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

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

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 fo...

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Main 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
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Scientific Reports
Subjects:
Alzheimer’s disease
Metabolic modelling
Constraint-based modelling
Microbiome
Formate
Metabolomics
Online Access:https://doi.org/10.1038/s41598-024-55960-3
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Summary: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 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. We predicted microbial formate as well as other microbial metabolites, which could alter urine formate production in the host-microbiome personalised 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.
ISSN:2045-2322

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