Disease-modifying therapies in short bowel syndrome

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Abstract

Short bowel syndrome (SBS) is the main cause of chronic intestinal failure (IF), defined as ‘the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth’. SBS is a rare disease requiring a multidisciplinary approach in specialized IF units. The aim of this review was to discuss the current pharmacological management of SBS-associated IF, since emerging treatments are currently modifying the natural evolution of these patients. Enterohormone therapy has become the first-choice treatment and may decrease the need for parenteral support and improve patients' quality of life.

Introduction

Short bowel syndrome (SBS) is a rare disease resulting from extensive intestinal resection, and it is the main cause of chronic intestinal failure (IF) in adults.

IF is defined as “the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth”, and can be classified into 3 subgroups: type I (acute, short-term condition), type II (prolonged acute condition) and type III (chronic condition) [1].

The causes of SBS are varied (e.g., mesenteric ischemia, Crohn's disease, radiation enteritis, surgical complications …), and mostly benign (patients with SBS secondary to radiation enteritis are in remission or cured of their cancer). The prevalence of this disease is not well known, in particular, because of its great variability between countries. However, the exact incidence of SBS from benign causes is estimated at 2/million/year [2].

The severity of SBS is related to its etiology, remnant small bowel length, and bowel anatomy after resection. Indeed, SBS can be divided into three anatomical subtypes (Figure 1): end jejunostomy, jejunocolic anastomosis (where part of the colon is in continuity with the remnant small bowel), and jejunoileal anastomosis (where the colon and the ileocecal valve are preserved) [3].

Intestinal resection may lead to IF that is managed with parenteral nutrition (PN), which provides energy, fluid, and electrolyte needs to patients.

Section snippets

Physiology and spontaneous adaptation

Following intestinal resection, several response mechanisms take place in patients in three phases:

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    The acute phase (lasting about 4–6 weeks after resection), where gastric hypersecretion can result in diarrhea with important fluid and electrolyte loss. The challenge during this phase is to compensate dehydration and monitor the micro- and macronutrient deficiencies.

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    The adaptation phase takes place up to 12–24 months after resection, and is characterized by the implementation of spontaneous

Management of gastrointestinal symptoms

In addition to the spontaneous mechanisms observed in the bowel after resection, that may be beneficial to the patient, some GI symptoms may be managed with adequate treatment.

Pharmacological management: a new place for growth factors

In recent years, GI peptide hormones have raised particular interest in the research and clinical management of SBS patients. Since their use could change the course of the disease, some of them are now part of the therapeutic arsenal, and others are under investigation.

Two proglucagon-derived enterohormones have been widely investigated, especially because of their trophic effect on the gut mucosa. Indeed, proglucagon gene encodes for 3 peptides, namely glucagon, GLP-1 and GLP-2, which share

Conclusion

SBS is a rare complex disorder due to multiple etiologies, that requires a multidisciplinary management. PN is the reference treatment in patients with chronic IF due to SBS and can lead to several long-term complications in addition to a significantly impaired QoL. The advent of GLP-2 analogs that may change the prognosis of patients is adding a new dimension to the pharmacological management of SBS. Enterohormone therapy is undoubtedly the new cornerstone in SBS-IF. Based on the results of

Funding

This manuscript has not been funded.

Conflict of interest statement

B.D. received a grant from Takeda for the implementation of a clinical study.F.J. has participated in NPS Pharmaceuticals' Scientific, Shire's Advisory Board, Takeda, Zealand and Vectibio advosiry boards and in randomized controlled clinical trials of teduglutide supported by NPS and takeda, and randomized controlled clinical trials for Zealand (for Glepaglutide) and Vectivbio (Apraglutide).

Writing assistance

Sophie Pégorier.

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