[Investigation of the Relationship Between Akkermansia Genomic Diversity in Gut Microbiota and Parkinson's Disease Dementia]. / Parkinson Hastaligi Demansi ile Bagirsak Mikrobiyotasindaki Akkermansia Genomik Çesitliligi Arasindaki Iliskinin Incelenmesi.

Although it is known that the relative abundance of Akkermansia, a bacterial genus commonly associated with health, increases in the gut microbiota of Parkinson's disease (PD) patients, the exact reason for this increase remains unclear. This study was aimed to identify potential changes in Akkermansia within the gut microbiota of PD patients in Türkiye. For this purpose, shotgun metagenomics and a novel Akkermansia genus-specific amplicon sequencing technique was used to investigate the presence of specific Akkermansia strains associated with cognitive impairment (CI) stages in PD and to examine potential genes within these strains. In this context, four gut microbiota samples from Türkiye -three PD with dementia (PDD) and one healthy control without CI (HC)- were analyzed by shotgun metagenomics and metagenome-assembled genomes assigned to Akkermansia genus were reconstructed. Then, a custom database was created by combining these genomes with the Akkermansia genomes in public databases and next generation sequencing (NGS) compatible primers specific to the genus Akkermansia were designed using this database. After optimization of amplification and library preparation steps for genus-specific next generation sequencing, gut microbiota samples from 64 PD patients [32 PDD and 32 PD with mild CI (PD-MCI)] and 26 HCs were analyzed by genus-specific amplicon sequencing. The results revealed the presence of seven strains assigned to Akkermansia muciniphila in gut microbiota samples, two of which showed significant distribution differences (p< 0.05) between demented (PDD) and non-demented groups (PD-MCI, HC). When gene contents of the detected Akkermansia genomes were examined through comparative genomic analysis, the presence of 12 genes only in Akkermansia genomes specific to non-demented groups were predicted. The annotations of these genes showed that they were not reported before with unknown functions. In this study, for the first time, gut microbiota samples from PD patients in Türkiye were analyzed using shotgun metagenomics, a novel genus-specific amplicon sequencing method was developed specifically for the analysis of Akkermansia genus, and then Akkermansia strains and genes potentially associated with CI stages in PD were identified using this method. The results underscore that investigating the species or strain level differences could help better understanding of the changes associated with PD in the human gut microbiota.

Axillary Microbiota Is Associated with Cognitive Impairment in Parkinson's Disease Patients.

Cognitive impairment (CI) is among the most common non-motor symptoms of Parkinson's disease (PD), with a substantially negative impact on patient management and outcome. The development and progression of CI exhibits high interindividual variability, which requires better diagnostic and monitoring strategies. PD patients often display sweating disorders resulting from autonomic dysfunction, which has been associated with CI. Because the axillary microbiota is known to change with humidity level and sweat composition, we hypothesized that the axillary microbiota of PD patients shifts in association with CI progression, and thus can be used as a proxy for classification of CI stages in PD. We compared the axillary microbiota compositions of 103 PD patients (55 PD patients with dementia [PDD] and 48 PD patients with mild cognitive impairment [PD-MCI]) and 26 cognitively normal healthy controls (HC). We found that axillary microbiota profiles differentiate HC, PD-MCI, and PDD groups based on differential ranking analysis, and detected an increasing trend in the log ratio of Corynebacterium to Anaerococcus in progression from HC to PDD. In addition, phylogenetic factorization revealed that the depletion of the Anaerococcus, Peptoniphilus, and W5053 genera is associated with PD-MCI and PDD. Moreover, functional predictions suggested significant increases in myo-inositol degradation, ergothioneine biosynthesis, propionate biosynthesis, menaquinone biosynthesis, and the proportion of aerobic bacteria and biofilm formation capacity, in parallel to increasing CI. Our results suggest that alterations in axillary microbiota are associated with CI in PD. Thus, axillary microbiota has the potential to be exploited as a noninvasive tool in the development of novel strategies. IMPORTANCE Parkinson's disease (PD) is the second most common neurodegenerative disease. Cognitive impairment (CI) in PD has significant negative impacts on life quality of patients. The emergence and progression of cognitive impairment shows high variability among PD patients, and thus requires better diagnostic and monitoring strategies. Recent findings indicate a close link between autonomic dysfunction and cognitive impairment. Since thermoregulatory dysfunction and skin changes are among the main manifestations of autonomic dysfunction in PD, we hypothesized that alterations in the axillary microbiota may be useful for tracking cognitive impairment stages in PD. To our knowledge, this the first study characterizing the axillary microbiota of PD patients and exploring its association with cognitive impairment stages in PD. Future studies should include larger cohorts and multicenter studies to validate our results and investigate potential biological mechanisms.