@article{5b6583a4330949d391e1f987d087bc17,
title = "Fiber deprivation and microbiome-borne curli shift gut bacterial populations and accelerate disease in a mouse model of Parkinson's disease",
abstract = "Parkinson's disease (PD) is a neurological disorder characterized by motor dysfunction, dopaminergic neuron loss, and alpha-synuclein (αSyn) inclusions. Many PD risk factors are known, but those affecting disease progression are not. Lifestyle and microbial dysbiosis are candidates in this context. Diet-driven gut dysbiosis and reduced barrier function may increase exposure of enteric neurons to toxins. Here, we study whether fiber deprivation and exposure to bacterial curli, a protein cross-seeding with αSyn, individually or together, exacerbate disease in the enteric and central nervous systems of a transgenic PD mouse model. We analyze the gut microbiome, motor behavior, and gastrointestinal and brain pathologies. We find that diet and bacterial curli alter the microbiome and exacerbate motor performance, as well as intestinal and brain pathologies, but to different extents. Our results shed important insights on how diet and microbiome-borne insults modulate PD progression via the gut-brain axis and have implications for lifestyle management of PD.",
keywords = "CP: Microbiology, CP: Neuroscience, Curli, dysbiosis, fiber deprivation, lifestyle, microbiome-gut-brain axis, neurodegeneration, Parkinson's disease, α-synuclein",
author = "Schmit, {Kristopher J.} and Pierre Garcia and Alessia Sciortino and Aho, {Velma T.E.} and {Pardo Rodriguez}, Beatriz and Thomas, {M{\'e}lanie H.} and G{\'e}rardy, {Jean Jacques} and {Bastero Acha}, Irati and Rashi Halder and Camille Cialini and Tony Heurtaux and Irina Ostahi and Busi, {Susheel B.} and L{\'e}a Grandmougin and Tuesday Lowndes and Yogesh Singh and Martens, {Eric C.} and Michel Mittelbronn and Manuel Buttini and Paul Wilmes",
note = "Funding Information: This project received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 863664). The following people were supported by the Luxembourg National Research Fund (FNR): K.J.S. (fellowship AFR 12515776), A.S. (DTU PRIDE17/12244779/PARK-QC), and M.M. (PEARL P16/BM/11192868). The authors thank the Jean Think Foundation (Luxembourg) for support, Wagner Zago (Prothena) for the 11A5 antibody, Matt Chapman (University of Michigan) for the E. coli strains, Luc Buee (University of Lille) for hTau mice, Lennart Mucke (Gladstone Institutes) for J20-hAPP mouse tissues, and the Animal Facility staff at the University of Luxembourg for help. K.J.S. M.B. E.C.M. and P.W. designed the study. K.J.S. P.G. A.S. B.P.R. M.H.T. J.-J.G. I.B.A. C.C. L.G. T.L. and T.H. did the experiments. R.H. performed the 16S rRNA amplicon sequencing. V.T.E.A. analyzed the 16S rRNA gene amplicon sequencing data. K.J.S. A.S. V.T.E.A. P.G. I.O. S.B.B. Y.S. M.M. M.B. and P.W. analyzed and interpreted the data. K.J.S. drafted the paper. M.B. edited the paper. All authors read and approved the final manuscript. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: This project received funding from the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement no. 863664 ). The following people were supported by the Luxembourg National Research Fund (FNR): K.J.S. (fellowship AFR 12515776 ), A.S. ( DTU PRIDE17/12244779/PARK-QC ), and M.M. ( PEARL P16/BM/11192868 ). The authors thank the Jean Think Foundation (Luxembourg) for support, Wagner Zago (Prothena) for the 11A5 antibody, Matt Chapman (University of Michigan) for the E. coli strains, Luc Buee (University of Lille) for hTau mice, Lennart Mucke (Gladstone Institutes) for J20-hAPP mouse tissues, and the Animal Facility staff at the University of Luxembourg for help. Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = sep,
day = "26",
doi = "10.1016/j.celrep.2023.113071",
language = "English",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",
}