Endogenous peptides and peptide therapy in gut defense and repair

The gastrointestinal tract shows a remarkable ability to withstand injury. Factors important in maintaining integrity include rapid proliferation, an excellent blood supply and, in the stomach and colon, the presence of a protective mucus layer. When an injury occurs, the healing process consists of an initial phase of cell migration (restitution), followed by an increase in proliferation and remodeling. There is now a large body of evidence suggesting that at least 30 different peptides are involved in maintaining mucosal integrity and in stimulating the repair process. Insights into the pathophysiological function of these peptides can be gained from considering them as belonging to broad groups based on their overall role in maintaining gut growth or in stimulating repair. Considered in this way, they can be usefully compartmentalized into: 1) mucosal integrity peptides, which are predominantly involved in maintaining normal mucosal integrity; 2) luminal surveillance peptides, which are constantly present in the lumen but which only stimulate proliferation and repair at sites of injury; and 3) rapid response peptides, whose production is rapidly regulated at sites of injury and the function of which is to stimulate the repair process. If peptide therapy for gastrointestinal conditions is to be used, potential methods of delivery include oral, systemic and gene therapy; however, orally delivered peptides may be digested in the gut lumen, systemic administration may result in side effects at sites distant to the gut and methodological problems remain when considering gene therapy. Peptides play a key role in maintaining mucosal homeostasis in the gut. Over the next five years, recombinant peptides are likely to be increasingly used to treat a wide variety of gastrointestinal disorders such as inflammatory bowel disease and necrotizing enterocolitis.