@article{909f654e021f473786b521e145638800,
title = "Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson's disease",
abstract = "Parkinson's disease (PD) is the most common progressive neurological disorder compromising motor functions. However, nonmotor symptoms, such as gastrointestinal (GI) dysfunction, precede those affecting movement. Evidence of an early involvement of the GI tract and enteric nervous system highlights the need for better understanding of the role of gut microbiota in GI complications in PD. Here, we investigate the gut microbiome of patients with PD using metagenomics and serum metabolomics. We integrate these data using metabolic modeling and construct an integrative correlation network giving insight into key microbial species linked with disease severity, GI dysfunction, and age of patients with PD. Functional analysis reveals an increased microbial capability to degrade mucin and host glycans in PD. Personalized community-level metabolic modeling reveals the microbial contribution to folate deficiency and hyperhomocysteinemia observed in patients with PD. The metabolic modeling approach could be applied to uncover gut microbial metabolic contributions to PD pathophysiology. Rosario et al. reveal the role of gut microbiome in Parkinson's disease (PD) through functional and compositional analysis and genome-scale metabolic modeling. Microbial capability of mucin and host glycans degradation is associated with disease severity. Gut-community metabolic modeling reveals the bacterial contribution to folic acid deficit and hyperhomocysteinemia in PD.",
keywords = "gut microbiota, gut-brain axis, metabolic modeling, metagenomics, Parkinson's disease",
author = "Dorines Rosario and Gholamreza Bidkhori and Sunjae Lee and Janis Bedarf and Falk Hildebrand and {Le Chatelier}, Emmanuelle and Mathias Uhlen and Ehrlich, {Stanislav Dusko} and Gordon Proctor and Ullrich W{\"u}llner and Adil Mardinoglu and Saeed Shoaie",
note = "Funding Information: This study was supported by Engineering and Physical Sciences Research Council (EPSRC) ( EP/S001301/1 ), Biotechnology Biological Sciences Research Council (BBSRC) ( BB/S016899/1 ), and Science for Life Laboratory . F.H.{\textquoteright}s salary is funded by the BBSrC Institute Strategic Programme Gut Microbes and Health BB/r012490/1 and its constituent project BBS/e/F/000Pr10355 . We are thankful to the entire staff of the Translational Systems Biology, Centre for Host-Microbiome Interactions, the Science for Life Laboratory, and Metagenopolis. The authors acknowledge the Swedish National Infrastructure for Computing at SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under projects SNIC 2019/3-226 and SNIC 2020/5-222 . The authors also acknowledge King{\textquoteright}s College London computational infrastructure facility, Rosalind ( https://rosalind.kcl.ac.uk ), for high-performance computing. J.B. received honoraria for scientific presentations and travel grants from IPSEN Pharma Germany and Merz Pharmaceuticals Germany and is supported by the ParkinsonFonds Deutschland gGmbH and the Hilde Ulrich Stiftung for Parkinson{\textquoteright}s Research, Germany . Funding Information: This study was supported by Engineering and Physical Sciences Research Council (EPSRC) (EP/S001301/1), Biotechnology Biological Sciences Research Council (BBSRC) (BB/S016899/1), and Science for Life Laboratory. F.H.?s salary is funded by the BBSrC Institute Strategic Programme Gut Microbes and Health BB/r012490/1 and its constituent project BBS/e/F/000Pr10355. We are thankful to the entire staff of the Translational Systems Biology, Centre for Host-Microbiome Interactions, the Science for Life Laboratory, and Metagenopolis. The authors acknowledge the Swedish National Infrastructure for Computing at SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under projects SNIC 2019/3-226 and SNIC 2020/5-222. The authors also acknowledge King's College London computational infrastructure facility, Rosalind (https://rosalind.kcl.ac.uk), for high-performance computing. J.B. received honoraria for scientific presentations and travel grants from IPSEN Pharma Germany and Merz Pharmaceuticals Germany and is supported by the ParkinsonFonds Deutschland gGmbH and the Hilde Ulrich Stiftung for Parkinson's Research, Germany. S.S. and A.M. conceived and supervised the study. D.R. S.L. and E.L.C. performed the microbiome analysis. D.R. performed the integration of multi-omics data and modeling. G.B. reconstructed and refined the individual and community GEMs. J.B. F.H. and U.W. assisted in serum metabolomics and clinical metadata analysis. D.R. wrote the manuscript. S.S. S.D.E. M.U. and U.W. provided critical comments and feedback. All authors have revised and contributed to the final version. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = mar,
day = "2",
doi = "10.1016/j.celrep.2021.108807",
language = "English",
volume = "34",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier BV",
number = "9",
}