Clinical challenges of short bowel syndrome and the path forward for organoid-based regenerative medicine

Short bowel syndrome (SBS) is a rare condition, the main symptom of which is malabsorption following extensive resection of the small intestine. Treatment for SBS is mainly supportive, consisting of supplementation, prevention and treatment of complications, and promotion of intestinal adaptation. While development of parenteral nutrition and drugs promoting intestinal adaptation has improved clinical outcomes, the prognosis of patients with SBS remains poor. Intestinal transplantation is the only curative therapy but its outcome is unsatisfactory. In the absence of definitive therapy, novel treatment is urgently needed. With the advent of intestinal organoids, research on the intestine has developed remarkably in recent years. Concepts such as the "tissue-engineered small intestine" and "small intestinalized colon," which create a functional small intestine by combining organoids with other technologies, are potentially novel regenerative therapeutic approaches for SBS. Although they are still under development and there are substantial issues to be resolved, the problems that have prevented establishment of the complex function and structure of the small intestine are gradually being overcome. This review discusses the current treatments for SBS, the fundamentals of the intestine and organoids, the current status of these new technologies, and future perspectives.