Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease
Year: 2024
Type: article
Study design: Observational Study
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.
Source: Scientific Reports
Authors: Filippo Martinelli, Almut Heinken, Ann-Kristin Henning, Maria A. Ulmer, Tim Hensen, Antonio González, Matthias Arnold, Sanjay Asthana, Kathrin Budde, Corinne D. Engelman, Mehrbod Estaki, Hans-Jörgen Grabe, Margo B. Heston, Sterling Johnson, Gabi Kastenmüller, Cameron Martino, Daniel McDonald, Federico E. Rey, Ingo Kilimann, Olive Peters, Xiao Wang, Eike Jakob Spruth, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Niels Hansen, Wenzel Glanz, Katharina Buerger, Daniel Janowitz, Christoph Laske, Matthias H. Munk, Annika Spottke, Nina Roy, Matthias Nauck, Stefan Teipel, Rob Knight, Rima F. Kaddurah-Daouk, Barbara B. Bendlin, Johannes Hertel, Ines Thiele
Institutions: Ollscoil na Gaillimhe – University of Galway, Inserm, Nutrition-Génétique et Exposition aux Risques Environnementaux, Université de Lorraine, Universitätsmedizin Greifswald, Helmholtz Munich, Institute of Computational Biology, University of California San Diego, Duke University, University of Wisconsin–Madison, University of Wisconsin Health, German Center for Neurodegenerative Diseases, Universitätsmedizin Rostock, Charité – Universitätsmedizin Berlin, Stiftung Charité, University of Bonn, University of Aveiro, University of Göttingen, Institut für Schlaganfall- und Demenzforschung, Ludwig-Maximilians-Universität München, Hertie Institute for Clinical Brain Research, University of Tübingen, German Centre for Cardiovascular Research, Duke Medical Center, APC Microbiome Institute
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,590
Awards: Metabolic Networks and Pathways Predictive of Sex Differences in AD Risk and Responsiveness to Treatment, G160596578, Metabolic Network Analysis of Biochemical Trajectories in Alzheimer's Disease, Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine, Gut Liver Brain Biochemical Axis in Alzheimer's Disease, Alzheimer's Gut Microbiome Project, G420208702, G434337789, Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer-type Dementias, Wisconsin Registry for Alzheimer's Prevention, White matter degeneration: biomarkers in preclinical Alzheimer's Disease, G5098725405, APC_Phase 2, Genomic and Metabolomic Data Integration in a Longitudinal Cohort at Risk for Alzheimer's Disease, Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-AD, The Disadvantage Exposome as a Driver of Alzheimer’s Disease Pathology, G6597655368, TargetAD: A systems multi-omics approach to drug repositioning in Alzheimer's disease, G6928989159, Graduate Training In Cellular And Molecular Pathogenesis Of Human Diseases, Metabolic Networks and Pathways in Alzheimer's Disease, Genomic and Metabolomic Data Integration in a Longitudinal Cohort at Risk for Alzheimer's Disease, The Longitudinal Course of Imaging Biomarkers in People At Risk for Alzheimer’s Disease, Gut barrier function in Alzheimer’s disease, Wisconsin Alzheimer's Disease Research Center
OpenAlex ID: W4392761546