TED_ORG: Study on Short Bowel Syndrome

The goal of this clinical trial is to understand why pediatric patients with short bowel syndrome respond differently to treatment with the glucagon-like peptide-2 (GLP-2) analogue teduglutide. Short bowel syndrome is a rare and severe condition in children that results from extensive intestinal resection and leads to impaired nutrient absorption, chronic diarrhea, and dependence on parenteral nutrition. Although teduglutide is known to promote intestinal adaptation and improve absorption, the clinical response varies widely among patients, and the biological mechanisms underlying this variability are not fully understood. This study aims to investigate the effects of teduglutide using human intestinal organoids derived from intestinal tissue samples of pediatric patients with short bowel syndrome. Intestinal organoids are three-dimensional structures grown from patient-derived stem cells that reproduce key structural and functional characteristics of the human intestine. These organoids provide a human-based experimental model that allows the study of intestinal morphology, cellular behavior, and nutrient absorption in a controlled in vitro environment. The main questions this study aims to answer are: Does treatment with teduglutide improve the absorptive capacity of human intestinal organoids derived from pediatric patients with short bowel syndrome? Are there differences in intestinal structure, cellular proliferation, and gene expression between teduglutide-treated organoids and untreated organoids? Are specific molecular or cellular features associated with different responses to teduglutide? Researchers will compare intestinal organoids treated with teduglutide to untreated organoids obtained from the same patients. This comparison will be used to evaluate changes in organoid morphology, expression of receptors involved in intestinal growth and absorption, activity of nutrient transporters, and overall absorptive function. The study will also explore differences between organoids derived from patients who show different clinical responses to teduglutide. Participants in this study are pediatric patients with short bowel syndrome or patients undergoing intestinal resection surgery as part of their standard clinical care. No experimental treatment is administered directly to participants as part of this study. Intestinal tissue samples are collected only during clinically indicated surgical procedures and are not obtained specifically for research purposes. Participants will: Provide intestinal tissue samples collected during routine or clinically indicated intestinal surgery Have intestinal organoids generated from their tissue samples using established laboratory techniques Have their organoids studied in vitro with and without exposure to teduglutide to evaluate intestinal structure, gene and protein expression, and nutrient absorption mechanisms The results of this study are expected to improve understanding of the biological mechanisms underlying variable responses to teduglutide and may contribute to the development of more personalized treatment strategies for pediatric patients with short bowel syndrome in the future.