An unhealthy gut plays an important role in Parkinson’s disease.
Some scientists even believe that problems in the gut are the main driver of Parkinson’s disease.
For example, according to one hypothesis, alpha-synuclein (a protein found in neurons) starts to accumulate in neurons in the gut. In the form of a chain reaction, these protein aggregates start to spread upwards via nerves that connect the gut with the brain.
Whether an unhealthy gut is a main cause of Parkinson’s disease, or just drives or accelerates the disease, remains to be seen.
What is clear however, is that the gut plays an important role in Parkinson’s disease.
Some arguments for this are the following:
- Specific bacteria in the gut produce proteins, like the curli protein, which can induce the aggregation of other proteins, such as alpha-synuclein (alpha-synuclein is the main protein that accumulates in the brains of Parkinson’s disease patients) (R).
- Alpha-synuclein has a “domino” or “prion”-like effect: an aggregated/badly folded alpha-synuclein protein can induce other alpha-synuclein proteins to aggregate (clump together), causing a chain reaction that can spread through nerves and brain regions. This way, alpha-synuclein can start in the gut and spread from the gut to the brain via the nerves that connect the gut with the brain (R,R).
- Aggregates of alpha-synuclein have been found in the gut and in the nerves connecting the gut and the brain in Parkinson's patients (R), sometimes up to 8 years before the disease originates (R).
- Cutting the vagus nerve, an important nerve that connects the gut with the brain (stem), substantially reduces risk of Parkinson’s disease in mice.
- Cutting specific branches of the vagus nerve (connecting the stomach with the brain) was associated with a 40% reduced risk of Parkinson’s disease in humans according to one study (R).
- People who got their appendix removed had a 20 to 25% lower risk of Parkinson’s disease (R).
- According to Dr. Heiko Braak, alpha-synuclein aggregates already start low in the brain stem, and likely even in the gut, and then spread to higher regions, such as the substantia nigra (R).
- Parkinson’s disease seems to always spread in a specific way in the brain, starting from the midbrain regions, and then to other “higher” brain structures, like the cortex, which suggest that indeed the alpha-synuclein spreads from lower parts of the nervous centrum to higher parts, in the form of a “prion”-like chain reaction.
Fig.: According to Braak’s hypothesis, Parkinson’s disease starts in the gut (enteric) nervous system and spreads “upwards” to the brain and then from lower to higher brain regions, finally reaching the neocortex (Source: “The Prion Hypothesis in Parkinson’s Disease: Braak to the Future.” Acta Neuropathologica Communications 1. CC BY 2.5)
- Often, gastro-intestinal problems, such as constipation, precede the first symptoms of Parkinson’s disease by many years, sometimes even decades.
- In most Parkinson patients, the gut microbiome is dysregulated and unhealthy, meaning there is an (over)growth of detrimental bacteria and a scarcity of healthy bacteria. Often, the gut microbiome is also less diversified in Parkinson’s patients.
- Small intestinal bacterial overgrowth (SIBO) is present in 25% of Parkinson’s disease patients, which is significantly higher than that in healthy adults (R).
- The amount of unhealthy gut bacteria (e.g. Enterobacteriaceae or Bacteroidetes) is associated with the severity of Parkinson’s symptoms in patients, such as gait difficulty or postural instability (R).
- The degree of absence of healthy gut bacteria (like Prevotellaceae) is also associated with severity of Parkinson’s symptoms in patients (R).
- Taking specific antibiotics (which might kill specific healthy gut bacteria) have been associated with an increased risk of Parkinson’s disease (R).
- In mice studies, antibiotic treatment (killing most bacteria in the gut, including potential unhealthy bacteria that increase Parkinson’s symptoms) improves Parkinson symptoms.
- When Parkinson-prone mice (which overexpress alpha-synuclein) receive gut bacteria from Parkinson patients, their motor impairments significantly worsen compared to when they receive gut bacteria from healthy human donors (R).
- When Parkinson-prone mice (overexpressing alpha-synuclein) receive antibiotics (which kill bacteria in their gut), their Parkinson symptoms improve (R).
- When Parkinson-prone mice (overexpressing alpha-synuclein) receive gut bacteria from Parkinson patients, their Parkinson symptoms get much worse compared to receiving gut bacteria from normal, healthy patients (R).
- Adding alpha-synuclein aggregates (clumped-together alpha-synuclein proteins) to the intestines of normal healthy mice causes behavioral problems and alpha-synuclein deposition in their brains. Adding such aggregates into the gut of Parkinson-prone mice causes degeneration of dopaminergic neurons in their brains (R).
- Fecal microbiota transplantation - in which fecal matter from healthy patients is introduced into the gut of Parkinson’s patients - could (somewhat) improve some Parkinson symptoms (R,R,R,R).
Conclusion
While the exact role of the gut microbiome in Parkinson’s disease remains to be fully elucidated, growing evidence shows that our gut health plays an important role in the disease.
Further research is needed to unravel the exact details of this gut-brain connection, this to improve the quality of life for individuals with Parkinson’s disease, and perhaps even to reduce the risk of getting the disease in the first place.
