Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions
Authors: Baldini Federico , Hertel Johannes , Sandt Estelle , Thinnes Cyrille C. , Neuberger-Castillo Lorieza , Pavelka Lukas , Betsou Fay , Krüger Rejko , Thiele Ines ,   on behalf of the NCER-PD Consortium, Aguayo Gloria , Allen Dominic , Ammerlann Wim , Aurich Maike , Balling Rudi , Banda Peter , Beaumont Katy , Becker Regina , Berg Daniela , Binck Sylvia , Bisdorff Alexandre , Bobbili Dheeraj , Brockmann Kathrin , Calmes Jessica , Castillo Lorieza , Diederich Nico , Dondelinger Rene , Esteves Daniela , Ferrand Jean-Yves , Fleming Ronan , Gantenbein Manon , Gasser Thomas , Gawron Piotr , Geffers Lars , Giarmana Virginie , Glaab Enrico , Gomes Clarissa P. C. , Goncharenko Nikolai , Graas Jérôme , Graziano Mariela , Groues Valentin , Grünewald Anne , Gu Wei , Hammot Gaël , Hanff Anne-Marie , Hansen Linda , Hansen Maxime , Haraldsdöttir Hulda , Heirendt Laurent , Herbrink Sylvia , Herzinger Sascha , Heymann Michael , Hiller Karsten , Hipp Geraldine , Hu Michele , Huiart Laetitia , Hundt Alexander , Jacoby Nadine , Jarosław Jacek , Jaroz Yohan , Kolber Pierre , Kutzera Joachim , Landoulsi Zied , Larue Catherine , Lentz Roseline , Liepelt Inga , Liszka Robert , Longhino Laura , Lorentz Victoria , Mackay Clare , Maetzler Walter , Marcus Katrin , Marques Guilherme , Martens Jan , Mathay Conny , Matyjaszczyk Piotr , May Patrick , Meisch Francoise , Menster Myriam , Minelli Maura , Mittelbronn Michel , Mollenhauer Brit , Mommaerts Kathleen , Moreno Carlos , Mühlschlegel Friedrich , Nati Romain , Nehrbass Ulf , Nickels Sarah , Nicolai Beatrice , Nicolay Jean-Paul , Noronha Alberto , Oertel Wolfgang , Ostaszewski Marek , Pachchek Sinthuja , Pauly Claire , Perquin Magali , Reiter Dorothea , Rosety Isabel , Rump Kirsten , Satagopam Venkata , Schlesser Marc , Schmitz Sabine , Schmitz Susanne , Schneider Reinhard , Schwamborn Jens , Schweicher Alexandra , Simons Janine , Stute Lara , Trefois Christophe , Trezzi Jean-Pierre , Vaillant Michel , Vasco Daniel , Vyas Maharshi , Wade-Martins Richard , Wilmes Paul 
Published: June 2020

AbstractBackgroundParkinson’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).ResultsAll 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 ofBilophilaandParaprevotellawere 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.ConclusionOur results suggest that PD-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism and disease phenotype.