Non-invasive microbiome-derived multi-omic biomarkers for the early-stage detection and stratification of Parkinson disease

• Applicants: Professorin Dr. Brit Mollenhauer; Professor Dr. Wolfgang Oertel
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 324158246

Do aberrations within the gastrointestinal and nasal microbiomes play a role in the initiation and progression of Parkinson disease ? Parkinson 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 alpha-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 and its progression through its most specific prodrome REM sleep behavior 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 bioinformatics analyses. The objectives of the MiBiPa project include the (i) Development of a microbiome biomarker model for Parkinson 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.

• DFG Programme: Research Grants
• International Connection: Luxembourg
• Co-Investigator: Professor Dr. Paul Wilmes