Influence of age on intestinal bile acid transport in C57BL/6 mice

Abstract

Intestinal and hepatic bile acid transporters are important for enterohepatic bile acid circulation and pharmacokinetics. Based on previous literature, we hypothesized that the expression of bile acid transporters and intestinal bile acid absorption are lower in older individuals. Here, we measured active taurocholate absorption across the ileum of male C57BL/6 mice in two different age cohorts – young (age range of 89–224 days) and old (age range of 613–953 days). Also examined in these mice were mRNA expression of the major bile acid transporters – Asbt and Ostα/β in the ileum, and Ntcp, Oatp1b2 and Bsep in the liver. Mean intestinal taurocholate absorption was significantly lower (~50%) in mice in the older cohort compared to those in the younger cohort. In the ileum, the expression of Asbt was significantly lower in the older cohort, but expression of Ostα/β was not affected by age. The lower capacity for intestinal bile acid absorption in the older animals is consistent with their lower expression level of Asbt. Of the hepatic bile acid transporters examined, expression of Ntcp and Oatp1b2 were significantly lower in the older mice. This is the first study to directly measure intestinal bile acid absorption as a function of age. The data suggest a lower capacity for intestinal bile acid absorption in older animals. Also, lower expression of Asbt, Ntcp, and Oatp1b2 in older individuals could influence pharmacokinetics of drug substrates.

Effects of dietary pectin on the profile and transport of intestinal bile acids in young pigs

“…Alteration in intestinal BA transport is closely related to expressional changes in BA transporters. Gao et al (2017) showed that aged mice have less ASBT and taurocholate transport in the ileum. Zhu et al (2017a) found consumption of modified pectin downregulate FABP6 and OSTα/β to inhibit absorption of BAs in the ileum.…”

The Roles of Lipid Metabolism in the Pathogenesis of Chronic Diseases in the Elderly

“…As was consistent with human studies, the reabsorption of BA in the ileum of aging mice was similarly reduced, with about a 50% lower absorption of taurocholate than in younger mice. This was supported by the reduced gene expression of apical sodiumdependent bile acid transporter (Asbt), which is the key transporter regulating BA uptake in the intestinal apical membrane [27]. These observations suggest that the decreased expression of Asbt potentially acts as a rate-determining step in BA reabsorption.…”

“…The age-related decreases in BA synthesis and their potential impact on cholesterol utilization are closely linked to the observed disturbances in the enterohepatic circulation of BAs during aging, which are evidenced by the reduced intestinal reabsorption and liver transport of the BAs. Aging was associated with the decreased mRNA expression of the intestinal BAs reabsorption transporter Asbt [27]. The mRNA expressions of the liver BA uptake transporters Na+/taurocholate cotransporting polypeptide (Ntcp) and organic anion transporting polypeptide 1b2 (Oatp1b2) were decreased during aging, whereas the expression of the BAs efflux transporter Bsep remained unchanged in aging mice [27,89].…”

Intestinal Absorption of Bile Acids in Health and Disease

“…While it is clear that ASBT expression is enhanced after weaning, there is also evidence that aging decreases intestinal bile acid absorption. Studies by Gao et al demonstrated that 3 H-TC uptake across ileum in Ussing chambers was reduced approximately 50% in a cohort of aged ~2-year-old) C57BL/6 mice relative to a younger (<1-year-old) cohort (133). There was a corresponding approximately 50% decrease in ASBT mRNA expression in the older cohort, suggesting that decreased ASBT expression in old age may be responsible for the reduced bile acid absorption in these mice.…”