Imbalance of gut microbiota may lead to Parkinson’s disease
“Research has shown that Parkinson’s is often diagnosed late, and it can originate much earlier in the enteric nervous system [which controls gastrointestinal motility]before reaching the brain via autonomic fibers,” Matheus de Castro Fonseca, the study’s principal investigator, told Agência FAPESP. Fonseca is currently undertaking postdoctoral research on the subject at the California Institute of Technology. (Caltech) in the United States.
Recent publications have consistently reported the existence of intestinal dysbiosis in sporadic Parkinson’s patients, as the non-heritable form of the disease is known, and have shown that Akkermansia muciniphila has more abnormalities in stool samples of these patients compared with controls.
“Specific cells in the intestinal epithelium, known as enterocytes, have recently been found to have many neuron-like properties, including expression of the alpha-synuclein protein. [αSyn]. Parkinson’s and other neurodegenerative diseases are associated with the abnormal accumulation and aggregation of this protein, Fonseca said. Endocrine cells form a neural circuit between the gastrointestinal tract and the enteric nervous system. Therefore, they may be a key factor in the development of Parkinson’s disease in the gut. ”
With this knowledge, the CNPEM team set out to see if substances secreted by A. muciniphila could trigger α-Syn incorporation in endothelial cells and whether αSyn was assembled in the cells. Can these cells then migrate to peripheral nerve endings in the enteric nervous system?
“We cultured the proteins secreted by these bacteria in the absence of intestinal mucus and found that they lead to intracellular calcium overload in endocytic cells, putting stress on their mitochondria. [energy-producing organelles]activates synthesis and release of reactive oxygen species [an excess of which damages intracellular structures]and induce αSyn aggregation,” says Fonseca. Furthermore, when we cultured enteroendocrine cells and neurons together, we found that synthetic αSyns could be transferred from one to the other. ”
This discovery is important because it shows that dysbacteriosis can promote the growth of bacteria that may contribute to αSyn incorporation in the gut and subsequent protein migration to the central nervous system, configure a possible mechanism for the development of sporadic Parkinson’s disease.
“The chain reaction can start in the gut and move up to the brain,” says Fonseca. “People predisposed to sporadic Parkinson’s disease often experience recurrent constipation years before they manifest the disease. In our study with animal models, we found a direct correlation between the disorder.” gut biology and Parkinson’s disease.”
New prevention strategies
Research into the human microbiome is progressing rapidly, as is scientists’ understanding of the link between imbalances in the gut microbiome and degenerative disorders. neurological conditions, from Parkinson’s and Alzheimer’s to autism. Dietary changes aimed at restoring balance to the gut, as well as non-invasive microbiota transplantation using capsules, may be important strategies to prevent these diseases. .
“Neurodegenerative diseases are incurable right now, so prevention is fundamental,” says Fonseca. “Research used to focus on the brain, and very little progress has been made in this direction for decades. Instead, we are now focusing on the gut. The latest discoveries look very promising. It’s much easier to regulate the gut microbiome than it is to deal with well-established disorders in the central nervous system.”
Research is funded by FAPESP through the Continuing Research Grants and master’s scholarships. It also benefits from the use of facilities and equipment at the National Institute of Photonics Applied to Cell Biology, chaired by the University of Campinas (UNICAMP) and funded by FAPESP and the Development Council. National Science and Technology (CNPq).