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

Yiming Gong; Yang Wang; Yuling Zhao; Junkai Yan; Tian Zhang

doi:10.1016/j.jpedsurg.2025.162387

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

J Pediatr Surg. 2025 May 26;60(8):162387. doi: 10.1016/j.jpedsurg.2025.162387. Online ahead of print.

Authors

Yiming Gong¹, Yang Wang², Yuling Zhao¹, Junkai Yan³, Tian Zhang⁴

Affiliations

¹ Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
² Department of Intervention and Vascular Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
³ Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China. Electronic address: yanjunkai@xinhuamed.com.cn.
⁴ Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China. Electronic address: zhangtian0831@alumni.sjtu.edu.cn.

PMID: 40436332
DOI: 10.1016/j.jpedsurg.2025.162387

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.

Keywords: Enteroids; Fibroblast growth factor 19; Gut maturation; Intestinal adaptation; Short bowel syndrome.