Characterizing functions of endogenous bile acid pools altered by Asbt-deficiency in the ileal transcriptional regulation.
Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B194
Abstract ID: 6062
Presenting Author:
Koichi Sudo , Research Postdoctoral Fellow, Gastro Research at Dartmouth Hlth.
Abstract:
Bile acids (BAs) are a diverse and abundant class of metabolites synthesized in the liver, absorbed in the ileum, and metabolized by the colonic microbiota. Besides the classical functions of BAs for lipid and vitamin absorptions in the small intestine (SI), BAs have emerged as potent immunoregulatory metabolites via interactions with G protein-coupled and nuclear receptors (NRs; e.g., FXR/NR1H4). Alterations of BA metabolism have been reported in human diseases, e.g., inflammatory bowel diseases. However, it remains unclear whether or how altered BA pools may influence the intestinal homeostasis and pathology. As in vivo studies cannot uncouple the regulatory functions of BAs from their impact on microbiota, I have developed a novel intestinal explant culture system, in which the ileal fragments can be treated with the endogenous BA pools from normal or diseased mice. The ileal, not colonic, fragments induced mRNA expressions of BA-targeted genes in the presence of (t)CDCA which is a representative and FXR-agonistic BA. Then, the fragments were cultured with the endogenous SI BA pools from healthy or Asbt-/- mice – which have altered BA pools. RNA-seq showed that some genes were similarly induced, but others were differentially regulated by each BA pools. In NR reporter assays, the BA pools from Asbt-/- mice potently activated RXRa, PXR, and ERb. Together, this study suggests abnormal BA pools differentially modulate the ileal environment via distinct NR pathways.
Characterizing functions of endogenous bile acid pools altered by Asbt-deficiency in the ileal transcriptional regulation.
Category
Poster and Podium (Block Symposium)