Evidence map›Paper›PMID 37720019›Full record

ArticleResearch square2023

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

Filippo Martinelli, Almut Heinken, Ann-Kristin Henning, Maria A Wörheide, Tim Hensen, Antonio González, Matthias Arnold, Sanjay Asthana, Kathrin Budde, Corinne D Engelman and 30 more

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

40 authors at 14 institutions in 4 countries.

Filippo MartinelliUniversity of Galway.
Almut HeinkenUniversity of Lorraine.
Ann-Kristin HenningUniversity Medicine Greifswald.
Maria A WörheideHelmholtz Zentrum München - German Research Center for Environmental Health.
Tim HensenUniversity of Galway.
Antonio GonzálezUniversity of California San Diego.
Matthias ArnoldHelmholtz Zentrum München - German Research Center for Environmental Health.
Sanjay AsthanaUniversity of Wisconsin-Madison.
Kathrin BuddeUniversity Medicine Greifswald.
Corinne D EngelmanUniversity of Wisconsin-Madison.
Mehrbod EstakiUniversity of California San Diego.
Hans-Jörgen GrabeUniversity Medicine Greifswald.
Margo HestonUniversity of Wisconsin-Madison.
Sterling JohnsonUniversity of Wisconsin-Madison.
Gabi KastenmüllerHelmholtz Zentrum München - German Research Center for Environmental Health.
Cameron MartinoUniversity of California San Diego.
Daniel McDonaldUniversity of California San Diego.
Federico ReyUniversity of Wisconsin-Madison.
Ingo KilimannUniversity Medicine Rostock.
Olive PetersCharité-Universitätsmedizin Berlin.
Xiao WangCharité-Universitätsmedizin Berlin.
Eike Jakob SpruthCharité-Universitätsmedizin Berlin.
Anja SchneiderUniversity of Bonn.
Klaus FliessbachUniversity of Bonn.
Jens WiltfangUniversity of Goettingen.
Niels HansenUniversity of Goettingen.
Wenzel GlanzGerman Center for Neurodegenerative Diseases.
Katharina BuergerUniversity Hospital, LMU Munich.
Daniel JanowitzUniversity Hospital, LMU Munich.
Christoph LaskeUniversity of Tübingen.
Matthias H MunkUniversity of Tübingen.
Annika SpottkeUniversity of Bonn.
Nina RoyGerman Center for Neurodegenerative Diseases.
Matthias NauckUniversity Medicine Greifswald.
Stefan TeipelUniversity Medicine Rostock.
Rob KnightUniversity of California San Diego.
Rima Kaddurah-DaoukDuke University.
Barbara B BendlinUniversity of Wisconsin-Madison.
Johannes HertelUniversity Medicine Greifswald.
Ines ThieleUniversity of Galway.
University of Wisconsin–Madison · USUniversitätsmedizin Greifswald · DEUniversity of California San Diego · USCenter for Environmental Health · USCharité - Universitätsmedizin Berlin · DEOllscoil na Gaillimhe – University of Galway · IEUniversity of Bonn · DEGerman Center for Neurodegenerative Diseases · DELMU Klinikum · DEUniversity of Göttingen · DEUniversity of Rostock · DEUniversity of Tübingen · DEDuke University · USUniversité de Lorraine · FR

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
Genomic and Metabolomic Data Integration in a Longitudinal Cohort at Risk for Alzheimer's DiseaseRF1AG054047 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI ENGELMAN, CORINNE D. · 2022 to 2025
$3.8M
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
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 AG054047NIA 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 utilized 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 personalized 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’s diseaseco-metabolismconstraint-based modellingformatehost-microbiomemetabolic modellingmetabolomicsmicrobiomepathways

Identifiers

PMID37720019
PMCPMC10503865
OpenAlexW4386448990

What OpenQuestion holds

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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 OpenQuestion graph.