Mechanisms of intestinal adaptation in short bowel syndrome: what is the evidence?

Short bowel syndrome (SBS) is defined by a remaining small bowel length of less than 200 cm after surgical resection and is a condition with significant clinical implications and a high risk of developing chronic intestinal failure. However, our understanding of intestinal adaptation, a natural process to enhance absorption of nutrients and fluids after resection, remains limited. Intestinal adaptation occurs at both structural (eg, mucosal hyperplasia) and functional (eg, altered transit and enhanced epithelial transporter expression) levels, although most insights stem from animal research and the molecular mechanisms driving these processes are not yet fully understood. This review integrates current evidence on intestinal adaptation in patients with SBS and highlights the critical role of animal models in understanding the underlying mechanisms but also underlines the need for longitudinal studies in human patients. While the diversity of available animal models provides opportunities to investigate key pathways, the variability in residual intestinal length complicates our understanding of the molecular pathways. Based on existing data, we propose that intestinal adaptation is a time-dependent process, with the most pronounced changes occurring early after resection and is affected by the remaining anatomy of the GI tract. Advancing knowledge in these areas is essential for identifying novel therapeutic targets and improving outcomes for patients with SBS.