Intestinal manipulation affects mucosal antimicrobial defense in a mouse model of postoperative ileus.

Jan Wehkamp,Mariola Lysson,Annette Moter,Judith Kikhney,Mathias Chamaillard,Burkhard Stoffels,Sven Wehner,Lena Hieggelke,Joerg C Kalff,Sabine Nuding,Bianca Schneiker,Kathy Stein

doi:10.1371/journal.pone.0195516

Abstract

AimTo explore the effects of abdominal surgery and interleukin-1 signaling on antimicrobial defense in a model of postoperative ileus.MethodsC57BL/6 and Interleukin-1 receptor type I (IL-1R1) deficient mice underwent intestinal manipulation to induce POI. Expression of mucosal IL-1α, IL-1β and IL-1R1 and several antimicrobial peptides and enzymes were measured by quantitative PCR or ELISA, western blotting or immunohistochemistry. Bacterial overgrowth was determined by fluorescent in-situ hybridization and counting of jejunal luminal bacteria. Translocation of aerobic and anaerobic bacteria into the intestinal wall, mesenteric lymph nodes, liver and spleen was determined by counting bacterial colonies on agar plates 48h after plating of tissue homogenates. Antimicrobial activity against E. coli and B. vulgatus was analyzed in total and cationic fractions of small bowel mucosal tissue homogenates by a flow cytometry-based bacterial depolarization assay.ResultsJejunal bacterial overgrowth was detected 24h after surgery. At the same time point, but not in the early phase 3h after surgery, bacterial translocation into the liver and mesenteric lymph nodes was observed. Increased antimicrobial activity against E. coli was induced within early phase of POI. Basal antimicrobial peptide and enzyme gene expression was higher in the ileal compared to the jejunal mucosa. The expression of lysozyme 1, cryptdin 1, cryptdin 4 and mucin 2 were reduced 24h after surgery in the ileal mucosa and mucin 2 was also reduced in the jejunum. Postoperative IL-1α and IL-1β were increased in the postoperative mucosa. Deficiency of IL-1R1 affected the expression of antimicrobial peptides during homeostasis and POI.ConclusionSmall bowel antimicrobial capacity is disturbed during POI which is accompanied by bacterial overgrowth and translocation. IL-1R1 is partially involved in the gene expression of mucosal antimicrobial peptides. Altered small bowel antimicrobial activity may contribute also to POI development and manifestation in patients undergoing abdominal surgery.

Highlights

Post-operative ileus (POI) is an iatrogenic impairment of propulsive gastrointestinal motility, frequently occurring after abdominal surgery
Small bowel antimicrobial capacity is disturbed during POI which is accompanied by bacterial overgrowth and translocation
IL-1R1 is partially involved in the gene expression of mucosal antimicrobial peptides

Summary

Introduction

Post-operative ileus (POI) is an iatrogenic impairment of propulsive gastrointestinal motility, frequently occurring after abdominal surgery. The impaired postoperative motility leads to passage disturbances which is discussed to results in bacterial overgrowth and some studies detect impaired mucosal barrier integrity after surgery [5, 6]. Translocation of microorganisms [7] from the intestinal lumen into the sterile bowel wall or distant organs aggravates the risk of inflammation which further compromises the intestinal barrier. This vicious cycle of increasing inflammation and decreasing barrier integrity can result in systemic infection and multiple organ dysfunctions [8]

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Conclusion