Deep nasal sinus cavity microbiota dysbiosis in Parkinson’s disease Original paper

What was studied?

This study investigated the composition and clinical relevance of the deep nasal sinus cavity microbiota in individuals with Parkinson’s disease (PD) compared to healthy controls. Recognizing that olfactory dysfunction is a common premotor symptom of PD and that the olfactory bulb may serve as a site of early neuroinflammatory activity, the researchers focused on the microbial communities residing in the deep nasal cavity, near the olfactory bulb. Using rigorous endoscopic sampling and 16S rRNA gene amplicon sequencing (both multi-amplicon and single-region V4 approaches), the study aimed to characterize the microbiota in this specific region. Comparisons were made between PD subjects, their spousal (household) controls, and randomly selected non-household healthy controls. The study also examined correlations between the abundance of specific microbial taxa and the clinical severity of PD, with the goal of identifying microbiome signatures relevant to PD pathogenesis and progression.

Who was studied?

The cohort comprised 58 participants recruited from Rush University Medical Center, including 30 individuals with established Parkinson’s disease and 28 healthy controls. Of the controls, 11 were spouses (spousal household controls, SpHC) of PD subjects (household PD, SpPD), allowing for paired comparisons within the same living environment, and 17 were random, age/gender/race-matched healthy controls (rHC) without household ties to PD subjects. All participants were evaluated to ensure the absence of underlying chronic inflammatory, infectious, or neurodegenerative conditions besides PD, and were excluded if they had recent antibiotic/probiotic use, significant comorbidities, or environmental exposures that could alter the nasal or gut microbiota. Clinical assessments included detailed neurological exams, PD severity scales (MDS-UPDRS I–IV, Hoehn & Yahr), olfactory function, and medication dosages. Deep nasal cavity samples were meticulously collected by rhinologists using endoscopic guidance to ensure high anatomical specificity.

Most important findings

The study revealed significant dysbiosis in the deep nasal sinus microbiota of PD subjects compared to controls. Key findings include:

PD subjects exhibited a unique microbial community structure in the deep nasal cavity, differing significantly from both spousal and random controls, though PD microbiomes were more similar to those of their spouses than to non-household controls, suggesting environmental influences. There was a marked increase in putative pro-inflammatory and opportunistic pathobionts in PD, particularly Moraxella catarrhalis and Ralstonia insidiosa (both Proteobacteria), while beneficial short-chain fatty acid (SCFA)-producers (e.g., Blautia wexlerae, Lachnospira pectinoschiza, Propionibacterium humerusii) and anti-inflammatory Corynebacterium species were depleted. The abundance of M. catarrhalis positively correlated with worse motor symptom scores (MDS-UPDRS IV) but negatively with Hoehn & Yahr staging, supporting a role for this taxon in PD motor phenotype expression. Staphylococcus epidermidis also correlated with motor severity, while better olfactory function was associated with higher abundance of the commensal Peptinophilus asaccharolyticus.

Although household controls shared more similar microbiomes with their PD counterparts, key differences in pathobiont abundance (notably Moraxella) remained, pointing to disease-specific rather than purely environmental drivers. The findings were robust across both multi-amplicon and single-region V4 16S rRNA sequencing approaches.

Key implications

This study provides the first evidence that the deep nasal sinus cavity microbiota is significantly altered in Parkinson’s disease, with a shift toward a pro-inflammatory microbial milieu and depletion of beneficial commensals. The proximity of these microbial shifts to the olfactory bulb, a proposed site of early neuroinflammation in PD, supports the “dual-hit hypothesis” that mucosal microbial dysbiosis may trigger or perpetuate neurodegenerative processes. The presence of specific pathobionts, such as M. catarrhalis, and their correlation with PD severity suggest potential mechanistic links warranting further investigation. Clinically, these findings highlight the potential of deep nasal microbiome profiling as a biomarker for PD and its phenotypes, and raise the possibility of targeting the nasal microbiota therapeutically. The study also underscores the value of using household controls to account for environmental factors in microbiome research. Further mechanistic and longitudinal studies are needed to determine causality and explore interventions to restore microbial balance.

Citation

Pal G, Ramirez V, Engen PA, Naqib A, Forsyth CB, Green SJ, Mahdavinia M, Batra PS, Tajudeen BA, Keshavarzian A. Deep nasal sinus cavity microbiota dysbiosis in Parkinson’s disease. npj Parkinson’s Disease. 2021;7:111. doi:10.1038/s41531-021-00254-y