[en] 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.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB): Eco-Systems Biology (Wilmes Group)
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
SCHMIT, Kristopher ✱; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Systems Ecology > Team Paul WILMES
GARCIA, Pierre ✱; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology
SCIORTINO, Alessia ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Neuropathology > Team Michel MITTELBRONN
AHO, Velma ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Systems Ecology > Team Paul WILMES
Pardo Rodriguez, Beatriz; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg, Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg
THOMAS, Melanie ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Systems Ecology > Team Paul WILMES
GERARDY, Jean-Jacques ; University of Luxembourg ; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg, National Center of Pathology, Laboratoire National de Santé, 3555 Dudelange, Luxembourg
Bastero Acha, Irati; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg, Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg
HALDER, Rashi ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services > Sequencing Platform
CIALINI, Camille ; University of Luxembourg ; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg, Department of Cancer Research, Luxembourg Institute of Health, 1526 Luxembourg, Luxembourg
HEURTAUX, Tony ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Ostahi, Irina; National Center of Pathology, Laboratoire National de Santé, 3555 Dudelange, Luxembourg
BUSI, Susheel Bhanu ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Systems Ecology > Team Paul WILMES
Grandmougin, Léa; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg
LOWNDES, Tuesday ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology
Singh, Yogesh; Institute for Medical Genetics and Applied Genomics, Hospital University Tubingen, 72076 Tubingen, Germany
Martens, Eric C; Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
MITTELBRONN, Michel ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology
BUTTINI, Manuel ✱; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology
WILMES, Paul ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology
H2020 - 863664 - ExpoBiome - Deciphering the impact of exposures from the gut microbiome-derived molecular complex in human health and disease
FnR Project :
DTU PRIDE17/12244779/PARK-QC - PEARL P16/BM/11192868 -
Name of the research project :
Deciphering the impact of exposures from the gut microbiome-derived molecular complex in human health and disease
Funders :
Jean Think Foundation Union Européenne
Funding text :
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.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.
Commentary :
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
helpK.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.
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