Noninvasive Point-Of-Care Measurement Of Gastrointestinal Permeability

The intestinal mucosal barrier prevents macromolecules and pathogens from entering the circulatory stream in a healthy gut. Tight junctions in this barrier are compromised in many intestinal disorders including inflammatory bowel diseases (such as Crohn's and ulcerative colitis), celiac disease, graft vs host disease, environmental enteropathy, and enteric dysfunction. Dual sugar absorption tests are a standard method for measuring gastrointestinal integrity in humans. The larger molecular weight sugar, lactulose, is minimally absorbed through a healthy gut. The smaller molecular weight sugar, mannitol or rhamnose, in contrast, is readily absorbed through both a healthy and inflamed gut. Thus, a higher ratio of lactulose to mannitol or rhamnose reflects increased intestinal permeability. However, several issues prevent the widespread use of the dual sugar assay including requirements for lengthy urine collection, transport of specimens under conditions free from contamination and bacterial growth, analysis by sophisticated laboratory equipment, and the associated lengthy turnaround time. In a recent publication, the feasibility of employing a dual fluorescent tracer agent assay to mimic the dual sugar absorption test without the need for specimen collection was reported. This dual fluorophore assay for GI permeability was demonstrated in an indomethacin-induced bowel disease model in rats. However, one of the fluorophores was not entirely biocompatible. Herein is reported a dual fluorophore system that is totally biocompatible, with emphasis on the transdermal detection of the fluorophores, thus enabling the use of the technology for noninvasive point-of-care gastrointestinal permeability determination.