Alterations in the microbiota have been observed in many human diseases including diseases of neurodegeneration. However, specific microbiome factors that either promote or protect against neurodegeneration are largely unknown. We are examining the effects of human microbiota in tauopathies, a class of age-associated neurodegenerative diseases that are characterized by the accumulation and aggregation of the microtubule-associated protein Tau. Mutations in the gene encoding Tau (MAPT) result in Frontotemporal Lobal Degenerations (FTLDs). Using a Caenorhabditis elegans model of this disease, we examined the impact of exposure to specific bacteria present in the human microbiome on neurodegeneration. We identified strains of bacteria that are neuroprotective in this model of tauopathy, and one that promotes neurodegeneration. Rothia species that suppress neurodegeneration also influence fat metabolism in C. elegans. We determined that the ability of Rothia species to promote neuroprotection in the PLM neurons requires the fatty acid desaturate
fat-3.
fat-3 mutants lack D6 fatty acids and are depleted in C20 fatty acids. We are currently investigating the mechanism of
fat-3 dependent neuroprotection and investigating how Rothia exposure modifies lipid metabolism.