Home parenteral nutrition (HPN) has saved the lives of thousands of short bowel syndrome (SBS) patients with intestinal failure (IF) since the introduction in the late 1960s. SBS-IF patients have inadequate absorption of fluid, electrolytes, macronutrients, trace elements, or vitamins to meet their metabolic requirements and fail to maintain their hydration, body composition, function, and health without parenteral support (PS). In adults, SBS is most frequently seen following intestinal resections due to inflammatory bowel disease (IBD), mesenteric vascular disease, complications to non-IBD surgery (ileus, volvulus, leakage of anastomoses, etc.), and complications to treatment of cancers, whereas in children, resections are also seen as a consequence of congenital defects or necrotizing enterocolitis. However, extensive parenchymal and mucosal disease of the bowel may also diminish the absorptive capacity of the bowel – in the absence of resection – and lead to “functional short bowel syndrome” and IF.
The short bowel syndrome could be considered as a spectrum, where SBS patients with intestinal insufficiency are able to compensate for their malabsorption by increasing oral intake (hyperphagia) and adapt metabolically or pharmacologically, whereas SBS patients with intestinal failure (SBS-IF) require supplemental or total PS. It is clear that, although all patients with intestinal resections and malabsorption are included in the same syndrome, they are truly heterogeneous and present with many phenotypes as described in a recent review.
Although providing a lifesaving option in the home environment of the SBS-IF patient, these patients are not only challenged by the inconveniences and symptoms of their gastrointestinal disorder but also by the fear of – or the factual burden of – the potentially life-threatening complications of HPN. Therefore, treatments should seek to maximize remnant intestinal absorption, decrease malabsorption and accompanying symptoms, and reduce the fear, burdens, or complications related to HPN, thereby ultimately improving the health-related quality of life in SBS-IF patients.
In general, treatments aiming to increase intestinal absorption have consisted of dietary advice in conjunction with a limited pharmacological treatment armamentarium, mainly including antisecretory and antidiarrheal agents. Only few centers taking care of SBS patients have the facilities, methods, and resources to objectively assess effects of interventions on intestinal absorption in the individual patients. With the large interpatient treatment-effect variability in relation to interventions, mainly due to the large patient heterogeneity, the evaluations of the true effects of each of the components of the multidimensional treatment approach frequently rely on subjective global assessments by the physician and on the patients feedback rather than on objective measurements of intestinal function. In general, the maximal intestinal digestion and absorption is sought by maximizing the exposure of the mucosal surface area to nutrients, fluids, electrolytes, trace elements, and vitamins in the right form, concentration, and composition, at the right place, in the right environment, and in a timely fashion as described in a recent review.
Over the past decades, it has become increasingly clear that mucosal nerve ends and endocrine cells within the gastrointestinal tract mediate information via the enteric nervous system in response to the passing of luminal contents, thereby contributing to the highly coordinated processes of nutrient assimilation. These “neuroendocrine feedback mechanisms” often referred to as the “gastric, jejunal, ileal, or colonic brakes” may be disrupted by intestinal resections or mucosal disease. The attenuation of the meal-stimulated secretion of hormones, such as the glucagon-like peptides (GLPs) 1 and 2 and peptide YY by L cells in the terminal ileum and the colon, may be associated with some of the pathophysiological features of SBS patients with distal bowel resections: accelerated gastrointestinal motility, gastric and intestinal hypersecretion, diminished intestinal blood flow, disturbed immunological and barrier functions, and impaired mucosal replacement, repair, and adaptation. In SBS patients with a terminal ileum or colon in continuity, an increase in the endogenous hormonal secretion may be responsible for the progressive intestinal adaptation believed to occur in these patients.
Consequently, these observations have instigated the pharmacological use of hormonal factors in the intestinal rehabilitation of SBS patients. The first peptide hormone to gain marketing approval for the treatment of SBS patients is the GLP-2 agonist teduglutide. Teduglutide has recently gained approval by the US Food and Drug Administration and European Medicines Agency. NPS Pharmaceuticals has marketed teduglutide as Gattex® in the United States and seek to market teduglutide as Revestive® in Europe in the near future. When introducing new therapies, it is prudent to evaluate and balance the benefit or clinical meaningfulness of interventions versus the inconveniences, adverse effects, risks, and costs. This chapter describes the results of the clinical trials of native GLP-2 and of teduglutide, leading to marketing approval of the latter for the treatment of SBS patients, in this respect.
Palle Bekker Jeppesen