Changes in Bacterial Gut Composition in Parkinson’s Disease and Their Metabolic Contribution to Disease Development: A Gut Community Reconstruction Approach

Author:

Forero-Rodríguez Johanna12,Zimmermann Johannes2,Taubenheim Jan2ORCID,Arias-Rodríguez Natalia1,Caicedo-Narvaez Juan David13ORCID,Best Lena2ORCID,Mendieta Cindy V.45ORCID,López-Castiblanco Julieth1ORCID,Gómez-Muñoz Laura Alejandra36,Gonzalez-Santos Janneth7,Arboleda Humberto6ORCID,Fernandez William36,Kaleta Christoph2ORCID,Pinzón Andrés1

Affiliation:

1. Bioinformatics and Systems Biology Research Group, Genetic Institute, Universidad Nacional de Colombia, Bogotá 111321, Colombia

2. Medical Systems Biology Research Group, Institute of Experimental Medicine, Christian-Albrechts-Universität zu Kiel, 24118 Kiel, Germany

3. Neurosciences Research Group, Genetic Institute, Universidad Nacional de Colombia, Bogotá 111321, Colombia

4. PhD Program in Clinical Epidemiology, Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Pontificia Universidad Javeriana, Bogotá 110231, Colombia

5. Department of Nutrition and Biochemistry, Pontificia Universidad Javeriana, Bogotá 110231, Colombia

6. Cell Death Research Group, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogotá 111321, Colombia

7. Structural Biochemistry and Bioinformatics Laboratory, Pontificia Universidad Javeriana, Bogotá 110231, Colombia

Abstract

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease with the major symptoms comprising loss of movement coordination (motor dysfunction) and non-motor dysfunction, including gastrointestinal symptoms. Alterations in the gut microbiota composition have been reported in PD patients vs. controls. However, it is still unclear how these compositional changes contribute to disease etiology and progression. Furthermore, most of the available studies have focused on European, Asian, and North American cohorts, but the microbiomes of PD patients in Latin America have not been characterized. To address this problem, we obtained fecal samples from Colombian participants (n = 25 controls, n = 25 PD idiopathic cases) to characterize the taxonomical community changes during disease via 16S rRNA gene sequencing. An analysis of differential composition, diversity, and personalized computational modeling was carried out, given the fecal bacterial composition and diet of each participant. We found three metabolites that differed in dietary habits between PD patients and controls: carbohydrates, trans fatty acids, and potassium. We identified six genera that changed significantly in their relative abundance between PD patients and controls, belonging to the families Lachnospiraceae, Lactobacillaceae, Verrucomicrobioaceae, Peptostreptococcaceae, and Streptococcaceae. Furthermore, personalized metabolic modeling of the gut microbiome revealed changes in the predicted production of seven metabolites (Indole, tryptophan, fructose, phenylacetic acid, myristic acid, 3-Methyl-2-oxovaleric acid, and N-Acetylneuraminic acid). These metabolites are associated with the metabolism of aromatic amino acids and their consumption in the diet. Therefore, this research suggests that each individual’s diet and intestinal composition could affect host metabolism. Furthermore, these findings open the door to the study of microbiome–host interactions and allow us to contribute to personalized medicine.

Funder

COLCIENCIAS

Pontificia Universidad Javeriana

Sistema General de Regalias with BPIN

German Research Foundation

collaborative research center “Origin and Function of Metaorganisms”

Publisher

MDPI AG

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