Short- and long-term effects of small bowel resection: a unique histological study in a piglet model of short bowel syndrome

Abstract

If we are to develop successful interventions to improve clinical outcomes for short bowel syndrome patients we require (1) knowledge of changes within the epithelial population following small bowel resection (SBR) and (2) an idea of when these changes occur to inform on the timing of potential interventions aimed at enhancing the adaptive response. The aim of this study was to produce a temporal map of epithelial changes within the crypt and villus at early and late adaptation phases. Four-week-old piglets underwent a 75% SBR or sham operation and were studied at 2, 4 and 6 weeks post-operation to allow analysis of early and late adaptation responses. Piglets received polymeric infant formula (PIF). Immunohistochemistry with specific cell markers was used to quantitate intestinal cell types and the total cell numbers. Changes within the crypt were temporally dependent on an early significant increase in enterocytes and proliferative cells not sustained at 6 weeks. Goblet cell numbers were increased at all time points. Despite a significant increase in total villus cell numbers at 6 weeks there was no change in specific cell types. We observed two distinct phases of cellular change following SBR. An early increase in enterocytes and proliferative cells was not reflected in increased weight gain indicating the early increase represents immature enterocytes. Interventions aimed at increasing differentiation of the rapidly changing crypt population would allow for an earlier increase in absorption.

Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration

“…There was no difference in goblet cells per hemivillus between sham and SBS groups. Previous studies have reported significant increase in goblet cell density in mouse and pig SBS models (17,33), but increases in goblet cells are also noted in response to ATOH1 and SPDEF (12,21).…”

“…The majority of investigations involve 50% or greater small bowel resection (SBR) in mouse, rat, and pig models. Piglet models benefit from the larger size of the animals, which allows a technically easier bowel resection and anastomosis, and authors also cite more anatomical, physiological, and biochemical similarities to newborn human infants than rodent models (33). However, housing, procurement, and surgical supplies are more expensive, typically thousands of dollars per piglet.…”

Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome

“…Piglets were fed a polymeric infant formula diet (Karicare De-Lact, Nutricia) supplemented to meet the daily requirements for piglets as described previously. 11,37,38 The diets were isocaloric and isonitrogenous among the groups and were administered on a per kilogram basis. Water was given twice daily.…”

“…Colonic tissue was collected 3 cm and 10 cm distal to the cecum in the two-week and six-week groups, respectively, at locations optimised for age, as based on a previous study. 37 A 3 cm section from each site was divided in half longitudinally and fixed in 10% neutral buffered formalin (Australian Biostain Pty. Ltd.) or snap frozen in liquid nitrogen.…”

Models of Short Bowel Syndrome in Pigs: A Technical Review

“…In the last decade, modern therapeutic options such as tissue engineering [9] have been among the topics of interest. Due to the anatomical and physiological similarities to humans, porcine models are useful for optimizing different therapeutic approaches [10,11,12,13,14]. There are various and sometimes not exact definitions of SBS in the literature.…”