They discover the presence of amyloids associated with Parkinson’s disease in the intestinal microbiota

It is estimated that in the world there are more than 7 million people with Parkinson’s disease, and that in Spain alone the figure rises to about 160,000 affected, according to the Spanish Parkinson’s Federation.

Age-related neurodegenerative diseases involving amyloid aggregation remain one of the greatest challenges in modern medicine. It has long been known that alterations of the gastrointestinal microbiome play an active role in the etiology of neurological disorders.

Now, a team led by Ariadna Fernández-Calvet, from the Institute of Agrobiotechnology (IDAB), a joint center of the Government of Navarra and the Higher Council for Scientific Research (CSIC), in Spain, has discovered the presence of bacterial amyloids associated with the disease Parkinson’s disease in the intestinal microbiota (the microorganisms that live in our digestive system). The finding could provide tools to make an early diagnosis of the pathology.

The microbiota of the intestinal tract forms the most abundant biofilm in the human body and has a considerable impact on a person’s health and disease. This has made it possible to demonstrate that the bacteria that live in the human intestine produce biofilm-associated proteins (BAP) that assemble to form amyloids. Bacterial amyloids, which have a fibrillar structure similar to human amyloids, accumulate in the intestine and could be involved in the development of diseases. Using human fecal samples, the research team has been able to detect the presence of bacterial amyloids, which has made it possible to evaluate their potential neurodegenerative activity.

By reanalyzing metagenomic data from patients with Parkinson’s disease and neurologically healthy controls, researchers have shown that the abundance of genes encoding BAP proteins in the gut microbiome correlates with Parkinson’s disease. These genes are located in the accessory genome of the microbiota, suggesting that only certain bacterial strains will have the potential to produce amyloid. This underlines the importance of analyzing the genetic content of the microbiota rather than focusing only on the presence of certain bacterial species.

Through different trials, including the culture of dopaminergic neurons, Caenorhabditis elegans and mouse models, the scientific team has shown that bacterial amyloids interact with alpha-synuclein and accelerate its accumulation. An abnormal buildup of the protein alpha-synuclein is associated with Parkinson’s disease. Exposure to bacterial amyloids in the brain of mice significantly increases the half-life of alpha-synuclein. The decrease in alpha-synuclein turnover is associated with a decrease in LAMP-2A levels, suggesting that chaperone-mediated autophagy activity is compromised by BAP amyloids, a situation described and associated with Alzheimer’s disease. Parkinson.

Microscopy image of neurons treated with bacterial amyloids in which alpha-synuclein aggregates are detected. (Photo: IdAB / CSIC)

“This research fills a gap in knowledge, not only of the pathological aspects of Parkinson’s disease, but also of its initial stages at the intestinal level. Our results may have important implications for developing tools that allow earlier diagnosis and more effective therapies aimed at the initial stages of this pathology,” says Jaione Valle, scientist at the Institute of Agrobiotechnology and co-author of the study.

Research staff from the Biomedical Research Center of La Rioja, the University of Navarra and its CIMA center, the Autonomous University of Barcelona, ​​HM Hospitales, NASERTIC and Navarrabiomed have also collaborated in the research.

The study is titled “Gut microbiota produces biofilm-associated amyloids with potential for neurodegeneration.” And it has been published in the academic journal Nature Communications. (Source: IDAB / CSIC)