Changes in the Gut Microbiome Correlate with Aging and Renal Function

The gut microbiome changes with age. Pro-inflammatory microbial populations grow in size at the expense of populations that produce beneficial metabolites. As researchers produce increasingly large databases of the composition of the gut microbiome across ages and populations, they are also mapping a growing number of specific connections between microbial species and aspects of aging. Some of this work shows causation, but most human data can only show correlations between aspects of the gut microbiome and aspects of aging.

In today's open access paper, the authors focused on finding links between the gut microbiome and the function of the kidney. Declining kidney function is clearly important in degenerative aging, affecting organs throughout the body. If changes in the gut microbiome can accelerate kidney aging, then this will contribute to aging in much of the rest of the body as well.

Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging

Several cross-sectional studies have identified gut microbiota changes that occur with aging. Studies using 16S rRNA gene amplicon sequencing have indicated an association between diet-driven microbiota alterations and health decline in aging individuals and highlighted the presence of a core microbiota of prevalent, symbiotic bacterial taxa dominated by the families Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae, with a progressive reduction in the abundance of these core taxa with age. In recent years, deep shotgun sequencing studies have reported a trend toward an increase in the abundances of Escherichia and Streptococcus with age, while the abundances of Faecalibacterium and Ruminococcus were reported to exhibit a decreasing trend. Notably, compared to that in other age groups, the gut microbiota of healthy centenarians is enriched with bacteria with a potential for degradation of xenobiotics and biosynthesis of short-chain fatty acids. However, whether specific interactions between the serum metabolome and gut microbiota are related to an age-dependent decline in renal function remains largely unexplored.

Based on residents from a Chinese longevity county, with long-living individuals (nonagenarians and centenarians) as healthy aging controls, this study aimed to examine the possible relationship between renal function and age-associated alterations in the human gut microbiota and serum metabolome using an integrated omics approach. Our results indicated that the effect of the gut microbiota on serum metabolites increased with age and that many age-associated gut microbes (E. coli, O. splanchnicus, and D. piger in particular) and serum metabolites, including markers of impaired renal function and bile acids, were highly correlated. The relationships between renal functions, serum metabolites, and the gut microbiota further indicated a possible impact of the gut microbiota in the aging process. Through mediation analyses, we revealed putative causal relationships among the gut microbiota (E. coli, O. splanchnicus, and D. piger), markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and age.

Separately, feces of elderly individuals were transplanted into C57BL/6J mice. This fecal microbiota transplantation (FMT) experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Thus, this study not only revealed changes in the serum metabolome and the gut microbiota in the process of aging but also indicated a route by which the gut microbiota affects aging indirectly through its effect on renal function via the production of metabolites associated with impaired renal function.