Submitted Abstract
Parkinson’s disease (PD) research benefits from knowledge of disease-specific risk and resilience factors and elucidation of pathophysiological concepts on the emergence of neurodegeneration. Presently the propagation of a-synuclein aggregation in PD is proposed to start in the periphery, i.e. in the enteric nervous system and the olfactory bulb. Aberrations within the gastrointestinal and nasal microbiomes may play a role in the initiation of this process. Here we will focus on these two ports of entry for potential pathogenic agents in PD and hypothesize that changes in microbial community structure and function in the gastrointestinal tract as well as the nasal cavity accompany PD from its onset, progression through its most specific prodrome REM sleep behaviour disorder (RBD) to manifest PD. Our interdisciplinary team is unique as it consists of internationally recognized clinical experts in PD and RBD with active facilities enabling large-scale recruitment as well as specialists in high-resolution microbiome characterization (integrated multi-omics) and bioinformatic analyses. The objectives of the MiBiPa project include the (i) Development of a microbiome biomarker model for Parkinson’s disease based on microbiome structural and functional signatures in faeces and/or nasal lavages from an existing PD cohort, (ii) Validation of the biomarker cohort on a new cross-sectional and longitudinal cohort, (iii) Assessment of the applicability of the biomarker for early diagnosis of high-risk cohorts (i.e. RBD), and (iv) Contribute to the understanding of the disease development by characterizing PD-specific microbiota. This is of particular relevance in relation to the development of future disease-modifying neuroprotective therapies that would require intervention at the earliest stages of disease but also to identify preventive strategies for the conversion to, i.e. manifest PD. Therefore, MiBiPa aims to have a durable and significant impact on better identification, prevention, treatment and management of PD.