Chyme reinfusion restores the regulatory bile salt-FGF19 axis in intestinal failure patients

Automated chyme reinfusion (CR) in intestinal failure (IF) patients with a temporary double enterostomy (TDE) restores intestinal function and protects against liver injury, but the mechanisms are incompletely understood. The aim was to investigate whether beneficial effects of CR relate to functional recovery of enterohepatic signaling via the bile salt-FGF19 axis. Blood samples were collected from 12 patients, 3 days before, at start, and 1, 3, 5 and 7 weeks after CR initiation. Plasma FGF19, total bile salts (TBS), C4 (marker of bile salt synthesis), citrulline (CIT), bile salt composition, liver tests and nutritional risk indices were determined. Paired small bowel biopsies prior to CR and after 21 days were taken and genes related to bile salt homeostasis and enterocyte function were assessed. CR induced an increase in plasma FGF19 and decreased C4 levels, indicating restored regulation of bile salt synthesis via endocrine FGF19 action. TBS remained unaltered during CR. Intestinal FXR was upregulated after 21 days of CR. Secondary and deconjugated bile salt fractions were increased after CR, reflecting restored microbial metabolism of host bile salts. Furthermore, CIT and albumin levels were gradually rising after CR, while abnormal serum liver tests normalized after CR, indicating restored intestinal function, improved nutritional status and amelioration of liver injury. CR increased gene transcripts related to enterocyte number, carbohydrate handling and bile salt homeostasis. Finally, the reciprocal FGF19/C4 response after 7 days, predicted the plasma CIT time course. CONCLUSIONS: CR in IF-TDE patients restored bile salt-FGF19 signaling and improved gut-liver function. Beneficial effects of CR are partly mediated by recovery of the bile salt-FGF19 axis and subsequent homeostatic regulation of bile salt synthesis.