Age-dependent remodeling of gut microbiome and host serum metabolome in mice

Abstract

The interplay between microbiota and host metabolism plays an important role in health. Here, we examined the relationship between age, gut microbiome and host serum metabolites in male C57BL/6J mice. Fecal microbiome analysis of 3, 6, 18, and 28 months (M) old mice showed that the Firmicutes / Bacteroidetes ratio was highest in the 6M group; the decrease of Firmicutes in the older age groups suggests a reduced capacity of gut microflora to harvest energy from food. We found age-dependent increase in Proteobacteria , which may lead to altered mucus structure more susceptible to bacteria penetration and ultimately increased intestinal inflammation. Metabolomic profiling of polar serum metabolites at fed state in 3, 12, 18 and 28M mice revealed age-associated changes in metabolic cascades involved in tryptophan, purine, amino acids, and nicotinamide metabolism. Correlation analyses showed that nicotinamide decreased with age, while allantoin and guanosine, metabolites in purine metabolism, increased with age. Notably, tryptophan and its microbially derived compounds indole and indole-3-lactic acid significantly decreased with age, while kynurenine increased with age. Together, these results suggest a significant interplay between bacterial and host metabolism, and gut dysbiosis and altered microbial metabolism contribute to aging.

Gut Microbiota Predicts Healthy Late-Life Aging in Male Mice

“…In this study, we examined the gut microbiota collected at 21 and 30 months of age from 22 mice and measured the aging status. Concordant with previous reports, we found that aging was associated with increased alpha diversity [ 64 ], but in our dataset this pattern was driven by the observation of higher alpha diversity in the healthy aging cohort. Consistent with previous work [ 65 ], our study also linked aging to an increase in interindividual variation in gut microbial community composition, with interindividual variation being especially high in the normal aging group.…”

“…Although several previous studies demonstrated the links between gut microbiota and aging in mice, these studies mainly focused on the comparison between different growth stages [ 62 , 63 , 64 ]. In this study, we examined the gut microbiota collected at 21 and 30 months of age from 22 mice and measured the aging status.…”

Gut Microbiota predicts Healthy Late-life Aging in Male Mice

“…In this study, we examined the gut microbiota collected at 21 and 30 months of age from 22 mice and measured the aging status. Concordant with previous reports, we found that aging was associated with increased alpha diversity 67 . In particular, only healthy aging mice showed significantly increased Shannon diversity with age.…”

“…Although several previous studies demonstrated the links between gut microbiota and aging in mice, these studies mainly focused on the comparison between different growth stages [65][66][67] . In this study, we examined the gut microbiota collected at 21 and 30 months of age from 22 mice and measured the aging status.…”

Gut Microbiome and Cellular Senescence in the Context of Aging and Disease: An Emerging Frontier

“…Illustration created at app.biorender.com. However, studies delineating the role of gut metabolome alterations with lifespan and diseases are limited, and are only beginning to be understood (Wu et al, 2021;Zhang et al, 2021). Since, there is evidence that secretory metabolites of commensal bacteria can directly modulate SC development (Kumar et al, 2020), it would be interesting to assess how agedependent gut metabolome changes affect the oxi-inflammatory stress in the gut, and whether these changes could be correlated with increased SC burden in the intestine (Figure 4).…”