Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions
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 questi...
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | BMC Biology |
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| Online Access: | http://link.springer.com/article/10.1186/s12915-020-00775-7 |
| _version_ | 1818262177799208960 |
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| author | Federico Baldini Johannes Hertel Estelle Sandt Cyrille C. Thinnes Lorieza Neuberger-Castillo Lukas Pavelka Fay Betsou Rejko Krüger Ines Thiele on behalf of the NCER-PD Consortium |
| author_facet | Federico Baldini Johannes Hertel Estelle Sandt Cyrille C. Thinnes Lorieza Neuberger-Castillo Lukas Pavelka Fay Betsou Rejko Krüger Ines Thiele on behalf of the NCER-PD Consortium |
| author_sort | Federico Baldini |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T18:58:59Z |
| format | Article |
| id | doaj.art-10f7f75169714d4592bd339f6cfa3dd1 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-12T18:58:59Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-10f7f75169714d4592bd339f6cfa3dd12022-12-22T00:15:08ZengBMCBMC Biology1741-70072020-06-0118112110.1186/s12915-020-00775-7Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functionsFederico Baldini0Johannes Hertel1Estelle Sandt2Cyrille C. Thinnes3Lorieza Neuberger-Castillo4Lukas Pavelka5Fay Betsou6Rejko Krüger7Ines Thiele8on behalf of the NCER-PD ConsortiumLuxembourg Centre for Systems Biomedicine (LCSB), University of LuxembourgSchool of Medicine, National University of IrelandIntegrated BioBank of LuxembourgSchool of Medicine, National University of IrelandIntegrated BioBank of LuxembourgLuxembourg Centre for Systems Biomedicine (LCSB), University of LuxembourgIntegrated BioBank of LuxembourgLuxembourg Centre for Systems Biomedicine (LCSB), University of LuxembourgLuxembourg Centre for Systems Biomedicine (LCSB), University of LuxembourgAbstract 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.http://link.springer.com/article/10.1186/s12915-020-00775-7Parkinson’s diseaseGut microbiomeComputational modellingMetabolic modellingTranssulfuration pathway |
| spellingShingle | Federico Baldini Johannes Hertel Estelle Sandt Cyrille C. Thinnes Lorieza Neuberger-Castillo Lukas Pavelka Fay Betsou Rejko Krüger Ines Thiele on behalf of the NCER-PD Consortium Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions BMC Biology Parkinson’s disease Gut microbiome Computational modelling Metabolic modelling Transsulfuration pathway |
| title | Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions |
| title_full | Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions |
| title_fullStr | Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions |
| title_full_unstemmed | Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions |
| title_short | Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions |
| title_sort | parkinson s disease associated alterations of the gut microbiome predict disease relevant changes in metabolic functions |
| topic | Parkinson’s disease Gut microbiome Computational modelling Metabolic modelling Transsulfuration pathway |
| url | http://link.springer.com/article/10.1186/s12915-020-00775-7 |
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