Longitudinal analyses reveal that aging-related alterations in the intestinal environment promote HFD-induced obesity

Abstract Background: Aging is a progressive decline of cellular functions that ultimately affects whole-body homeostasis. Alterations in the gut microbiota associated with aging have been reported, however, these studies were mainly based on the simple comparison of young and old subjects. In this study, we longitudinally analyzed fecal microbial community composition, together with fecal and plasma metabolomes, in C57BL/6J mice over a period of 72 weeks. Result: By using longitudinal microbiome and metabolome analyses, we found aging-related alterations in fecal microbiota and metabolome profiles. There was a significant reduction in gut microbial diversity with ageand, in addition, the fecal metabolome showed a significant decrease in monosaccharides and an increase in the metabolites of energy metabolism. In the age-related change of plasma metabolites, amino acids were significantly increased. The features of age-related changes in the fecal bacteria and metabolites were consistent with those observed in obesity and diabetes studies. Consistently, fecal microbiota transplantation from agedspecific pathogen-free (SPF) mice into young germ-free (GF) mice resulted in increased weight gain and impaired glucose tolerance. Conclusion: Our findings provide new insights into the relationships between host aging and gut environmental changes and may contribute to the development of a solution to aging-related diseases such as obesity.