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Surgical Endoscopy

Published in:

01-10-2016

Effect of bowel resection on TLR signaling during intestinal adaptation in a rat model

Authors: Igor Sukhotnik, Bassel Haj, Yulia Pollak, Tatiana Dorfman, Jacob Bejar, Ibrahim Matter

Published in: Surgical Endoscopy | Issue 10/2016

Abstract

Background

Bacterial overgrowth is common complication of short bowel syndrome (SBS) and is a result of an impaired gut barrier function. Toll-like receptor 4 (TLR4) is crucial in maintaining intestinal epithelial homeostasis, participates in a vigorous signaling process and heightens inflammatory cytokine output. The objective of this study was to determine the effects of bowel resection on TLR4 signaling in intestinal mucosa in a rat model.

Methods

Male Sprague–Dawley rats were randomly assigned to one of the two experimental groups of eight rats each: Sham rats underwent bowel transection and re-anastomosis and SBS rats underwent 75 % small bowel resection. Rats were killed on day 14. Bacterial translocation (BT) to mesenteric lymph nodes, liver, portal blood and peripheral blood was determined at the kill. The expression of TLR4, MyD88 and TRAF6 in the intestinal mucosa was determined using real-time PCR, Western blot and immunohistochemistry.

Results

SBS rats demonstrated a 100 % BT to lymph nodes and to liver (Level I), 80 % translocation to portal blood (Level II) and 60 % translocation to peripheral blood (Level III) at day 7 as well as a 100 % BT to lymph nodes and liver, and 40 % translocation to peripheral blood at day 14. Microarray expression profiling demonstrated that most of the TLR signaling-related genes were up-regulated in resected rats compared to control animals. SBS rats showed a significant increase in TLR4 and TRAF6 mRNA in jejunum and ileum, TLR4 and MyD88 protein expression in jejunum and ileum, and a significant increase in the number of TLR4 and TRAF6 positive cells (immunohistochemistry) compared to sham animals.

Conclusions

In a rat model of SBS, elevated intestinal BT is associated with a stimulated TLR4 signaling.

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Title: Effect of bowel resection on TLR signaling during intestinal adaptation in a rat model
Authors: Igor Sukhotnik
Bassel Haj
Yulia Pollak
Tatiana Dorfman
Jacob Bejar
Ibrahim Matter
Publication date: 01-10-2016
Publisher: Springer US
Published in: Surgical Endoscopy / Issue 10/2016
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI: https://doi.org/10.1007/s00464-016-4760-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Effect of bowel resection on TLR signaling during intestinal adaptation in a rat model

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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