Integrative multiomics analysis reveals host-microbe-metabolite interplays associated with the aging process in Singaporeans.

The age-associated alterations in microbiomes vary across populations due to the influence of genetics and lifestyles. To the best of our knowledge, the microbial changes associated with aging have not yet been investigated in Singapore adults. We conducted shotgun metagenomic sequencing of fecal and saliva samples, as well as fecal metabolomics to characterize the gut and oral microbial communities of 62 healthy adult male Singaporeans, including 32 young subjects (age, 23.1 ± 1.4 years) and 30 elderly subjects (age, 69.0 ± 3.5 years). We identified 8 gut and 13 oral species that were differentially abundant in elderly compared to young subjects. By combining the gut and oral microbiomes, 25 age-associated oral-gut species connections were identified. Moreover, oral bacteria Acidaminococcus intestine and Flavonifractor plautii were less prevalent/abundant in elderly gut samples than in young gut samples, whereas Collinsella aerofaciens and Roseburia hominis showed the opposite trends. These results indicate the varied gut-oral communications with aging. Subsequently, we expanded the association studies on microbiome, metabolome and host phenotypic parameters. In particular, Eubacterium eligens increased in elderly compared to young subjects, and was positively correlated with triglycerides, which implies that the potential role of E. eligens in lipid metabolism is altered during the aging process. Our results demonstrated aging-associated changes in the gut and oral microbiomes, as well as the connections between metabolites and host-microbe interactions, thereby deepening the understanding of alterations in the human microbiome during the aging process in a Singapore population.

Comparative Blood and Urine Metabolomics Analysis of Healthy Elderly and Young Male Singaporeans.

Comparative metabolomics analysis of biofluids could provide information about the metabolic alterations in aging. To investigate the signature of multiple metabolic profiles associated with aging in an Asian population, we performed a pilot study in healthy Singaporeans, including 33 elderly and 33 young males. Fasting whole bloods were analyzed by routine hematology; the serum and urine metabolome profiles were obtained using NMR-based nontargeted metabolomics analysis and targeted lipoprotein analysis. Among the 90 identified compounds in serum and urine samples, 32 were significantly different between the two groups. The most obvious age-related metabolic signatures include decreased serum levels of albumin lysyl and essential amino acids and derivatives but increased levels of N-acetyl glycoproteins and several lipids and elevated urine levels of trimethylamine N-oxide, scyllo-inositol, citrate, and ascorbic acid but decreased levels of several amino acids, acetate, etc. Among 112 lipoprotein subfractions, 65 were elevated, and 2 were lower in the elderly group. These significantly age-varying metabolites, especially in the amino acid and fatty acid metabolism pathways, suggest that the regulation of these pathways contributes to the aging process in Chinese Singaporeans. Further multiomics studies including the gut microbiome and intervention studies in a larger cohort are needed to elucidate the possible mechanisms in the aging process.