RT Journal Article
SR Electronic
T1 Parkinson’s disease-associated alterations of the gut microbiome can invoke disease-relevant metabolic changes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 691030
DO 10.1101/691030
A1 Federico Baldini
A1 Johannes Hertel
A1 Estelle Sandt
A1 Cyrille C. Thinnes
A1 Lorieza Neuberger-Castillo
A1 Lukas Pavelka
A1 Fay Betsou
A1 Rejko Krüger
A1 Ines Thiele
A1 on behalf of the NCER-PD Consortium
YR 2019
UL http://biorxiv.org/content/early/2019/07/02/691030.abstract
AB 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 first analysed the gut microbiome of patients and healthy controls by 16S rRNA gene sequencing of stool samples from the Luxembourg Parkinson’s study (n=147 typical PD cases, n=162 controls). All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. 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: 1. eight genera and nine species changed significantly in their relative abundances between PD patients and healthy controls. 2. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. The relative abundances of Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. In contrast, dopaminergic medication had no detectable effect on the PD microbiome composition. 3. Personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms and attributed to individual bacteria, such as Akkermansia muciniphila and Bilophila wardswarthia. Our results suggest that PD-associated alterations of gut microbiome could translate into functional differences affecting host metabolism and disease phenotype.