Amyloids are a class of protein with unique self-aggregation properties, and 
their aberrant accumulation can lead to cellular dysfunctions associated with 
neurodegenerative diseases. While genetic and environmental factors can 
influence amyloid formation, molecular triggers and/or facilitators are not well 
defined. Growing evidence suggests that non-identical amyloid proteins may 
accelerate reciprocal amyloid aggregation in a prion-like fashion. While humans 
encode ~30 amyloidogenic proteins, the gut microbiome also produces functional 
amyloids. For example, curli are cell surface amyloid proteins abundantly 
expressed by certain gut bacteria. In mice overexpressing the human amyloid 
α-synuclein (αSyn), we reveal that colonization with curli-producing Escherichia 
coli promotes αSyn pathology in the gut and the brain. Curli expression is 
required for E. coli to exacerbate αSyn-induced behavioral deficits, including 
intestinal and motor impairments. Purified curli subunits accelerate αSyn 
aggregation in biochemical assays, while oral treatment of mice with a 
gut-restricted amyloid inhibitor prevents curli-mediated acceleration of 
pathology and behavioral abnormalities. We propose that exposure to microbial 
amyloids in the gastrointestinal tract can accelerate αSyn aggregation and 
disease in the gut and the brain.