Sa2030 - Measurement of Gut Permeability Using Fluorescent Tracer agent Technology

Richard Dorshow,Carla Hall-Moore,Nurmohammad Shaikh,Michael Talcott,William Faubion,Thomas E Rogers,Jeng J Shieh,Martin P Debreczeny,James R Johnson,Roy B Dyer,Ravinder J Singh,Phillip I Tarr

doi:10.1016/s0016-5085(17)31640-2

Abstract

The healthy gut restricts macromolecular and bacterial movement across tight junctions, while increased intestinal permeability accompanies many intestinal disorders. Dual sugar absorption tests, which measure intestinal permeability in humans, present challenges. Therefore, we asked if enterally administered fluorescent tracers could ascertain mucosal integrity, because transcutaneous measurement of differentially absorbed molecules could enable specimen-free evaluation of permeability. We induced small bowel injury in rats using high- (15 mg/kg), intermediate- (10 mg/kg), and low- (5 mg/kg) dose indomethacin. Then, we compared urinary ratios of enterally administered fluorescent tracers MB-402 and MB-301 to urinary ratios of sugar tracers lactulose and rhamnose. We also tested the ability of transcutaneous sensors to measure the ratios of absorbed fluorophores. Urinary fluorophore and sugar ratios reflect gut injury in an indomethacin dose dependent manner. The fluorophores generated smooth curvilinear ratio trajectories with wide dynamic ranges. The more chaotic sugar ratios had narrower dynamic ranges. Fluorophore ratios measured through the skin distinguished indomethacin-challenged from same day control rats. Enterally administered fluorophores can identify intestinal injury in a rat model. Fluorophore ratios are measureable through the skin, obviating drawbacks of dual sugar absorption tests. Pending validation, this technology should be considered for human use.

Highlights

The healthy gut restricts macromolecular and bacterial movement across tight junctions, while increased intestinal permeability accompanies many intestinal disorders
Dual sugar absorption testing is a functional assessment of permeability that compares uptake into the circulation of a synthetic disaccharide, generally lactulose (MW = 342), and a monosaccharide, usually mannitol (MW = 182) or rhamnose (MW = 164)
The fluorophore and sugar tracers differed significantly between rats challenged with high-dose indomethacin and their same day controls at most time points (Fig. 2, Supplementary Table S2)

Summary

Introduction

The healthy gut restricts macromolecular and bacterial movement across tight junctions, while increased intestinal permeability accompanies many intestinal disorders. Fluorophore ratios are measureable through the skin, obviating drawbacks of dual sugar absorption tests. Pending validation, this technology should be considered for human use. Dual sugar absorption testing is a functional assessment of permeability that compares uptake into the circulation of a synthetic disaccharide, generally lactulose (MW = 342), and a monosaccharide, usually mannitol (MW = 182) or rhamnose (MW = 164). These sugars are administered together in solution by mouth. Sugar assays increasingly use liquid chromatography/mass spectrometry[3], an analytical technology that is superior to high performance liquid chromatography[4], but which is rarely available outside research laboratories

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Conclusion