Defective FXR-FGF15 signaling and bile acid homeostasis in cystic fibrosis mice can be restored by the laxative polyethylene glycol.

Defective FXR-FGF15 signaling and bile acid homeostasis in cystic fibrosis mice can be restored by the laxative polyethylene glycol. Am J Physiol Gastrointest Liver Physiol. 2019 Jan 17;: Authors: Bertolini A, van de Peppel IP, Doktorova-Demmin M, Bodewes FAJA, de Jonge HR, Bijvelds MJC, Verkade HJ, Jonker JW Abstract The gastrointestinal phenotype of cystic fibrosis (CF) features intestinal bile acid (BA) malabsorption, impaired intestinal farnesoid X receptor (FXR) activation and consequently reduced fibroblast growth factor 19 (FGF19, FGF15 in mice) production. The osmotic laxative polyethylene glycol (PEG) has been shown to decrease intestinal mucus accumulation in CF mice and could, by doing so, improve BA reabsorption. Here we determined the effect of PEG on BA excretion and FXR-FGF15 signaling in CF mice. Male Cftr-/-tm1Unc (CF) and wild type (WT) littermates were administered PEG 4000 in drinking water and fed either chow or a semisynthetic diet. PEG was withdrawn for three days before termination. Fecal BA excretion was measured at PEG dosages of 37 g/L (100%) and 0 g/L (0%). Ileal FXR activation was assessed by gene expression of its downstream targets Fgf15 and Shp. In CF mice, PEG withdrawal increased fecal BA excretion on either diet as compared to full PEG dosage (chow, 2-fold, p=0.06; semisynthetic, 4.4-fold, p=0.007). PEG withdrawal did not affect fecal BA excretion in WT mice on either diet. After PEG withdrawal, gen...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research