Taurocholate uptake by Caco-2 cells is inhibited by pro-inflammatory cytokines and butyrate.

Inflammatory bowel disease (IBD) is a group of chronic and life-threating inflammatory diseases of the gastrointestinal tract. The active intestinal absorption of bile salts is reduced in IBD, resulting in higher luminal concentrations of these agents that contribute to the pathophysiology of IBD-associated diarrhea. Butyrate (BT) is a short-chain fatty acid produced by colonic bacterial fermentation of dietary fibers. BT utilization is impaired in the intestinal inflamed mucosa of IBD patients. Our aim was to investigate the link between IBD and bile acid absorption, by testing the effect of the pro-inflammatory cytokines TNF-α and IFN-γ and of BT upon H-TC uptake by Caco-2 cells. The proinflammatory cytokines TNF-α and IFN-γ inhibit Na-independent, non-ASBT (sodium-dependent bile acid transporter)-mediated H-TC uptake by Caco-2 cells. The inhibitory effect of these cytokines on Na-independent H-TC uptake is PI3K- and JAK/STAT1-mediated. These two compounds upregulate ASBT expression levels, but no corresponding increase in Na-dependent component of H-TC is observed. Moreover, BT was also found to inhibit H-TC uptake and showed an additive effect with IFN-γ in reducing H-TC uptake. We conclude that an interaction between BT and bile acids appears to exist in IBD, which may participate in the link between diet, microbiota and IBD.