Altered Bile Acid Metabolism is Related to Gut Microbiome Aging
Researchers here discuss a bidirectional relationship between age-related alterations in bile acid metabolism, centered in the liver, and changes in the composition of the gut microbiome. These changes take place in the context of increasing dsyfunction of the intestinal barrier with age, allowing unwanted bacteria and bacterial metabolites into the body to provoke chronic inflammation and other dysfunction. Researchers have demonstrated in animal studies that restoration of a youthful gut microbiome composition can improve health and extend life; an interesting question is the degree to which restoration of a youthful bile acid metabolism can achieve similar outcomes.
Bile acids (BAs), byproducts of cholesterol metabolism in the liver, are not only vital for lipid digestion and absorption of lipid-soluble vitamins but also act as signaling molecules influencing aging, inflammation control, immune homeostasis, and tumor development. They regulate gut microbiota growth and composition, while gut microbiota significantly influence BA hydrolysis and the synthesis of secondary and tertiary BAs. This interplay affects immune function and metabolic phenotypes, and may contribute to obesity, diabetes, non-alcoholic fatty liver disease, inflammatory bowel disease, and certain cancers.
100 elderly and 100 young participants were enrolled in this study. Fecal and serum BAs were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), while gut microbiota composition was assessed through 16S rRNA gene sequencing. Elderly participants exhibited significantly lower levels of primary fecal BAs, particularly cholic acid (CA) and chenodeoxycholic acid (CDCA), alongside an increase in secondary BAs such as lithocholic acid (LCA), leading to a marked reduction in the primary/secondary BAs ratio.
Serum showed a decline in both conjugated and unconjugated BAs, primary/secondary BAs ratio, while a notable rise in 12α-OH/non-12α-OH BAs. Furthermore, increased levels of P21, LPS, IL-6, and TNF-α in the elderly were associated with specific BA changes, including reduced fecal unconjugated primary BAs and increased LCA. Significant differences in gut microbiota composition were observed, with the elderly displaying a higher abundance of microbiota capable of 7α-dehydroxylation. Correlations were observed among BAs, gut microbiota alterations, and markers of chronic inflammation and intestinal barrier dysfunction.
In conclusion, aging is associated with significant changes in the BA pool, which are associated with gut microbiota dysbiosis. These alterations may be related to intestinal barrier dysfunction and chronic low-grade inflammation. Modulating BA metabolism presents a potential strategy for mitigating the aging process.