Intestinal adaptation: Structure, function, and regulation

After massive small bowel resection (SBR), the remnant intestine undergoes an adaptive process characterized by increases in wet weight, protein and DNA content, villus height and crypt depth, and absorptive surface area. These changes are the result of a proliferative stimulus that increases crypt cell mitosis and augments cellular progression along the villus axis. Functionally, there is upregulation of the Na⁺/glucose cotransporter, Na⁺/H⁺ exchanger, and other enzymes involved in intestinal digestion and absorption. These physiologic events are a compensatory response to the sudden loss of digestive and absorptive capacity by the remnant intestine. A major consequence of inadequate intestinal adaptation is lifelong dependence on parenteral nutrition, which results ultimately in cholestatic liver dysfunction. Furthermore, adaptation may be associated with changes in intestinal permeability and an increased risk of bacterial translocation and sepsis. Several mediators thought to be integral to the postresection adaptive response have been proposed, including luminal nutrients, gastrointestinal secretions, and humoral factors. A thorough understanding of intestinal adaptation will be essential in the rational development of new and innovative therapies that amplify this complex but important process.