Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease
Abstract In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased fo...
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2024-03-01
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| author | Filippo Martinelli Almut Heinken Ann-Kristin Henning Maria A. Ulmer Tim Hensen Antonio González Matthias Arnold Sanjay Asthana Kathrin Budde Corinne D. Engelman Mehrbod Estaki Hans-Jörgen Grabe Margo B. Heston Sterling Johnson Gabi Kastenmüller Cameron Martino Daniel McDonald Federico E. Rey Ingo Kilimann Olive Peters Xiao Wang Eike Jakob Spruth Anja Schneider Klaus Fliessbach Jens Wiltfang Niels Hansen Wenzel Glanz Katharina Buerger Daniel Janowitz Christoph Laske Matthias H. Munk Annika Spottke Nina Roy Matthias Nauck Stefan Teipel Rob Knight Rima F. Kaddurah-Daouk Barbara B. Bendlin Johannes Hertel Ines Thiele |
| author_facet | Filippo Martinelli Almut Heinken Ann-Kristin Henning Maria A. Ulmer Tim Hensen Antonio González Matthias Arnold Sanjay Asthana Kathrin Budde Corinne D. Engelman Mehrbod Estaki Hans-Jörgen Grabe Margo B. Heston Sterling Johnson Gabi Kastenmüller Cameron Martino Daniel McDonald Federico E. Rey Ingo Kilimann Olive Peters Xiao Wang Eike Jakob Spruth Anja Schneider Klaus Fliessbach Jens Wiltfang Niels Hansen Wenzel Glanz Katharina Buerger Daniel Janowitz Christoph Laske Matthias H. Munk Annika Spottke Nina Roy Matthias Nauck Stefan Teipel Rob Knight Rima F. Kaddurah-Daouk Barbara B. Bendlin Johannes Hertel Ines Thiele |
| author_sort | Filippo Martinelli |
| collection | DOAJ |
| description | Abstract In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. We predicted microbial formate as well as other microbial metabolites, which could alter urine formate production in the host-microbiome personalised models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management. |
| format | Article |
| id | doaj-art-9445c1dce1a8438ba72e79a6a96af1f9 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-9445c1dce1a8438ba72e79a6a96af1f92024-11-17T12:23:12ZengNature PortfolioScientific Reports2045-23222024-03-0114111410.1038/s41598-024-55960-3Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s diseaseFilippo Martinelli0Almut Heinken1Ann-Kristin Henning2Maria A. Ulmer3Tim Hensen4Antonio González5Matthias Arnold6Sanjay Asthana7Kathrin Budde8Corinne D. Engelman9Mehrbod Estaki10Hans-Jörgen Grabe11Margo B. Heston12Sterling Johnson13Gabi Kastenmüller14Cameron Martino15Daniel McDonald16Federico E. Rey17Ingo Kilimann18Olive Peters19Xiao Wang20Eike Jakob Spruth21Anja Schneider22Klaus Fliessbach23Jens Wiltfang24Niels Hansen25Wenzel Glanz26Katharina Buerger27Daniel Janowitz28Christoph Laske29Matthias H. Munk30Annika Spottke31Nina Roy32Matthias Nauck33Stefan Teipel34Rob Knight35Rima F. Kaddurah-Daouk36Barbara B. Bendlin37Johannes Hertel38Ines Thiele39School of Medicine, University of GalwaySchool of Medicine, University of GalwayInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine GreifswaldInstitute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental HealthSchool of Medicine, University of GalwayDepartment of Pediatrics, University of California San DiegoInstitute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental HealthWisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of WisconsinInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine GreifswaldDepartment of Population Health Sciences, University of Wisconsin School of Medicine and Public HealthDepartment of Pediatrics, University of California San DiegoGerman Center of Neurodegenerative Diseases (DZNE)Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of WisconsinWisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of WisconsinInstitute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental HealthDepartment of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoDepartment of Bacteriology, University of Wisconsin-MadisonGerman Center of Neurodegenerative Diseases (DZNE)German Center of Neurodegenerative Diseases (DZNE)Department of Psychiatry, Charité-Universitätsmedizin BerlinGerman Center of Neurodegenerative Diseases (DZNE)German Center of Neurodegenerative Diseases (DZNE)German Center of Neurodegenerative Diseases (DZNE)German Center of Neurodegenerative Diseases (DZNE)Department of Psychiatry and Psychotherapy, University of GoettingenGerman Center of Neurodegenerative Diseases (DZNE)German Center of Neurodegenerative Diseases (DZNE)Institute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichGerman Center of Neurodegenerative Diseases (DZNE)German Center of Neurodegenerative Diseases (DZNE)German Center of Neurodegenerative Diseases (DZNE)German Center of Neurodegenerative Diseases (DZNE)DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University MedicineGerman Center of Neurodegenerative Diseases (DZNE)Department of Computer Science and Engineering, University of California San DiegoDepartment of Medicine, Duke University Medical CenterWisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of WisconsinSchool of Medicine, University of GalwaySchool of Medicine, University of GalwayAbstract In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. We predicted microbial formate as well as other microbial metabolites, which could alter urine formate production in the host-microbiome personalised models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.https://doi.org/10.1038/s41598-024-55960-3Alzheimer’s diseaseMetabolic modellingConstraint-based modellingMicrobiomeFormateMetabolomics |
| spellingShingle | Filippo Martinelli Almut Heinken Ann-Kristin Henning Maria A. Ulmer Tim Hensen Antonio González Matthias Arnold Sanjay Asthana Kathrin Budde Corinne D. Engelman Mehrbod Estaki Hans-Jörgen Grabe Margo B. Heston Sterling Johnson Gabi Kastenmüller Cameron Martino Daniel McDonald Federico E. Rey Ingo Kilimann Olive Peters Xiao Wang Eike Jakob Spruth Anja Schneider Klaus Fliessbach Jens Wiltfang Niels Hansen Wenzel Glanz Katharina Buerger Daniel Janowitz Christoph Laske Matthias H. Munk Annika Spottke Nina Roy Matthias Nauck Stefan Teipel Rob Knight Rima F. Kaddurah-Daouk Barbara B. Bendlin Johannes Hertel Ines Thiele Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease Scientific Reports Alzheimer’s disease Metabolic modelling Constraint-based modelling Microbiome Formate Metabolomics |
| title | Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease |
| title_full | Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease |
| title_fullStr | Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease |
| title_full_unstemmed | Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease |
| title_short | Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease |
| title_sort | whole body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in alzheimer s disease |
| topic | Alzheimer’s disease Metabolic modelling Constraint-based modelling Microbiome Formate Metabolomics |
| url | https://doi.org/10.1038/s41598-024-55960-3 |
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