Short bowel syndrome occurs when gut dysfunction results from surgical or traumatic loss. Severe dysfunction may lead to intestinal failure, characterized by prolonged dependence on parenteral nutrition and associated with high cost and multiple morbidities. When complications become life-threatening, allogeneic organ transplantation may cure intestinal failure but carries significant risks. Medical management of short bowel syndrome seeks to mitigate comorbidities while optimizing intestinal adaptation. Adaptation is characterized by progressive increase in remnant bowel size and function, leading to enteral autonomy in many but not all. Treatments that safely augment intestinal adaptation or replace lost intestinal mass would transform short bowel syndrome care.

The objective of this methods collection is to share research methodologies for studying intestinal adaptation mechanisms and modifications, pressuring and shaping proliferation or differentiation of the intestinal stem cell compartment or other crypt-villus domains, and developing materials or steps in pursuit of a functioning artificial intestine.

Augmenting and shaping the adaptive response will open new treatment pathways and paradigms in the management of this orphan disease. The GLP-2 analogue Teduglutide serves as the first example of the potential impact. Advancements in small bowel tissue engineering will one day render allogeneic bowel transplantation moot, avoiding the harms associated with immune suppression and organ rejection. In short, methodologies described today are imperative to advancing translational and clinical research and the treatments of tomorrow in this costly, rare, and life-threatening disease.