Molecular Mechanisms of Intestinal Adaptation in Short Bowel Syndrome: A Comprehensive Review

Short bowel syndrome (SBS) develops when the remaining intestine is unable to sustain adequate nutrient and electrolyte absorption following extensive bowel resection. The condition is characterized by malabsorption and significant fluid losses which lead to dehydration and progressive weight loss, thus promoting patient dependence on parenteral fluids or nutrition. After an initial acute phase marked by accelerated intestinal transit and gastric hypersecretion, long-term clinical outcomes are largely determined by the capacity of the remaining bowel for intestinal adaptation-a sustained process of structural, functional, and molecular remodeling that enhances absorptive efficiency and restores fluid and nutrient homeostasis. This review summarizes the key histological and cellular features of the adaptive response, including crypt and villus remodeling, mucosal hyperplasia, and smooth muscle hypertrophy, and integrates emerging concepts in crypt biology that define the dynamic cross-talk between intestinal stem cells and the mesenchymal niche, together with their upstream regulatory pathways.