1 Scientific RepoRts | 6:34477 | DOI: 10.1038/srep34477 www.nature.com/scientificreports exposure to the Functional Bacterial Amyloid protein Curli enhances Alpha- synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans shu G. Chen 1 , Vilius stribinskis 2 , Madhavi J. Rane 3 , Donald R. Demuth 4 , evelyne Gozal 5 , Andrew M. Roberts 6 , Rekha Jagadapillai 5 , Ruolan Liu 7 , Kyonghwan Choe 1 , Bhooma shivakumar 1 , Francheska son 1 , shunying Jin 3 , Richard Kerber 8 , Anthony Adame 9 , eliezer Masliah 9 & Robert p. Friedland 7 Misfolded alpha-synuclein (As) and other neurodegenerative disorder proteins display prion-like transmission of protein aggregation. Factors responsible for the initiation of As aggregation are unknown. to evaluate the role of amyloid proteins made by the microbiota we exposed aged rats and transgenic C. elegans to E. coli producing the extracellular bacterial amyloid protein curli. Rats exposed to curli-producing bacteria displayed increased neuronal As deposition in both gut and brain and enhanced microgliosis and astrogliosis compared to rats exposed to either mutant bacteria unable to synthesize curli, or to vehicle alone. Animals exposed to curli producing bacteria also had more expression of TLR2, IL-6 and TNF in the brain than the other two groups. There were no diferences among the rat groups in survival, body weight, infammation in the mouth, retina, kidneys or gut epithelia, and circulating cytokine levels. As-expressing C. elegans fed on curli-producing bacteria also had enhanced As aggregation. these results suggest that bacterial amyloid functions as a trigger to initiate As aggregation through cross-seeding and also primes responses of the innate immune system. Te neurodegenerative disorders Parkinson’s disease (PD), Alzheimer’s disease, fronto-temporal lobar degen- eration, amyotrophic lateral sclerosis and related disorders all involve the neuronal accumulation of pathogenic aggregated amyloid proteins with prion-like features 1 . Te proteins deposited in the brain in these disorders alpha synuclein (AS), Amyloid beta (AB), tau and TDP-43 are transmissible from cell to cell, from one region of the body to another and from humans to susceptible animal hosts 2 . However the agent or agents responsi- ble for the initiation of the protein misfolding is unknown. Prusiner 3 and others have suggested that the initial event is stochastic, but the possibility that it is initiated by environment amyloids requires consideration 4,5 . Te early development of constipation and anosmia and the deposition of aggregated AS in intestinal neurons up to 20 years before diagnosis in PD suggests that the initiating factor comes from the gut (including mouth, nasal passages and intestines) 6 . Tis is also suggested by the early brain pathology in PD in the dorsal motor nucleus of the vagus in the medulla, which is a region afected early in scrapie 7 . Furthermore, infammatory changes are found in neurodegenerative disorders with microgliosis, astrogliosis and activation of infammatory cytokines 1 Dept. of Pathology, case Western Reserve University, cleveland, Ohio, USA. 2 Brown cancer center, University of Louisville School of Medicine, Louisville, Kentucky, USA. 3 Dept. of Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA. 4 Dept. of Oral immunology and infectious Diseases, University of Louisville School of Dentistry, Louisville, Kentucky, USA. 5 Dept. of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, USA. 6 Dept. of Physiology, University of Louisville School of Medicine, Louisville, Kentucky, USA. 7 Dept. of neurology, University of Louisville School of Medicine, Louisville, Kentucky, USA. 8 Dept. of epidemiology and Population Health, University of Louisville School of Public Health, Louisville, Kentucky, USA. 9 Laboratory of experimental neuropathology, University of california, San Diego, california, USA. correspondence and requests for materials should be addressed to R.P.f. (email: robert.friedland@louisville.edu) Received: 08 June 2016 Accepted: 14 September 2016 Published: 06 October 2016 OPEN