Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome

Peggy Berlin,Ursula Seidler,Manuela Bastian,Maria Witte,Änne Glass,Karen Bannert,Ernst Klar,Holger Sven Willenberg,Johannes Reiner,Brigitte Vollmar,Jakob Wobar,Georg Lamprecht,Michael Walter

doi:10.1007/s10620-018-5420-x

Peggy Berlin, Ursula Seidler + Show 11 more

Open Access

https://doi.org/10.1007/s10620-018-5420-x

Copy DOI

Abstract

BackgroundShort bowel syndrome results from extensive small bowel resection and induces adaptation of the remaining intestine. Ileocecal resection (ICR) is the most frequent situation in humans. Villus hypertrophy is one hallmark of mucosal adaptation, but the functional mechanisms of mucosal adaptation are incompletely understood.AimsThe aim of the study was to characterize a clinically relevant model of short bowel syndrome but not intestinal failure in mice and to identify outcome predictors and mechanisms of adaptation.MethodsMale C57BL6/J mice underwent 40% ICR and were followed for 7 or 14 days. Small bowel transection served as control. All mice underwent autopsy. Survival, body weight, wellness score, stool water content, plasma aldosterone concentrations, and paracellular permeability were recorded.ResultsUnlike controls, resected mice developed significant diarrhea with increased stool water. This was accompanied by sustained weight loss throughout follow-up. Villus length increased but did not correlate positively with adaptation. Plasma aldosterone concentrations correlated inversely with body weight at day 14. After ICR, intestinal epithelial (i.e., tight junctional) sodium permeability was increased.Conclusions40% ICR results in moderate to severe short bowel syndrome. Successful adaptation to the short bowel situation involves villus elongation but does not correlate with the degree of villus elongation alone. In addition, increased intestinal epithelial sodium permeability facilitates sodium-coupled solute transport. Hyperaldosteronism correlates with the severity of weight loss, indicates volume depletion, and counterregulates water loss.

Highlights

Intestinal failure is a severe condition with poor prognosis and occurs when the intestine cannot provide sufficient caloric and fluid absorption [1]
We show that 40% Ileocecal resection (ICR) induces severe short bowel syndrome with sustained stool water and body weight losses, which are counteracted by hyperaldosteronism
24 ICR and 15 sham mice were operated with the intention to survive 7 days (POD 7)

Summary

Introduction

Intestinal failure is a severe condition with poor prognosis and occurs when the intestine cannot provide sufficient caloric and fluid absorption [1]. Short bowel is one major reason of intestinal failure. Short bowel syndrome results from extensive small bowel resection and induces adaptation of the remaining intestine. Aims The aim of the study was to characterize a clinically relevant model of short bowel syndrome but not intestinal failure in mice and to identify outcome predictors and mechanisms of adaptation. Results Unlike controls, resected mice developed significant diarrhea with increased stool water. This was accompanied by sustained weight loss throughout follow-up. Conclusions 40% ICR results in moderate to severe short bowel syndrome. Successful adaptation to the short bowel situation involves villus elongation but does not correlate with the degree of villus elongation alone. Hyperaldosteronism correlates with the severity of weight loss, indicates volume depletion, and counterregulates water loss

Objectives

Methods

Results

Conclusion