Scientific Reports (Mar 2024)
Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease
- 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
Affiliations
- Filippo Martinelli
- School of Medicine, University of Galway
- Almut Heinken
- School of Medicine, University of Galway
- Ann-Kristin Henning
- Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald
- Maria A. Ulmer
- Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health
- Tim Hensen
- School of Medicine, University of Galway
- Antonio González
- Department of Pediatrics, University of California San Diego
- Matthias Arnold
- Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health
- Sanjay Asthana
- Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin
- Kathrin Budde
- Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald
- Corinne D. Engelman
- Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health
- Mehrbod Estaki
- Department of Pediatrics, University of California San Diego
- Hans-Jörgen Grabe
- German Center of Neurodegenerative Diseases (DZNE)
- Margo B. Heston
- Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin
- Sterling Johnson
- Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin
- Gabi Kastenmüller
- Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health
- Cameron Martino
- Department of Pediatrics, University of California San Diego
- Daniel McDonald
- Department of Pediatrics, University of California San Diego
- Federico E. Rey
- Department of Bacteriology, University of Wisconsin-Madison
- Ingo Kilimann
- German Center of Neurodegenerative Diseases (DZNE)
- Olive Peters
- German Center of Neurodegenerative Diseases (DZNE)
- Xiao Wang
- Department of Psychiatry, Charité-Universitätsmedizin Berlin
- Eike Jakob Spruth
- German Center of Neurodegenerative Diseases (DZNE)
- Anja Schneider
- German Center of Neurodegenerative Diseases (DZNE)
- Klaus Fliessbach
- German Center of Neurodegenerative Diseases (DZNE)
- Jens Wiltfang
- German Center of Neurodegenerative Diseases (DZNE)
- Niels Hansen
- Department of Psychiatry and Psychotherapy, University of Goettingen
- Wenzel Glanz
- German Center of Neurodegenerative Diseases (DZNE)
- Katharina Buerger
- German Center of Neurodegenerative Diseases (DZNE)
- Daniel Janowitz
- Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich
- Christoph Laske
- German Center of Neurodegenerative Diseases (DZNE)
- Matthias H. Munk
- German Center of Neurodegenerative Diseases (DZNE)
- Annika Spottke
- German Center of Neurodegenerative Diseases (DZNE)
- Nina Roy
- German Center of Neurodegenerative Diseases (DZNE)
- Matthias Nauck
- DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine
- Stefan Teipel
- German Center of Neurodegenerative Diseases (DZNE)
- Rob Knight
- Department of Computer Science and Engineering, University of California San Diego
- Rima F. Kaddurah-Daouk
- Department of Medicine, Duke University Medical Center
- Barbara B. Bendlin
- Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin
- Johannes Hertel
- School of Medicine, University of Galway
- Ines Thiele
- School of Medicine, University of Galway
- DOI
- https://doi.org/10.1038/s41598-024-55960-3
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 14
Abstract
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.
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