harmful proteins travelling from GI to the brain.
The human microbiome i.e. the totality of good microorganism present in human gut which assist body in so many processes has been the area of interest among the Parkinson’s researchers. A number of studies suggest that the people with Parkinson harbor a unique composition of gut microbes.
One study suggests that these microbes act through the metabolites they produce such as long chain fatty acids. In one of the experiment conducted on mouse, it was demonstrated that these molecules activate microglia cells, the immune cells of the brain.
Does Gut Inflammation affect Brain?
Another study conducted on 144,018 individuals showed that the gut inflammation, possibly from gut microbes could affect brain and give rise to Parkinson. Study revealed that the incidence of Parkinson was 28% higher in individuals suffering from inflammatory bowel disease and the people who received drugs to reduce inflammation — tumor necrosis factor (TNF) inhibitors- the incidence of neurodegenerative disease dropped by 78%.
Intestinal inflammation could give rise to Parkinson in several ways :
One of the many proposed possibility is that chronically inflamed gut might elevate alpha synuclein level locally in the intestine or it may give rise to inflammation through the body which in turn affects the permeability of blood brain barrier which allows harmful protein to get inside the brain easily. Or maybe increased levels of circulating cytokines that promotes inflammation and simply any change in the gut microbiome can influence gut inflammation which is then transversed to other body organs including brain.
Research is still in progress as to understand the exact role of TNF-inhibtors on both brain and GI, that whether they exert protective effect only to individuals with IBD or they actually protect brain by reducing inflammation. Other group of scientists are also investigating the role of antiinflammatory drugs used in conditions like rheumatoid arthritis and psoriasis on brain’s health.
A lot of investigation still needs to be done and infact going on the gut- brain relation and how treatments catering to the gastrointestinal tract such as constipation affects brain’s health, the scientists hope that targeting early gut pathology affects or restore the central nervous system health.
