Transdermal fluorescence detection of a dual fluorophore system for noninvasive point-of-care gastrointestinal permeability measurement.

Richard B Dorshow,L Colleen Rouggly-Nickless,Jeng-Jong Shieh,Carla Hall-Moore,I Rochelle Riley,Nurmohammad Shaikh,Thomas E Rogers,Martin P Debreczeny,Phillip I Tarr,J R Johnson

doi:10.1364/boe.10.005103

Richard B Dorshow, L Colleen Rouggly-Nickless + Show 8 more

Open Access

https://doi.org/10.1364/boe.10.005103

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Abstract

The intestinal mucosal barrier prevents macromolecules and pathogens from entering the circulatory stream. Tight junctions in this barrier are compromised in inflammatory bowel diseases, environmental enteropathy, and enteric dysfunction. Dual sugar absorption tests are a standard method for measuring gastrointestinal integrity, however, these are not clinically amenable. Herein, we report on a dual fluorophore system and fluorescence detection instrumentation for which gastrointestinal permeability is determined in a rat small bowel disease model from the longitudinal measured transdermal fluorescence of each fluorophore. This fluorophore technology enables a specimen-free, noninvasive, point-of-care gastrointestinal permeability measurement which should be translatable to human clinical studies.

Highlights

Intestinal permeability is increased in multiple intestinal disorders, including Crohn’s Disease, celiac disease, graft vs. host disease, and environmental enteropathy and enteric dysfunction
(μg/mL) of MB-301 and MB-404 measured by the HPLC analysis, and the total mass amount recovered in the urine
The fluorophore technology was shown to be more sensitive than the dual sugar absorption test (DSAT) method in the animal model for recovery of compounds in the urine

Summary

Introduction

Intestinal permeability is increased in multiple intestinal disorders, including Crohn’s Disease, celiac disease, graft vs. host disease, and environmental enteropathy and enteric dysfunction. Permeability is increased in extra-intestinal disorders such as types I and II diabetes, nonalcoholic fatty liver disease, and juvenile and adult inflammatory arthritidies [1,2,3,4,5]. First degree relatives of people with Crohn’s Disease, who are at increased risk for the development of this disorder, have increased permeability [6,7,8]. The prevalence of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is estimated to be 1.2 million people in the US [9], and the total annual economic burden of IBD in the US is estimated to exceed $10 billion [10]. Current disease monitoring strategies are expensive (colonoscopies), invasive (blood tests), or cumbersome (stool tests)

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