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

Author

Baldini, Federico, Hertel, Johannes, Sandt, Estelle, Thinnes, Cyrille C., Neuberger-Castillo, Lorieza, Pavelka, Lukas, Betsou, Fay, Krüger, Rejko, Thiele, Ines, 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, and Wilmes, Paul

Subjects
Male, Systemic disease, Parkinson's disease, Physiology, Luxembourg, Plant Science, Disease, Transsulfuration pathway, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Structural Biology, RNA, Ribosomal, 16S, Pantothenic acid, medicine, Humans, Microbiome, lcsh:QH301-705.5, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Aged, Metabolic modelling, 0303 health sciences, Gut microbiome, Methionine, Dopaminergic, Parkinson Disease, Cell Biology, Middle Aged, medicine.disease, 3. Good health, Gastrointestinal Microbiome, RNA, Bacterial, chemistry, Computational modelling, lcsh:Biology (General), Case-Control Studies, Parkinson’s disease, Female, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, Developmental Biology, Biotechnology, Research Article
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.

Published
2020
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7. Contributing Factors and Evolution of Impulse Control Disorder in the Luxembourg Parkinson Cohort.

Author

Binck, Sylvia, Pauly, Claire, Vaillant, Michel, Hipp, Geraldine, Gantenbein, Manon, Krüger, Rejko, Diederich, Nico J., Binck, Sylvia, Pauly, Claire, Vaillant, Michel, Hipp, Geraldine, Gantenbein, Manon, Krüger, Rejko, and Diederich, Nico J.

Abstract

Background: To establish the frequency of impulse control disorder (ICD) in Parkinson's disease (PD). Methods: Within the Luxembourg Parkinson's Study, PD patients were evaluated for ICD presence (score ≥ 1 on MDS-UPDRS I item 1.6), use of dopamine agonists (DA) and other medications. Results: 470 patients were enrolled. Among 217 patients without DA use, 6.9% scored positive for ICD, vs. 15.4% among 253 patients with DA use (p = 0.005). The regression analysis showed that age at PD diagnosis had only a minor impact on ICD occurrence, while there was no influence by gender or co-medications. The longitudinal study over 2 years in 156 patients demonstrated increasing ICD frequency in DA users (p = 0.005). Conclusion: This large and non-interventional study confirms that PD patients with DA treatment show higher frequency of ICD than patients without DA use. It newly demonstrates that ICD can develop independently from age, gender, or co-medications.

Published
2020

9. The Luxembourg Parkinson’s Study: A Comprehensive Approach for Stratification and Early Diagnosis

Author

Hipp, Geraldine, primary, Vaillant, Michel, additional, Diederich, Nico J., additional, Roomp, Kirsten, additional, Satagopam, Venkata P., additional, Banda, Peter, additional, Sandt, Estelle, additional, Mommaerts, Kathleen, additional, Schmitz, Sabine K., additional, Longhino, Laura, additional, Schweicher, Alexandra, additional, Hanff, Anne-Marie, additional, Nicolai, Béatrice, additional, Kolber, Pierre, additional, Reiter, Dorothea, additional, Pavelka, Lukas, additional, Binck, Sylvia, additional, Pauly, Claire, additional, Geffers, Lars, additional, Betsou, Fay, additional, Gantenbein, Manon, additional, Klucken, Jochen, additional, Gasser, Thomas, additional, Hu, Michele T., additional, Balling, Rudi, additional, and Krüger, Rejko, additional

Published
2018
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10. Aiming for study comparability in Parkinson's disease: Proposal for a modular set of biomarker assessments to be used in longitudinal studies

Author

Lerche, Stefanie, Heinzel, Sebastian, Alves, Guido W., Barone, Paulo, Ben-Shlomo, Yoav, Berendse, Henk, Bloem, Bastiaan R., Burn, David, Dodel, Richard, Grosset, Donald G., Hipp, Geraldine, Hu, Michele T., Kasten, Meike, Kruger, Rejko, Liepelt-Scarfone, Inga, Maetzler, Walter, Moccia, Marcello, Mollenhauer, Brit, Oertel, Wolfgang, Roeben, Benjamin, Walter, Uwe, Wirderfelt, Karin, and Berg, Daniela

Abstract

No abstract available.

Published
2016

12. Discriminative power of different nonmotor signs in early Parkinson's disease. A case-control study

Author

Diederich, Nico, Pieri, Vannina, Hipp, Geraldine, Rufra, Olivier, Blyth, Sara, Vaillant, Michel, Diederich, Nico, Pieri, Vannina, Hipp, Geraldine, Rufra, Olivier, Blyth, Sara, and Vaillant, Michel

Abstract

The objective of this study was to evaluate the discriminative power of different nonmotor signs for early diagnosis of Parkinson's disease (PD). Thirty patients with PD with

Published
2010

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