Identification of proteotoxic and proteoprotective bacteria that non-specifically affect proteins associated with neurodegenerative diseases

Abstract

There are no cures for neurodegenerative protein conformational diseases (PCDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Emerging evidence suggests the gut microbiota plays a role in their pathogenesis, though the influences of specific bacteria on disease-associated proteins remain elusive. Here, we reveal the effects of 229 human bacterial isolates on the aggregation and toxicity of Aβ1-42, α-synuclein, and polyglutamine tracts in Caenorhabditis elegans expressing these culprit proteins. Our findings demonstrate that bacterial effects on host protein aggregation are consistent across different culprit proteins, suggesting that microbes affect protein stability by modulating host proteostasis rather than selectively targeting disease-associated proteins. Furthermore, we found that feeding C.elegans proteoprotective Prevotella corporis activates the heat shock response, revealing an unexpected discovery of a microbial influence on host proteostasis. Insight into how individual bacteria affect PCD proteins could open new strategies for prevention and treatment by altering the abundance of microbes.