D2 | Abstract 03

Annual NUTRIM Symposium 18 November 2020


The effect of chyme reinfusion on the bile salt/fibroblast growth factor 19 signaling axis in intestinal failure patients with a temporary jejunal double enterostomy

Xinwei Chang1,5, Denis Picot2, Kiran V.K. Koelfat1,5, Sander M.J. van Kuijk3, Sabrina Layec2, Marie Carsin2, Laurence Dussaulx2, Eloi Seynhaeve2, Florence Trivin2, Laurence Lacaze4, Ronan Thibault4, Frank G. Schaap5,6, Steven W.M. Olde Damink1,5,6

1Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.
2Department of Nutritional and Digestive Rehabilitation, Clinique Saint Yves, Rennes, France.
3Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, The Netherlands.
4Nutrition Unit, CHU Rennes, Univ de Rennes, NuMeCan Institute, INSERM, INRA, Univ Rennes, Rennes, France.
5Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
6Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Aachen, Germany.

Background and Aims:
Temporary jejunal double enterostomies may result in intestinal failure (IF) and require parenteral nutrition (PN). IF-associated liver disease is multifactorial, and involves PN and enterohepatic circulation (EHC) disruption. Chyme reinfusion (CR) improves IF, liver abnormalities and restores EHC. Bile salts are signaling molecules undergoing EHC and negatively regulate their own synthesis via endocrine FGF19 produced in the ileum. We tested the hypothesis that functional restoration of EHC and attendant bile salt/FGF19 signaling contributes to the beneficial effects of CR.

IF patients with a double jejunal enterostomy on PN were recruited for CR treatment (RESCUE study: ClinicalTrial.gov NCT02990195). Blood samples were collected prior to, at start, and 1, 3, 5 and 7 weeks after CR initiation. Ileum biopsies were taken prior to and 3 weeks after CR start. Plasma levels of FGF19, total bile salts (TBS), 7alpha-hydroxy-4-cholesten-3-one (C4, a marker of bile salts synthesis), citrulline, bile salt composition, and serum liver injury and cholestasis markers were determined. A linear mixed model was used to evaluate the relationship between citrulline, TBS and FGF19 and biochemical/clinical outcomes.

Twelve adult patients were included. The hypoalbuminemia, elevated serum cholestasis (GGT, ALP) and liver injury (ALT, AST) markers normalized after CR. CR resulted in improved intestinal function, as inferred from elevated plasma citrulline and enhanced mRNA expression of epithelium-specific genes (e.g. FXR, OSTa/b). Plasma FGF19 was increased after CR and peaked after 1 week. Plasma C4 which was elevated at baseline was normalized, and circulating TBS levels were reduced. The increased fractions of unconjugated and secondary bile salts reflected restored contact between bile and gut microbiota.

CR treatment improves liver and intestinal function in IF patients with a jejunal enterostomy. The beneficial effect of CR is partly mediated by bile salt/FGF19 signaling, resulting in restored homeostatic regulation of bile salt synthesis

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