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, Gloria Aguayo, Dominic Allen, Wim Ammerlann, Maike K. Aurich, Rudi Balling, Peter Banda, Katy Beaumont, Regina Becker, Daniela Berg, Sylvia Binck, Alexandre Bisdorff, Dheeraj Reddy Bobbili, Kathrin Brockmann, Jessica Calmes, Lorieza Castillo, Nico J. Diederich, Rene Dondelinger, Daniela Esteves, Jean-Yves Ferrand, Ronan M. T. Fleming, Manon Gantenbein, Thomas Gasser, Piotr Gawron, Lars Geffers, Virginie Giarmana, Enrico Glaab, Clarissa P. C. Gomes, Nikolai Goncharenko, Jérôme Graas, Mariela Graziano, Valentin Grouès, Anne Grünewald, Wei Gu, Gaël Hammot, Anne-Marie Hanff, Linda Hansen, Maxime Hansen, Hulda S. Haraldsdóttir, Laurent Heirendt, Sylvia Herbrink, Sascha Herzinger, Michaël Heymann, Karsten Hiller, Géraldine Hipp, Michele Hu, Laëtitia Huiart, Alexander Hundt, Nadine Jacoby, Jacek Jarosław, Yohan Jaroz, Pierre Kolber, Joachim Kutzera, Zied Landoulsi, Catherine Larue, Roseline Lentz, Inga Liepelt, Robert Liszka, Laura Longhino, Victoria Lorentz, Clare E. Mackay, Walter Maetzler, Katrin Marcus, Guilherme Fernandes Marques, Jan Martens, Conny Mathay, Piotr Matyjaszczyk, Patrick May, Françoise Meisch, Myriam Menster, Maura Minelli, Michel Mittelbronn, Brit Mollenhauer, Kathleen Mommaerts, Carlos S. Moreno, Friedrich Mühlschlegel, Romain Nati, Ulf Nehrbass, Sarah Nickels, Béatrice Nicolai, Jean-Paul Nicolay, Alberto Noronha, Wolfgang H. Oertel, Marek Ostaszewski, Sinthuja Pachchek, Claire Pauly, Magali Perquin, Dorothea Reiter, Isabel Rosety, Kirsten Rump, Venkata Satagopam, Marc Schlesser
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.