Gut Microbiota-Regulated Bile Acids Metabolism Features In The Aging Process In Mice

Aging is usually characterized with imbalanced gut microbiota and bile acids (BAs) dyshomeostasis. However, the gut microbiota-regulated BA metabolism features in the aging process remains unclear. To establish a direct link between gut microbiota and BA profile changes in the liver, plasma and intestinal contents. UPLC-MS/MS, 16S rDNA sequencing, Western blotting, and HE staining methods were used. The plasma content of TC, TG and LDL-C gradually increased during aging, the Lactobacillus , Bacteroides , Bacillus , Ruminococcus , Blautia and Streptococcus which can produce BSH were increased. The concentration of total BAs was increased, especially unconjugated BAs, and the ratio of unconjugated BAs to conjugated BAs was increased. The expression of bile acid transporter receptors and intestinal tight junction proteins were significantly decreased. The presented data revealed that the changes of BA profile mediated by gut microbiota were closely related to aging, and highlights that prevention and treatment of aging-related disorders, especially disorders of lipid metabolism by targeting gut microbiota-regulated BAs metabolism should be payed more attention. In the current study, we established a direct link between gut microbiota and BA profile changes in the liver, plasma, and intestinal contents, and detected protein expression of bile acid transporter receptors bile salt export pump (BSEP), apical sodium-dependent bile acid transporter (ASBT), multidrug resistance-associated protein 2(MRP2) and intestinal tight junction proteins zonula occludens-1 (ZO-1), Occludin and Claudin-5 during aging. The content of TC, TG and LDL-C in plasma gradually increased during aging, the Lactobacillus , Bacteroides , Bacillus , Ruminococcus , Blautia, and Streptococcus which can produce bacterial enzymes bile salt hydrolase (BSH) were increased. The concentration of total BAs in intestinal contents and plasma was increased, especially the content of unconjugated BAs, and the ratio of unconjugated BAs to conjugated BAs was increased in liver, plasma and intestinal contents. The expression of BSEP and MRP2 in the liver and ASBT in the intestinal were significantly decreased. Meanwhile, the expression of ZO-1, Occludin, and Claudin-5 were decreased. The presented data reveals that the changes of BA profile mediated by gut microbiota was closely related to aging, and highlights that the prevention and treatment of aging-related disorders, especially disorders of lipid metabolism by targeting gut microbiota-regulated BAs metabolism would become a promising therapy for the prevention and treatment of aging.