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

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.

Déclaration de conflit d'intérêts

Declaration of interests GK and MA are co-inventors of several patent applications on the use of metabolomics in Alzheimer’s disease and own equity and IP in Chymia LLC and IP in PsyProtix unrelated to this work. RKD is an inventor of a series of patents on the use of metabolomics for the diagnosis and treatment of CNS diseases and holds equity in Metabolon Inc., Chymia LLC and PsyProtix. ST has served on national and international advisory boards of Roche, Eisai, Grifols, and Biogen, and is a member of the independent data safety and monitoring board of the study ENVISION (Biogen). HJG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care.