Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes

Abstract

AbstractWhile rapid demographic changes in Asia are driving the incidence of chronic diseases related to aging, the limited availability of high-qualityin vivodata hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging the availability of a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun metagenomic sequencing to do high-resolution taxonomic and functional characterization of their gut microbiomes (n=234). Joint species-level analysis with other Asian cohorts identified a distinct age-associated shift in Asian gut metagenomes, characterized by a reduction in microbial richness, and enrichment of specificAlistipesandBacteroidesspecies (e.g.Alistipes shahiiandBacteroides xylanisolvens). Functional pathway analysis confirmed that these changes correspond to a metabolic potential expansion in aging towards alternate pathways that synthesize and utilize amino-acid precursors, relative to the dominant microbial guilds that typically produce butyrate in the gut from pyruvate (e.g.Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust gut microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species such asParabacteroides goldsteiniiand pathobionts such asKlebsiella pneumoniae, highlighting the role of the microbiome as biomarkers and potential intervention targets for promoting healthy aging.