“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,” Matheus de Castro Fonseca, principal investigator for the research, advised Agência FAPESP. Fonseca is at present doing postdoctoral analysis on the topic on the California Institute of Technology (Caltech) within the United States.
Recent publications have constantly reported the existence of intestine dysbiosis in sufferers with sporadic Parkinson’s, because the non-inherited type of the illness is thought, and proven that the micro organism Akkermansia muciniphila is abnormally considerable in fecal samples from these sufferers in comparison with controls.
“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 stated. “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.”
With this data in thoughts, the CNPEM group got down to see if substances secreted by A. muciniphila would possibly set off α-Syn aggregation in enteroendocrine cells and whether or not the αSyn aggregated in these cells may then migrate to peripheral nerve terminals within the enteric nervous system.
“We cultured proteins secreted by these bacteria in the absence of intestinal mucus and found them to lead to intracellular calcium overload in enteroendocrine cells, stressing their mitochondria [energy-producing organelles]triggering synthesis and release of reactive oxygen species [an excess of which damages intracellular structures]and causing αSyn aggregation,” Fonseca stated. “Moreover, when we cultured enteroendocrine cells and neurons together, we found that aggregated αSyn can be transferred from one to the other.”
The discovery is essential as a result of it exhibits that dysbiosis can enhance the expansion of micro organism that would contribute to αSyn aggregation within the intestine, and that the protein might then migrate to the central nervous system, configuring a doable mechanism for the event of sporadic Parkinson’s.
“The cascade of reactions can start in the gut and move up into the brain,” Fonseca stated. “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.”
New prevention methods
Research on the microbiomes current within the human organism is advancing quickly, as is scientists’ understanding of the hyperlinks between an imbalance within the intestine microbiota and neurodegenerative problems, from Parkinson’s and Alzheimer’s to autism. Dietary adjustments geared toward restoring a stability to the intestine, in addition to non-invasive transplantation of microbiota utilizing capsules, could be vital methods to forestall these illnesses.
“Neurodegenerative diseases are incurable right now, so prevention is fundamental,” Fonseca stated. “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.”
The research was funded by FAPESP through a Regular Research Grant and a grasp’s scholarship. It additionally benefited from use of services and gear on the National Institute of Photonics Applied to Cellular Biology, hosted by the University of Campinas (UNICAMP) and funded by FAPESP and the National Council for Scientific and Technological Development (CNPq).