Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions

Federico Baldini, Johannes Hertel, Estelle Sandt, Cyrille C. Thinnes, Lorieza Neuberger-Castillo, Lukas Pavelka, Fay Betsou, Rejko Krüger, Ines Thiele*, Dominic Allen, Wim Ammerlann, Maike Aurich, Rudi Balling, Peter Banda, Katy Beaumont, Regina Becker, Daniela Berg, Sylvia Binck, Alexandre Bisdorff, Dheeraj BobbiliKathrin Brockmann, Jessica Calmes, Lorieza Castillo, Nico Diederich, Rene Dondelinger, Daniela Esteves, Jean Yves Ferrand, Ronan Fleming, Manon Gantenbein, Thomas Gasser, Piotr Gawron, Lars Geffers, Virginie Giarmana, Enrico Glaab, Clarissa P.C. Gomes, Nikolai Goncharenko, Jérôme Graas, Mariela Graziano, Valentin Groues, Anne Grünewald, Wei Gu, Gaël Hammot, Anne Marie Hanff, Linda Hansen, Maxime Hansen, Hulda Haraldsdöttir, Laurent Heirendt, Sylvia Herbrink, Sascha Herzinger, Michael Heymann, Karsten Hiller, Geraldine Hipp, Michele Hu, Laetitia Huiart, Alexander Hundt, Nadine Jacoby, Jacek Jarosław, Yohan Jaroz, Pierre Kolber, Joachim Kutzera, Zied Landoulsi, Catherine Larue, Roseline Lentz, Inga Lie-Pelt, Robert Liszka, Laura Longhino, Victoria Lorentz, Clare Mackay, Walter Maetzler, Katrin Marcus, Guilherme Marques, Jan Martens, Conny Mathay, Piotr Matyjaszczyk, Patrick May, Francoise Meisch, Myriam Menster, Maura Minelli, Michel Mittelbronn, Brit Mollenhauer, Kathleen Mommaerts, Carlos Moreno, Friedrich Mühlschlegel, Romain Nati, Ulf Nehrbass, Sarah Nickels, Beatrice Nicolai, Jean Paul Nicolay, Alberto Noronha, Wolfgang Oertel, Marek Ostaszewski, Sinthuja Pachchek, Claire Pauly, Magali Perquin, Dorothea Reiter, Isabel Rosety, Kirsten Rump, Venkata Satagopam, Marc Schlesser, Sabine Schmitz, Susanne Schmitz, Reinhard Schneider, Jens Schwamborn, Alexandra Schweicher, Janine Simons, Lara Stute, Christophe Trefois, Jean Pierre Trezzi, Michel Vaillant, Daniel Vasco, Maharshi Vyas, Richard Wade-Martins, Paul Wilmes, Gloria Aguayo

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

73 Citations (Scopus)

Abstract

Background: Parkinson’s disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we addressed this question by an analysis of stool samples from the Luxembourg Parkinson’s Study (n = 147 typical PD cases, n = 162 controls). Results: All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Stool samples from these individuals were first analysed by 16S rRNA gene sequencing. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include the following. Eight genera and seven species changed significantly in their relative abundances between PD patients and healthy controls. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. Particularly, the relative abundances of Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. Furthermore, personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in the predicted secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The predicted microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms. Conclusion: Our results suggest that PD-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism and disease phenotype.

Original languageEnglish
Article number62
JournalBMC Biology
Volume18
Issue number1
DOIs
Publication statusPublished - 9 Jun 2020

Keywords

  • Computational modelling
  • Gut microbiome
  • Metabolic modelling
  • Parkinson’s disease
  • Transsulfuration pathway

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