Impact of elobixibat on serum and fecal bile acid levels and constipation symptoms in patients with chronic constipation

Background and Aim: Elobixibat is a locally acting inhibitor of the ileal bile acid transporter. We compared bile acid metabolism between healthy subjects and patients with chronic constipation and assessed changes in the bile acid profile after elobixibat administration in the latter group. Methods: Healthy subjects (n = 10) and patients with chronic amstipation (n = 19) were assessed as inpatients for 7 days, during which they received meals containing similar to 60 g/day of fat. Patients with chronic constipation remained as inpatients for a further 7 days for once-daily elobixibat administration. Assessments included concentrations of fecal and serum bile acids, serum 7 alpha-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19, and bowel movements and constipation symptoms. Results: Fecal total and primary bile acids were significantly lower in patients with chronic constipation versus healthy subjects. Serum C4 and fibroblast growth factor 19 levels were comparable between groups. Elobixibat treatment increased fecal total and primary bile acids and decreased levels of fecal lithocholic acid and serum total as well as secondary bile acids in patients with chronic constipation. Bowel movements and other constipation-related symptoms were also improved by elobixibat to levels almost comparable with those of healthy subjects. Conclusions: Despite comparable C4 levels, patients with chronic constipation demonstrated decreased levels of fecal bile acids versus healthy subjects. Elobixibat treatment increased fecal bile acid excretion and reduced serum bile acid concentrations. The improvement of constipation after elobixibat treatment was associated with increased total bile acids, particularly primary bile acids.