Despite being a disease in the brain, new research suggests an unhealthy gut could lead to the development of Parkinson’s disease. Two new studies from Brazil showed a mechanism by which Parkinson’s can occur from an imbalance between ‘good’ and ‘bad’ gut microbes.
“Research has shown that Parkinson’s is often diagnosed late and that it may originate much earlier in the enteric nervous system [which controls gastrointestinal motility], before advancing to the brain via autonomic fibers,” says Matheus de Castro Fonseca, principal investigator for the study and postdoctoral researcher at the California Institute of Technology in a media release.
Previous studies have observed a gut imbalance in patients with sporadic Parkinson’s, a non-genetic version of the disease. They also showed that these patients had high amounts of the bacteria Akkermansia muciniphila in their feces compared to people without Parkinson’s disease.
“Specific cells in the gut epithelium, called enteroendocrine cells, have recently been found to have many neuron-like properties, including expression of the protein alpha-synuclein [αSyn]. Parkinson’s and other neurodegenerative diseases are known to be associated with abnormal accumulation and aggregation of this protein,” Fonseca explains. “Because they’re in direct contact with the gut lumen – the space inside the intestines – and connected by synapses to the enteric neurons, enteroendocrine cells form a neural circuit between the gastrointestinal tracts and the enteric nervous system. As such, they may be a key factor in the emergence of Parkinson’s in the gut.”
The group looked to see if substances that release A. muciniphila could trigger α-Syn aggregation in enteroendocrine cells. If so, they speculate that it is possible for αSyn to then aggregate in these cells which migrate to peripheral nerve terminals in the enteric nervous system.
They isolated proteins secreted from A. muciniphila and found they led to intracellular calcium overload in enteroendocrine cells. The excess calcium stresses the cell’s mitochondria which then causes intracellular damage and α-Syn aggregation. When enteroendocrine cells and neurons were together, they found the aggregated α-Syn could transfer to neurons.
The findings suggest a gut imbalance could promote bacteria that trigger α-Syn aggregation n the gut. The protein could then travel to the brain and promote the development of sporadic Parkinson’s.
“The cascade of reactions can start in the gut and move up into the brain,” Fonseca says. “People predisposed to sporadic Parkinson’s usually suffer from recurring constipation many years before they manifest the disease. In our study with animal models, we found a direct correlation between gut dysbiosis and Parkinson’s.”
Right now, there is no cure for Parkinson’s. But making changes to your diet by including healthy and gut-friendly foods may be a way to prevent these diseases.
“Neurodegenerative diseases are incurable right now, so prevention is fundamental,” Fonseca explains. “Research used to focus on the brain, and little progress was made in this direction for decades. We’re now focusing on the gut instead. The latest discoveries seem highly promising. It’s much easier to modulate the gut microbiota than to deal with a well-established disorder in the central nervous system.”