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*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article number113071
JournalCell Reports
Volume42
Issue number9
Early online date6 Sept 2023
DOIs
Publication statusPublished - 26 Sept 2023

Keywords

  • CP: Microbiology
  • CP: Neuroscience
  • Curli
  • dysbiosis
  • fiber deprivation
  • lifestyle
  • microbiome-gut-brain axis
  • neurodegeneration
  • Parkinson's disease
  • α-synuclein

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