Objective: We aimed to identify the nasal, oral, and gut microbiota dysbiosis associated with the presence and clinical manifestations of Parkinson’s disease (PD) using 16s RNA gene sequencing and shotgun sequencing. In addition, we investigated optimal methods for microbiota analysis to be used as diagnostic biomarker.

Background: Gut microbiota dysbiosis have become a research focus worldwide, and several studies suggested gut microbiota as potential diagnostic biomarker for PD. According to Braak’s hypothesis, pathologic aggregation of α-synuclein begins in the olfactory bulb and gut before spreading through the central nervous system. Therefore, microbiota in the nasal and oral region as well as the gut might affect the development and clinical manifestations of PD. Currently, 16s RNA sequencing has been widely used, but shotgun sequencing has advantages over 16s RNA sequencing in the detection of high resolution community as species level.

Method: This case-control study investigated gut microbial gene in the nasal, oral, and faeces from 91 patients with PD and 85 their healthy spouses using 16s ribosomal RNA and shotgun metagenomic sequencing.

Results: Alpha-diversity of gut microbiota indicated by the Shannon index was higher in patients with PD than that in controls (p<0.001), while alpha-diversity of oral and nasal microbiota was not significantly different between 2 groups. Beta diversity, measured as Bray-Curtis dissimilarity, of gut, nasal and oral microbiota were significantly different between 2 groups (p-value range 0.001─0.004). In the gut, Bifidobacterium was higher, and Faecalibacterium was lower in patients with PD than in controls, both of which are correlated well with disease severity. While Prevotella was lower in patients with PD, it did not correlate with disease severity. Age at disease onset and olfactory dysfunction were correlated with Enterococcus, and Sporobacter in the gut. Oral Desulfobulbus was correlated with dysphagia. Gut microbiota using 16s RNA analysis distinguished PD better than nasal and oral microbiota (AUC 0.76 vs 0.69 vs 0.68). Shotgun analysis of gut microbiota distinguished PD better than 16s RNA analysis of gut microbiota (AUC 0.89 vs 0.76).

Conclusion: This study identified gut, nasal and oral dysbiosis of PD in association with clinical manifestations. Also, we found that shotgun analysis of gut microbiota showed best diagnostic accuracy for PD than 16s RNA analysis of nasal, oral, or gut microbiota.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gut-nasal-and-oral-dysbiosis-in-parkinsons-disease/