Evidence map›Paper›PMID 38480804›Full record

ArticleScientific reports2024

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 and 30 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Reconstruction of human metabolic models with large language models.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Article
  6. Open medicine (Warsaw, Poland) · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Gut microbiome compositional and functional features associate with Alzheimer's disease pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  11. Metabolic modeling of host-microbe interactions.Computational and structural biotechnology journal · 2025
    Review
  12. Article
  13. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

40 authors at 13 institutions in 5 countries.

Filippo MartinelliSchool of Medicine, University of Galway, Galway, Ireland.
Almut HeinkenSchool of Medicine, University of Galway, Galway, Ireland.
Ann-Kristin HenningInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Maria A UlmerInstitute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Tim HensenSchool of Medicine, University of Galway, Galway, Ireland.
Antonio GonzálezDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Matthias ArnoldInstitute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Sanjay AsthanaWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.
Kathrin BuddeInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Corinne D EngelmanDepartment of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Mehrbod EstakiDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Hans-Jörgen GrabeGerman Center of Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
Margo B HestonWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.
Sterling JohnsonWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.
Gabi KastenmüllerInstitute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Cameron MartinoDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Daniel McDonaldDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Federico E ReyDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
Ingo KilimannGerman Center of Neurodegenerative Diseases (DZNE), Rostock, Germany.
Olive PetersGerman Center of Neurodegenerative Diseases (DZNE), Berlin, Germany.
Xiao WangDepartment of Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Eike Jakob SpruthGerman Center of Neurodegenerative Diseases (DZNE), Berlin, Germany.
Anja SchneiderGerman Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
Klaus FliessbachGerman Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
Jens WiltfangGerman Center of Neurodegenerative Diseases (DZNE), Goettingen, Germany.
Niels HansenDepartment of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany.
Wenzel GlanzGerman Center of Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Katharina BuergerGerman Center of Neurodegenerative Diseases (DZNE), Munich, Germany.
Daniel JanowitzInstitute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
Christoph LaskeGerman Center of Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Matthias H MunkGerman Center of Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Annika SpottkeGerman Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
Nina RoyGerman Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
Matthias NauckInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Stefan TeipelGerman Center of Neurodegenerative Diseases (DZNE), Rostock, Germany.
Rob KnightDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Rima F Kaddurah-DaoukDepartment of Medicine, Duke University Medical Center, Durham, USA.
Barbara B BendlinWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, USA.
Johannes Hertel *School of Medicine, University of Galway, Galway, Ireland. Johannes.Hertel@med.uni-greifswald.de.
Ines Thiele *School of Medicine, University of Galway, Galway, Ireland. ines.thiele@universityofgalway.ie.
German Center for Neurodegenerative Diseases · DEUniversity of Wisconsin–Madison · USUniversity of California San Diego · USOllscoil na Gaillimhe – University of Galway · IEUniversitätsmedizin Greifswald · DEUniversity of Bonn · DEHelmholtz Zentrum München · DECharité - Universitätsmedizin Berlin · DEDuke Medical Center · USDuke University · USInserm · FRLMU Klinikum · DEUniversity of Göttingen · DE

Funding

Project 4 - Mechanistic studies on the role of the gut microbiome in models for Alzheimer's diseaseU19AG063744 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Rima F Kaddurah-Daouk · 2019 to 2026
$54.1M
Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sanjay Asthana · 2019 to 2026
$34.5M
The Longitudinal Course of Neural Function and Amyloid in People At Risk for ADR01AG021155 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sterling C Johnson · 2004 to 2026
$27.0M
Wisconsin Registry for Alzheimer's PreventionRF1AG027161 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI JOHNSON, STERLING C · 2018 to 2018
$18.8M
Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-ADU01AG061359 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KASTENMULLER, GABI · 2018 to 2022
$10.0M
Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer-type DementiasRF1AG051550 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KLING, MITCHEL ALLAN · 2015 to 2016
$6.3M
Metabolic Networks and Pathways Predictive of Sex Differences in AD Risk and Responsiveness to TreatmentRF1AG059093 · NIA · DUKE UNIVERSITY · PI BRINTON, ROBERTA EILEEN, CHANG, RUI · 2018 to 2018
$5.9M
White matter degeneration: biomarkers in preclinical Alzheimer's DiseaseR01AG037639 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BENDLIN, BARBARA BRIGITTA · 2012 to 2023
$5.3M
Metabolic Networks and Pathways in Alzheimer's DiseaseR01AG046171 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F · 2014 to 2017
$4.4M
Gut barrier function in Alzheimer's DiseaseR01AG070973 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BENDLIN, BARBARA BRIGITTA, REY, FEDERICO E · 2021 to 2025
$3.9M
TargetAD: A systems multi-omics approach to drug repositioning in Alzheimer's diseaseR01AG069901 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI Matthias Arnold, Jan Krumsiek · 2021 to 2026
$3.7M
Genomic and Metabolomic Data Integration in a Longitudinal Cohort at Risk for Alzheimer's DiseaseR01AG054047 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI ENGELMAN, CORINNE D. · 2016 to 2020
$3.6M
NIA NIH HHS P30 AG062715NIA NIH HHS R01 AG021155NIA NIH HHS R01 AG037639NIA NIH HHS R01 AG046171NIA NIH HHS R01 AG054047NIA NIH HHS R01 AG069901NIA NIH HHS R01 AG070973NIA NIH HHS RF1 AG027161NIA NIH HHS RF1 AG051550NIA NIH HHS RF1 AG057452NIA NIH HHS RF1 AG058942NIA NIH HHS RF1 AG059093NIA NIH HHS U01 AG061359NIA NIH HHS U19 AG063744NIGMS NIH HHS T32 GM081061NINDS NIH HHS F99 NS130922
6 · The paper itself

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. 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.

Indexed as

Alzheimer DiseaseGastrointestinal MicrobiomeMicrobiotaFormatesGenomicsHumansFormatesAlzheimer’s diseaseCo-metabolismConstraint-based modellingFormateHost-microbiomeMetabolic modellingMetabolomicsMicrobiomePathways

Identifiers

PMID38480804
PMCPMC10937638
OpenAlexW4392761546

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.