The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder Original paper

What was studied?

This original research article examined the nasal and gut microbiome in Parkinson’s disease to determine whether microbial shifts previously observed in Parkinson’s disease (PD) also appear in individuals with idiopathic REM sleep behavior disorder (iRBD), a prodromal condition strongly associated with eventual PD development. The investigators analyzed microbial DNA from flash-frozen nasal wash and stool samples to characterize bacterial, archaeal, and microeukaryotic communities and assess how these communities differ between PD, iRBD, and healthy controls. Using 16S and 18S rRNA gene amplicon sequencing, supplemented by whole-metagenome sequencing for select samples, the study aimed to link specific microbial signatures with motor and nonmotor symptoms, including depression, constipation, and sleep abnormalities.

Who was studied?

The cohort included 76 patients with clinically verified PD, 21 individuals with polysomnography-confirmed iRBD, and 78 healthy controls matched for age and sex. All participants were part of the rigorously phenotyped DeNoPa cohort, with extensive clinical characterization including motor severity (MDS-UPDRS), autonomic dysfunction, depression scales, cognitive assessments, and sleepiness metrics. Stool and nasal samples were collected under controlled clinical conditions and immediately flash-frozen to minimize technical variability. Medication exposures, comorbidities, and demographic variables were included as covariates to control for their influence on microbiome composition.

Most important findings

The nasal microbiome showed high inter-individual variability and minimal disease-related differences after controlling for sex, suggesting limited biomarker potential. In contrast, the gut microbiome displayed clear distinctions between groups. PD patients exhibited 48 differentially abundant gut microbial OTUs compared to healthy controls, while iRBD subjects exhibited 41 such OTUs. More than 75% of PD- and iRBD-associated taxa showed shifts in the same direction relative to controls, suggesting early microbial alterations before motor symptom onset. Notable PD-associated increases included Akkermansia (Verrucomicrobia), while several Anaerotruncus, Clostridium XIVa/XIVb, and Bacteroides species differed significantly across groups. Specific gut taxa correlated with nonmotor symptoms such as depression and anxiety. Whole-metagenome sequencing identified uncharacterized taxa—including a Melainabacterium and an alpha-proteobacterium—depleted in PD and iRBD; one genome contained a synuclein-like domain, highlighting potential mechanistic relevance. Nasal–gut microbial overlap appeared limited, supporting distinct ecological roles.

Key implications

These findings strengthen evidence that gut microbiome alterations characterize both PD and its prodrome, iRBD, long before motor symptom onset. The enrichment of Akkermansia and consistent shifts in Anaerotruncus and Bacteroides spp. align with growing hypotheses linking gut barrier dysfunction, inflammation, and microbial metabolites to α-synuclein aggregation. Identification of novel, previously unsequenced bacterial genomes underscores the value of metagenomics for expanding microbiome signature databases. The minimal nasal microbiome signal suggests that gut signatures may provide stronger diagnostic or prognostic biomarker value, especially for identifying at-risk individuals during the prodromal phase.

Citation

Heintz-Buschart A, Pandey U, Wicke T, et al. The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder. Movement Disorders. 2018;33(1):88-98