The microbiome affects obesity-related metabolites in the process of aging

Introduction: Aging involves changes in the gut microbiome that impact health and longevity, however which microbial metabolites play a role remain understudied. Here we examine the contribution of the microbiome to the metabolic profile in aged mice. Methods: Fecal samples were collected from 8 weeks-old (young) and 18 months-old (aged) Swiss-Webster mice raised conventionally (Conv) or germ free (GF). Bacterial DNA from fecal samples were sequenced and microbiome analysis was done using QIIME2. Liquid chromatography mass spectrometry was used for untargeted metabolomics on Conv and GF samples. Results: Significant differences were observed in bacterial composition and predicted functional pathways between young and aged mice. Age-related metabolome variance was greater in Conv compared to GF mice, highlighting the microbial contribution to metabolic changes. Moreover, microbiome-associated metabolites, predominantly lipids, were higher in aged mice compared to young mice, with the linoleic acid metabolism pathway being enriched in the aged group. Conclusions: These findings underscore the intricate relationship between aging, the gut microbiome, and metabolic changes. The observed age-related shifts in bacterial composition and metabolites, coupled with the enrichment of microbiome-associated lipids in aged mice, emphasize the potential role of the gut microbiome in modulating metabolic health during aging.