The Hormonal Effect of Fibroblast Growth Factor 19 on the Intestinal Adaptation in Pediatric Short Bowel Syndrome: An in Vitro Study Using Patients-derived Enteroids

Abstract

Background

Promoting intestinal adaptation is of paramount importance for restoring normal gastrointestinal function in pediatric patients with short bowel syndrome (SBS). However, the hormonal effect of fibroblast growth factor 19 (FGF19) on the intestinal adaptation of SBS patients remains unknown.

Methods

Integrated analyses using transcriptomic profiles were performed across two datasets. In vivo datasets were obtained from a group of pediatric SBS patients without intact ileocecal valve (ICV) exhibiting immature gut function and reduced FGF19 levels (n = 5), compared to their counterparts with ICV (n = 4). In vitro datasets were obtained from SBS patients-derived enteroids (SBS-PDEs) treated with recombinant human FGF19 (rhFGF19).

Results

As a result, 2680 differentially expressed genes (DEGs) were identified in vivo, most of which could be clustered into “metabolic pathway” and “cell adhesion”; 410 DEGs were identified in vitro, most of which could be clustered into “extracellular matrix organization” and “cell adhesion”. In SBS-PDEs, treatment with rhFGF19 significantly enhanced the integrity of epithelial barrier function, and substantially improved the mitochondrial respiration function. Notably, there were 56 overlapped DEGs identified both in vitro and in vivo, most of which could be clustered into “cell adhesion”.

Conclusions

Beyond metabolic regulation, the hormonal effect of FGF19 on the maturation of intestinal epithelium may also include enhancing epithelial barrier function, improving mitochondrial respiration function, and regulating cell adhesion.