Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer's disease.

Humans Alzheimer Disease / genetics Microbiota / genetics Gastrointestinal Microbiome / genetics Genomics Formates
Alzheimer’s disease Co-metabolism Constraint-based modelling Formate Host-microbiome Metabolic modelling Metabolomics Microbiome Pathways

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
13 03 2024
Historique:
received: 29 08 2023
accepted: 29 02 2024
medline: 15 3 2024
pubmed: 14 3 2024
entrez: 14 3 2024
Statut: epublish

Résumé

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. Notably, AD individuals displayed diminished formate microbial secretion in these 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.

Identifiants

DOI: 10.1038/s41598-024-55960-3 PMID: 38480804 PMC: PMC10937638
pubmed: 38480804
doi: 10.1038/s41598-024-55960-3
pii: 10.1038/s41598-024-55960-3
pmc: PMC10937638
doi:

Substances chimiques

Formates 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

6095

Subventions

Organisme : NIGMS NIH HHS
ID : T32 GM081061
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG069901
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG063744
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054047
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG021155
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG027161
Pays : United States
Organisme : NINDS NIH HHS
ID : F99 NS130922
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059093
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG061359
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG070973
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG037639
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG046171
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057452
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062715
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG058942
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG051550
Pays : United States

Informations de copyright

© 2024. The Author(s).

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Auteurs

Filippo Martinelli (F)

School of Medicine, University of Galway, Galway, Ireland.
The Ryan Institute, University of Galway, Galway, Ireland.

Almut Heinken (A)

School of Medicine, University of Galway, Galway, Ireland.
The Ryan Institute, University of Galway, Galway, Ireland.
Inserm UMRS 1256 NGERE, University of Lorraine, Nancy, France.

Ann-Kristin Henning (AK)

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

Maria A Ulmer (MA)

Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

Tim Hensen (T)

School of Medicine, University of Galway, Galway, Ireland.
The Ryan Institute, University of Galway, Galway, Ireland.

Antonio González (A)

Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.

Matthias Arnold (M)

Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Department of Psychiatry and Behavioural Sciences, Duke University, Durham, NC, USA.

Sanjay Asthana (S)

Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.

Kathrin Budde (K)

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

Corinne D Engelman (CD)

Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

Mehrbod Estaki (M)

Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.

Hans-Jörgen Grabe (HJ)

German Center of Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.

Margo B Heston (MB)

Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.

Sterling Johnson (S)

Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.

Gabi Kastenmüller (G)

Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

Cameron Martino (C)

Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.

Daniel McDonald (D)

Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.

Federico E Rey (FE)

Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.

Ingo Kilimann (I)

German Center of Neurodegenerative Diseases (DZNE), Rostock, Germany.
Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany.

Olive Peters (O)

German Center of Neurodegenerative Diseases (DZNE), Berlin, Germany.
Department of Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Xiao Wang (X)

Department of Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Eike Jakob Spruth (EJ)

German Center of Neurodegenerative Diseases (DZNE), Berlin, Germany.
Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany.

Anja Schneider (A)

German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
Department of Neurology, University of Bonn, Bonn, Germany.

Klaus Fliessbach (K)

German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
Department of Neurology, University of Bonn, Bonn, Germany.

Jens Wiltfang (J)

German Center of Neurodegenerative Diseases (DZNE), Goettingen, Germany.
Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany.
Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal.

Niels Hansen (N)

Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany.

Wenzel Glanz (W)

German Center of Neurodegenerative Diseases (DZNE), Magdeburg, Germany.

Katharina Buerger (K)

German Center of Neurodegenerative Diseases (DZNE), Munich, Germany.
Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.

Daniel Janowitz (D)

Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.

Christoph Laske (C)

German Center of Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Section for Dementia Research, Hertie Institute for Clinical Brain Research, Tübingen, Germany.
Section for Dementia Research, Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.

Matthias H Munk (MH)

German Center of Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Section for Dementia Research, Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.

Annika Spottke (A)

German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
Department of Neurology, University of Bonn, Bonn, Germany.

Nina Roy (N)

German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.

Matthias Nauck (M)

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, Greifswald, Germany.

Stefan Teipel (S)

German Center of Neurodegenerative Diseases (DZNE), Rostock, Germany.
Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany.

Rob Knight (R)

Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.
Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
Shu Chien-Gene Lay Department of Engineering, University of California San Diego, La Jolla, CA, USA.
Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, CA, USA.

Rima F Kaddurah-Daouk (RF)

Department of Medicine, Duke University Medical Center, Durham, USA.

Barbara B Bendlin (BB)

Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.

Johannes Hertel (J)

School of Medicine, University of Galway, Galway, Ireland. Johannes.Hertel@med.uni-greifswald.de.
DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, Greifswald, Germany. Johannes.Hertel@med.uni-greifswald.de.

Ines Thiele (I)

School of Medicine, University of Galway, Galway, Ireland. ines.thiele@universityofgalway.ie.
The Ryan Institute, University of Galway, Galway, Ireland. ines.thiele@universityofgalway.ie.
School of Microbiology, University of Galway, Galway, Ireland. ines.thiele@universityofgalway.ie.
APC Microbiome Ireland, Cork, Ireland. ines.thiele@universityofgalway.ie.

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