15 November 2022

Microflora of parkinsonics

The microbiome of people with Parkinson's disease contributes to pathological processes

Yulia Panchenko, PCR.news

The microbiota performs many important functions in the body — it helps with the metabolism of food, produces important metabolites such as vitamins, maintains the integrity of the intestinal barrier, suppresses pathogens, regulates the development and training of the immune system. Dysbiosis makes the body more susceptible to diseases. Dysbiosis is found in many conditions, such as diabetes, Parkinson's disease and autism spectrum disorders.

Parkinson's disease is a multisystem and etiologically heterogeneous disease. There are several genetic and environmental factors, but in most cases the cause cannot be determined. Patients often suffer from constipation even before symptoms appear. The pathology of alpha-synuclein is detected in the intestine in the early stages of the disease. There is a hypothesis that the disease begins in the intestine and spreads to the brain, but this has not been proven by Pak. Scientists from the USA and the UK conducted a large-scale study of the metagenome of patients with Parkinson's disease. They identified dysbiosis in such patients, identified the species responsible for dysbiosis, and also make assumptions about genes and signaling pathways that play a role in the development of the disease.

The study included 490 patients with Parkinson's disease and 234 controls. The controls were often performed by the spouses of patients. Stool samples were taken from all participants, DNA was extracted from them and sequenced using the shotgun method.

Patients had more gastrointestinal problems, such as constipation, than controls. These factors and others, such as alcohol intake, medications, probiotics, diet, were taken into account in the analysis.

The authors studied certain types of microorganisms associated with Parkinson's disease. In total, they identified 2,270 species, including bacteria, archaea and eukaryotes, and 719 passed quality control. Of these, 257 species were found in 5% of the participants or more. The analysis showed that 84 out of 257 species were associated with Parkinson's disease: 55 species were present in greater numbers, 29 — in less. Thus, the number of Bifidobacterium dentium bacteria in patients was seven times higher, Actinomyces oris — 6.5 times, Streptococcus mutans - six times. On the other hand, Roseburia intestinalis was 7.5 times smaller, and Blautia wexlerae was five times smaller. Additional analysis confirmed the association of 32 species with pathology, another 30 species were associated with pathology and another variable, such as alcohol intake and laxatives.

The species that most often appear together were identified, as well as species that "avoid" each other. Opportunistic pathogens Escherichia coli, Klebsiella pneumoniae and Klebsiella quasipneumoniae are more common in patients with Parkinson's disease.

The new work confirmed the data obtained earlier by sequencing 16S rRNA, and also helped refine the results to the species. Thus, it was confirmed that Blautia, Faecalibacterium, Fusicatenibacter, Roseburia and Ruminococcus are present in smaller quantities in patients, and Bifidobacterium, Hungatella, Lactobacillus, Methanobrevibacter and Porphyromonas are present in large quantities. Some sources claimed that Prevotella is more common in patients, some less common. The authors have shown that the content Prevotella copri is downgraded, and pathogenic species Prevotella — elevated in patients with Parkinson's disease.

The researchers identified 8528 gene families and 511 metabolic pathways. According to their estimates, one-third to two-thirds of the metabolic pathways were deregulated in patients. The microbiome of patients with Parkinson's disease contributes to pathogenesis — they have more opportunistic pathogens, more immunogenic components and toxins are produced, the regulation of neuroactivation signaling is disrupted, molecules that contribute to the formation of amyloids that induce alpha-synuclein pathology prevail. At the same time, they have fewer anti-inflammatory and neuroprotective molecules.

The authors obtained a large amount of data on metagenomic sequencing by the shotgun method at the level of individual individuals and made them open. They showed that dysbiosis is characteristic of patients with Parkinson's disease, and their microbiome contributes to the development of pathologies and hinders recovery.

Article by Wallen et al. The metagenomics of Parkinson's disease implies the gut microbiome in multiple disease mechanisms is published in the journal Nature Communications.

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