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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)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords 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

Journal Scientific Reports

Quellenangaben Volume: 14, Issue: 1, Article Number: 6095

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)

Grants 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