induces mitochondrial calcium overload and α -synuclein aggregation in an enteroendocrine cell line.

The gut microbiota influence neurodevelopment, modulate behavior, and contribute to neurodegenerative disorders. Several studies have consistently reported a greater abundance of in Parkinson disease (PD) fecal samples. Therefore, we investigated whether -conditioned medium (CM) could initiate α-synuclein (αSyn) misfolding in enteroendocrine cells (EEC) - a component of the gut epithelium featuring neuron-like properties. We found that . CM composition is influenced by the ability of the strain to degrade mucin. Our experiments showed that the protein-enriched fraction of mucin-free CM induces RyR-mediated Ca release and increased mitochondrial Ca uptake leading to ROS generation and αSyn aggregation. Oral administration of cultivated in the absence of mucin to mice led to αSyn aggregation in cholecystokinin (CCK)-positive EECs but no motor deficits were observed. Noteworthy, buffering mitochondrial Ca reverted the damaging effects observed. These molecular insights offer evidence that bacterial proteins can induce αSyn aggregation in EECs.