Measurement of gut permeability using fluorescent tracer agent technology

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 ad...

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Bibliographic Details
Published in:Scientific reports 2017-09, Vol.7 (1), p.10888-8, Article 10888
Main Authors: Dorshow, Richard B., Hall-Moore, Carla, Shaikh, Nurmohammad, Talcott, Michael R., Faubion, William A., Rogers, Thomas E., Shieh, Jeng Jong, Debreczeny, Martin P., Johnson, James R., Dyer, Roy B., Singh, Ravinder J., Tarr, Phillip I.
Format: Article
Language:English
Subjects:
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Absorption
Digestive system
Fluorescent indicators
Fluorophores
Gastrointestinal tract
Humanities and Social Sciences
Indomethacin
Lactulose
Macromolecules
Mucosa
multidisciplinary
Permeability
Rhamnose
Rodents
Science
Science (multidisciplinary)
Skin
Small intestine
Sugar
Tight junctions
Tracers
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-09971-y