Whole-body modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease
Author:
Martinelli Filippo1, Heinken Almut2, Henning Ann-Kristin3, Wörheide Maria A.4, Hensen Tim1, González Antonio5, Arnold Matthias4, Asthana Sanjay6, Budde Kathrin3, Engelman Corinne D.6, Estaki Mehrbod5, Grabe Hans-Jörgen3, Heston Margo6, Johnson Sterling6, Kastenmüller Gabi4, Martino Cameron5, McDonald Daniel5, Rey Federico6, Kilimann Ingo7, Peters Olive8, Wang Xiao8, Spruth Eike Jakob8, Schneider Anja9, Fliessbach Klaus9, Wiltfang Jens10, Hansen Niels10, Glanz Wenzel11, Buerger Katharina12, Janowitz Daniel12, Laske Christoph13, Munk Matthias H.13, Spottke Annika9, Roy Nina11, Nauck Matthias3, Teipel Stefan7, Knight Rob5, Kaddurah-Daouk Rima14, Bendlin Barbara B.6, Hertel Johannes3, Thiele Ines1
Affiliation:
1. University of Galway 2. University of Lorraine 3. University Medicine Greifswald 4. Helmholtz Zentrum München – German Research Center for Environmental Health 5. University of California San Diego 6. University of Wisconsin-Madison 7. University Medicine Rostock 8. Charité-Universitätsmedizin Berlin 9. University of Bonn 10. University of Goettingen 11. German Center for Neurodegenerative Diseases 12. University Hospital, LMU Munich 13. University of Tübingen 14. Duke University
Abstract
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.
Publisher
Research Square Platform LLC
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