In a recent Npj Biofilms and Microbiomes journal study, researchers conducted an integrative metaproteogenomic evaluation to characterize saliva samples collected from patients with Parkinson’s disease (PD) experiencing cognitive impairments.

Study: Metaproteogenomic evaluation of saliva samples from Parkinson’s disease patients with cognitive impairment. Image Credit: Ground Picture / Shutterstock.com

Background

PD is a neurodegenerative disorder that’s globally prevalent. In the longer term, the incidence of PD is anticipated to substantially increase attributable to the aging population.

Mechanistically, alpha-synuclein (α-syn) aggregates accumulate within the neurons of PD patients, causing significant disruption in each motor and non-motor functions. Cognitive impairment (CI) is one of the crucial common non-motor symptoms of PD.

PD symptoms progressively worsen with time, with a shift from mild cognitive impairment (MCI) to full-scale dementia (PDD). Several studies have indicated that PD patients are at a greater risk of dementia, as almost half of PD patients develop dementia inside 10 years of diagnosis, and just about all patients develop dementia inside 20 years from diagnosis.

It is incredibly difficult for PD patients to live independent lives, thus necessitating the necessity for care from families and nursing homes. The families of PD patients suffer a big economic burden; due to this fact, it might be highly useful to discover PD patients at an increased risk of developing cognitive decline to implement preventive or delaying measures.

Saliva incorporates host cells, biomolecules, and microbiota, thus reflecting its potential source of biomarkers for a lot of chronic diseases. Previous studies have revealed that α-syn may be detected in cerebrospinal fluid (CSF) and saliva. In PD patients, α-syn results in poor secretion of dysphagia and saliva. 

Drooling is a standard oral motor disorder of PD that has been linked to CI in these patients. Oral microbiota dysbiosis has also been observed in PD patients and is related to drooling, oral pH, and dysphagia.

In regards to the study

The present study hypothesized that dynamic shifts in salivary biomolecules and microbiota occur with CI progression in PD. Moreover, saliva samples may very well be used to predict CI stages in PD.

Metaproteogenomic evaluation was used to check this hypothesis. Here, 16 S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing was integrated with metaproteomics data developed from saliva samples.

A complete of 115 candidates were recruited on this study to find out whether shifts in saliva composition can assist discover different CI stages in PD patients. All study participants were between 50 and 75 years of age. All control group participants underwent neuropsychological testing, and their cognitive capability was assessed.

Study findings

The composition of the saliva of PD patients was determined based on 16 S rRNA gene amplicon sequencing and metaproteomics profiling and was compared with controls. Integrative metaproteogenomics enabled the determination of distinct saliva composition signatures related to CI stages of PD.

An integrative evaluation of saliva metaproteomics and metagenomics highlighted dynamic shifts within the salivary microbiome and changes in protein translation machinery and defense mechanisms related to the CI progression in PD.

According to previous studies, the metaproteomic and metagenomic profiles indicated the abundance of Prevotella, Streptococcus, Fusobacterium, Veillonella, and Neisseria within the PD cohort as in comparison with controls. Compared to metaproteomics profiling, many more bacterial genera, phyla, and families were identified through the amplicon sequencing approach. This may very well be attributed to only a subset of bacterial genera which have been used to develop a custom-based standard protein database to discover proteins.

The study groups had no significant difference in alpha diversity in amplicon-based microbiota. In contrast, considerable changes within the beta diversity of saliva samples were observed between groups that significantly distinguished CI stages.

Thus, the salivary bacterial community changes and re-rearranges with the progression of CI. According to a previous study, the present study reports a decrease in the Neisseria genus with the progression of CI in PD patients.

Metaproteome profiles indicated a differential composition that contributed to functional changes linked with CI. Furthermore, functions related to biogenesis, ribosomal structure, cytoskeleton and translation, energy production and conversion, and defense mechanisms were amongst probably the most significantly modified functions between the PD and control cohorts.

The decrease in Neisseria has attracted significant attention because this taxon is related to the prevention of oral diseases through the conversion of low-pH products into weak acids. As well as, the presence of a high level of Lactobacillaceae members within the oral cavity of PD patients has been linked to many adversarial effects attributable to a reduced secretion of neuroprotective hormones like ghrelin.

The study findings indicate a continuous shift in saliva microbiota composition across the CI spectrum in PD. A big lowering of pyruvate phosphate dikinase (PPDK) enzyme, which plays a very important role in gluconeogenesis and lactic acid production, also emerged as a possible biomarker for CI during PD.

Bactericidal permeability-increasing (BPI) proteins, that are related to host defenses against bacterial pathogens, were also identified as microbial translocation markers. A decrease in salivary BPI abundance indicates a possible BPI imbalance in PD patients that deteriorates with CI progression.

Conclusions

The present study determined that changes in salivary microbiota and biomolecules may be used to detect the CI stages in PD patients. Although the microbial taxa identified on this study are robust, more studies are needed to substantiate the saliva proteins linked to CI in PD.