An objective in vivo diagnostic method for inflammatory bowel disease.

Sophie C Payne,James B Fallon,Alicia Sedo,Robert K Shepherd,John B Furness

doi:10.1098/rsos.180107

Abstract

Inflammatory damage to the bowel, as occurs in inflammatory bowel disease (IBD), is debilitating to patients. In both patients and animal experimental models, histological analyses of biopsies and endoscopic examinations are used to evaluate the disease state. However, such measurements often have delays and are invasive, while endoscopy is not quantitatively objective. Therefore, a real-time quantitative method to assess compromised mucosal barrier function is advantageous. We investigated the correlation of in vivo changes in electrical transmural impedance with histological measures of inflammation. Four platinum (Pt) ball electrodes were placed in the lumen of the rat small intestine, with a return electrode under the skin. Electrodes placed within the non-inflamed intestine generated stable impedances during the 3 h testing period. Following an intraluminal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), an established animal model of IBD, impedances in the inflamed region significantly decreased relative to a region not exposed to TNBS (p < 0.05). Changes in intestinal transmural impedance were correlated (p < 0.05) with histologically assessed damage to the mucosa and increases in neutrophil, eosinophil and T-cell populations at 3 h compared with tissue from control regions. This quantitative, real-time assay may have application in the diagnosis and clinical management of IBD.

Highlights

Crohn’s disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD), are debilitating episodic disorders of the gastrointestinal tract
Endoscopy is an indispensable tool for assessing the extent and severity of the inflammation and to determine responses to therapy, mucosal healing, which is considered a primary indicator of remission from IBD [6,7]
Ztotal in vivo is presumed to be dominated by the impedance of the gut wall, notably the impedance of epithelial cell barrier of the lining of the intestine, including the impedance provided by the tight junctions between epithelial cells

Summary

Introduction

Crohn’s disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD), are debilitating episodic disorders of the gastrointestinal tract. IBD typically develops in young adulthood and affects patients throughout their lives. The severity of the disease in patients is evaluated by symptomology, histology of biopsies, endoscopy and cytokine measurements [4,5]. Endoscopy is an indispensable tool for assessing the extent and severity of the inflammation and to determine responses to therapy, mucosal healing, which is considered a primary indicator of remission from IBD [6,7]. Endoscopy provides a visual assessment of gut inflammation, it needs to be supplemented by histological assessment of biopsy samples. A method that measures mucosal integrity without biopsy sampling would augment endoscopy findings

Objectives

Methods

Results