Gut Microbiota Affects Age-Related Plasma Metabolites

Older age is a well-established risk factor for many chronic diseases, yet the biological mechanisms underlying this increased risk are not fully understood. Both gut microbiome composition and the plasma metabolome change with age and may help explain how aging influences disease susceptibility. In this study, we examined the associations between age-related gut microbiota and metabolomic biomarkers in participants of the Baltimore Longitudinal Study of Aging (BLSA), covering a broad age range (27-98 years; 55% female). At the phylum level, we identified four age-associated phyla: Firmicutes, which was negatively associated with age, and Proteobacteria, Euryarchaeota, and Verrucomicrobia, which were positively associated with age. At the genus level, six genera-<i>Akkermansia</i>, <i>Escherichia</i>, <i>Klebsiella</i>, <i>Methanobrevibacter</i>, <i>Oscillibacter,</i> and <i>Ruthenibacterium</i>-were positively associated with age, whereas <i>Faecalibacterium</i> and <i>Longibaculum</i> were negatively associated with age. Many of these microbial taxa were found to influence one or more aging-related metabolites, mediating their effects across various metabolite classes, including bile acids, amino acids, triglycerides, cholesteryl esters, and phosphatidylcholines. Notably, three metabolites, Asparagine, Sphingomyelin C26:0, and Dihydroceramide (d18:0/24:1), were associated with a decreased risk of mortality, whereas six metabolites-Glycoursodeoxycholic acid, Triacylglyceride (16:1_34:3), Triacylglyceride (18:0_34:3), Phosphatidylcholine aa C32:1, Phosphatidylcholine aa C32:2, and Cholesteryl ester 16:1-were linked to an increased risk of mortality. This study highlights connections between age-associated gut microbial taxa at both the phylum and genus levels as potential mediators of circulating metabolites that are linked to mortality risk.