Fiber deprivation and microbiome-borne curli shift gut bacterial populations and accelerate disease in a mouse model of Parkinson’s disease
Kristopher J. Schmit,
Pierre Garcia,
Alessia Sciortino,
Velma T.E. Aho,
Beatriz Pardo Rodriguez,
Mélanie H. Thomas,
Jean-Jacques Gérardy,
Irati Bastero Acha,
Rashi Halder,
Camille Cialini,
Tony Heurtaux,
Irina Ostahi,
Susheel B. Busi,
Léa Grandmougin,
Tuesday Lowndes,
Yogesh Singh,
Eric C. Martens,
Michel Mittelbronn,
Manuel Buttini,
Paul Wilmes
Affiliations
Kristopher J. Schmit
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Institute for Medical Genetics and Applied Genomics, Hospital University Tubingen, 72076 Tubingen, Germany; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg; Corresponding author
Pierre Garcia
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg
Alessia Sciortino
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg
Velma T.E. Aho
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg
Beatriz Pardo Rodriguez
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg
Mélanie H. Thomas
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg
Jean-Jacques Gérardy
Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg; National Center of Pathology, Laboratoire National de Santé, 3555 Dudelange, Luxembourg
Irati Bastero Acha
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg
Rashi Halder
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg
Camille Cialini
Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg; Department of Cancer Research, Luxembourg Institute of Health, 1526 Luxembourg, Luxembourg
Tony Heurtaux
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg; Department of Life Sciences and Medicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg
Irina Ostahi
National Center of Pathology, Laboratoire National de Santé, 3555 Dudelange, Luxembourg
Susheel B. Busi
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg
Léa Grandmougin
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg
Tuesday Lowndes
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg
Yogesh Singh
Institute for Medical Genetics and Applied Genomics, Hospital University Tubingen, 72076 Tubingen, Germany
Eric C. Martens
Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Michel Mittelbronn
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg; National Center of Pathology, Laboratoire National de Santé, 3555 Dudelange, Luxembourg; Department of Cancer Research, Luxembourg Institute of Health, 1526 Luxembourg, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, 4365 Esch-sur-Alzette, Luxembourg
Manuel Buttini
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Luxembourg Center of Neuropathology, 3555 Dudelange, Luxembourg
Paul Wilmes
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, 4365 Esch-sur-Alzette, Luxembourg; Corresponding author
Summary: 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.
