Age-related microbiome metabolites alter RNA splicing and chromatin accessibility in the brain.

ABSTRACT: The gut microbiome generates diverse metabolites that can enter the bloodstream and alter host biology, including brain function. Hundreds of physiologically relevant, gut-brain signaling molecules likely exist; however, there has been no systematic, high-throughput effort to identify and validate them. Here, we integrate computational, in vitro, and in vivo approaches to pinpoint microbiome-derived metabolites whose blood levels change during aging, and that induce corresponding changes in the mouse brain. First, we mine large-scale metabolomics datasets from human cohorts (each n ≥ 1200) to identify 30 microbiome-associated metabolites whose blood levels change with age. We then screen this panel in an in vitro transcriptomic assay to identify metabolites that

SUBMITTER: Chakraborty M 

PROVIDER: S-EPMC12621679 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature