The microbiome is associated with obesity-related metabolome signature in the process of aging.

Aging involves changes in the gut microbiome impacting health and longevity; however, the roles of specific microbial metabolites remain understudied. Here, we examine the microbial contribution to the metabolic profile in aged mice. Fecal samples were collected from female Swiss-Webster mice raised conventionally (Conv) or germ free (GF), at 8 weeks (young) and 18 (aged) months of age, and the microbiome and metabolome were characterized. Significant differences were observed in bacterial composition and its predicted functional activity between young and aged mice. Interestingly, we found more age-related differences in metabolite abundances among Conv mice than GF mice, highlighting the contribution of the microbiome to aging. Moreover, microbiome-associated metabolites, predominantly lipids, were higher in aged mice, with linoleic acid metabolism enriched in this group. Our study underscores a microbiome-dependent component to age-related metabolic changes in mice, particularly in lipid-associated pathways, and contributes to the growing body of literature linking gut microbiota to host metabolism in aging.