Lewy Body Disease (LBD) is the second most common neurodegenerative disorder after Alzheimer's disease. Pathologically, LBD is characterized by immunopositive α-synuclein aggregations in the form of Lewy bodies. Given this context, improving our understanding of what triggers α-synuclein aggregation, and promotes disease progression, is crucial. Gastrointestinal concerns (e.g. constipation) are an independent early clinical pre-motor/cognitive dysfunction feature of LBD, which places the gut and thus microbiome at the center of Lewy body research.
Assistant Professor Levi Teigen (Food Science and Nutrition) and Assistant Professor Christopher Staley (Surgery; MSI PI) are working on a project called “Determination of Functional Drivers of Lewy Body Disease among the Intestinal Microbiota,” that extends this area of research. In collaboration with neurology colleagues at Mayo Clinic, they leveraged healthy controls from their Microbiota Therapeutics stool donor program against patients with LBD and cohabitant controls to identify a gut dysbiosis characterized by decreased short-chain fatty acid producing taxa in patients with LBD. Their central hypothesis is that dysbiosis underlying LBD results in microbial ecosystem services favoring the accumulation and propagation of abnormal α-synuclein. They will perform whole genome shotgun sequencing of DNA previously analyzed by 16S rRNA amplicon sequencing to 1) evaluate differences in functional pathways between LBD patients, cohabitant controls, and healthy controls; and 2) develop a Bayesian model of directional interactions to build a model of disease development (i.e. predictive index). This project promises novel insights into microbiome-targeted therapy for early-stage LBD and could mark a major advancement in the treatment of this devastating neurodegenerative disorder.
This project recently received a DSI Seed Grant. DSI Seed Grant funds are intended to promote, catalyze, accelerate, and advance U of M-based data science research so that U of M faculty and staff are well prepared to compete for longer term external funding opportunities. Priority is given to projects that will enable or bridge applications to larger funding opportunities and/or create new cross-disciplinary or cross-system collaborations, and to those that align with at least one of the areas of the MnDRIVE initiative. Projects must align with one of the current DSI focus areas, Foundational Data Sciences or Digital Health and Personalized Health Care Delivery. This project falls under the Brain Conditions research area of the MnDRIVE initiative and the Foundational Data Sciences focus area.
