000) at day 8. Figure 3 Gallbladder volume as a function of time after ingestion of chenodeoxycholic acid in patients with Crohn’s colitis and disease controls. Table 3 Gallbladder dynamics in patients with Crohn’s colitis and disease controls during the first 6 hours after CDCA ingestion and after 8 days of CDCA ingestion. selleck chem inhibitor Correlations between plasma FGF19 levels, gallbladder volumes and CDCA doses Although a significant increase in both GB volume and FGF19 level over the first 6 hrs after CDCA ingestion was found (Figures 2 and and3),3), there was no significant correlation between plasma FGF19 levels and corresponding GB volumes at the individual time points after the first CDCA ingestion, neither in the two subgroups nor in the total group (R varying from ?0.38 to 0.52, p>0.05).

Faecal bile acid excretion In one patient with CC, faecal bile acid excretion could not be assessed due to the absence of bowel movement on the day before the colonoscopy. Mean 24 hrs-faecal bile acid excretion after 7 days of CDCA ingestion was 2.23 mmol/24 hrs (�� SD 2.54) in CC patients and 1.86 mmol/24 hrs (�� SD 1.42) in disease controls (p=0.68). In 7 of 8 CC patients and in 10 of 12 disease controls fecal bile acid excretion exceeded normal reference values (0.0?0.4 mmol/24 hrs). Fecal bile acid excretion did not correlate with cumulative ingested CDCA dose (data not shown). No significant correlations between FGF19 levels or GB volumes after 8 days of CDCA ingestion and fecal bile acid excretion were found (data not shown).

FXR target gene expression Transcript levels of FXR and FXR target genes for the two CDCA-treated groups are given in Table 4. Ileal expression of all investigated genes was not significantly different between both CDCA-treated groups. Compared to the separate untreated disease control group, in the (combined) CDCA-treated groups mRNA expression levels of the FXR target genes IBABP (3.40 versus 0.95, p=0.00) and FGF19 (30.0 versus 0.87, p=0.00) were significantly higher, whereas mRNA levels of ASBT were lower (0.48 versus 0.89, p=0.03). Regarding FXR-dependent genes implicated in antibacterial defense: angiogenin 1 mRNA expression was significantly lower in the CDCA treated group (0.63 versus 0.88, p=0.03). mRNA expression levels of FXR, FXR target and FXR dependent genes in cecum was much lower than in ileum, without differences between CDCA-treated CC and controls (data not shown).

Table 4 Ileal mRNA expression levels of FXR and FXR target genes in patients with Crohn’s colitis and disease controls after CDCA stimulation. Discussion Since we previously observed dysregulation of FXR target gene expression in ileal biopsies of CC patients [13], in this study we aimed to explore whether pharmacological Brefeldin_A activation of ileal FXR is feasible in patients with CC. The main finding of our study is that activation of the bile acid-FXR-FGF 19 axis by the FXR ligand CDCA is feasible in patients with CC.