Intestinal reengineering: Scientific advances in intestinal transplantation

Intestinal transplantation (ITx) has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies. Despite its growing clinical acceptance, ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation. This review comprehensively summarizes the historical evolution, clinical indications, and advancements in surgical techniques, with emphasis on innovations in vascular anastomosis, multivisceral transplantation, and <i>ex vivo</i> preservation. Special attention is given to the unique immunological challenges of ITx, including bidirectional immune responses-host-<i>vs</i>-graft and graft-<i>vs</i>-host disease-immune-microbiota interactions, and the distinct roles of key immune cells. Pediatric and adult recipients exhibit divergent etiologies, immune responses, and complication profiles, necessitating individualized approaches. Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes, chronic rejection, graft dysfunction, and immunosuppressive toxicity remain significant barriers. Looking ahead, future directions should prioritize precision immunomodulation, microbiome-targeted therapies, and integrated platforms for gene editing, 3D bioprinting, and immune monitoring. Through multidisciplinary collaboration and translational research, ITx is poised to evolve from a high-risk salvage therapy into a personalized, sustainable solution that enhances long-term survival and patient quality of life.