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Martinelli, F.* ; Heinken, A.* ; Henning, A.K.* ; Ulmer, M.A. ; Hensen, T.* ; González, A.* ; Arnold, M. ; Asthana, S.* ; Budde, K.* ; Engelman, C.D.* ; Estaki, M.* ; Grabe, H.J.* ; Heston, M.B.* ; Johnson, S.* ; Kastenmüller, G. ; Martino, C.* ; McDonald, D.* ; Rey, F.E.* ; Kilimann, I.* ; Peters, O.* ; Wang, X.* ; Spruth, E.J.* ; Schneider, A.* ; Fliessbach, K.* ; Wiltfang, J.* ; Hansen, N.* ; Glanz, W.* ; Buerger, K.* ; Janowitz, D.* ; Laske, C.* ; Munk, M.H.* ; Spottke, A.* ; Roy, N.* ; Nauck, M.* ; Teipel, S.* ; Knight, R.* ; Kaddurah-Daouk, R.F.* ; Bendlin, B.B.* ; Hertel, J.* ; Thiele, I.*

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

Sci. Rep. 14:6095 (2024)
Verlagsversion DOI PMC
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Alzheimer’s Disease ; Co-metabolism ; Constraint-based Modelling ; Formate ; Host-microbiome ; Metabolic Modelling ; Metabolomics ; Microbiome ; Pathways; Association Workgroups; Diagnostic Guidelines; National Institute; Recommendations; Onset
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 14, Heft: 1, Seiten: , Artikelnummer: 6095 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen National Institute of Neurological Disorders And Stroke
Science Foundation Ireland
European Research Council (ERC) under the European Union
NIA
FNIH
National Institute of General Medical Sciences
National Institute on Aging
Wisconsin studies includes a Wisconsin Partnership Program grant