title: Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome: translational relevance and challenges.
abstract: Intestinal failure (IF), due to short bowel syndrome (SBS), results from surgical resection of a major portion of the intestine, leading to reduced nutrient absorption and need for parenteral nutrition (PN). The incidence is highest in infants and relates to preterm birth, necrotizing enterocolitis, atresia, gastroschisis, volvulus, and aganglionosis. Patient outcomes have improved, but there is a need to develop new therapies for SBS and to understand intestinal adaptation after different diseases, resection types, and nutritional and pharmacological interventions. Animal studies are needed to carefully evaluate the cellular mechanisms, safety, and translational relevance of new procedures. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult). Clinically relevant therapies have recently been suggested from studies in preterm and term PN-dependent SBS piglets, with or without a functional colon. Studies in rats and mice have specifically addressed the fundamental physiological processes underlying adaptation at the cellular level, such as regulation of mucosal proliferation, apoptosis, transport, and digestive enzyme expression, and easily allow exogenous or genetic manipulation of growth factors and their receptors (e.g., glucagon-like peptide 2, growth hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g., PN, milk diets, long-/short-chain lipids, pre- and probiotics). Conversely, newborn pigs (preterm or term) and weanling rats provide better insights into the developmental aspects of treatment for SBS in infants owing to their immature intestines. The review shows that a balance among practical, economical, experimental, and ethical constraints will determine the choice of SBS model for each clinical or basic research question.
authors.affiliation: Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark; Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark; psa@life.ku.dk.
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin;
authors.forename: Denise M
authors.initials: DM
authors.lastname: Ney
authors.affiliation: Sidra Medical and Research Center, Doha, Qatar;
authors.forename: David L
authors.initials: DL
authors.lastname: Sigalet
authors.affiliation: Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark; Diabetes Pharmacology, Novo Nordisk, Måløv, Denmark; and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Vegge
authors.affiliation: USDA-ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Douglas
authors.initials: D
authors.lastname: Burrin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007223:Infant; D051379:Mice; D010289:Parenteral Nutrition, Total; D051381:Rats; D012778:Short Bowel Syndrome / Q000503:physiopathology* / Q000628:therapy
keywords: glucagon-like peptide 2; intestine; mouse; newborn; parenteral and enteral nutrition; pig; rat; resection