Impact of Microbiota on Neurodegeneration in Tauopathies using Caenorhabditis elegans as a Model Organism

Abstract

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 examined the effects of human microbiota in tauopathies, a class of age-associated neurodegenerative diseases that are characterized by the accumulation of tau protein inclusions. Using a Caenorhabditis elegans model expressing an aggregate prone human tau protein, we examined the influence of specific bacteria present in the human respiratory tract on neurodegeneration. We identified a bacterial species, Rothia aeria, that is neuroprotective in a C. elegans model of tauopathy. We determined that the R. aeria induced neuroprotection observed in PLM neurons is fat-3 dependent. fat-3 encodes the protein Delta (6)-fatty-acid desaturase. We also showed that a lipid(s) produced by R. aeria decreases neurodegeneration in C. elegans. Further investigation is needed to identify the lipid and the underlying mechanism.