UC Santa Cruz

Gastrointestinal barrier dysfunction is now recognized as an early event in the pathogenesis of several problematic diseases, such as inflammatory bowel disease (IBD), Parkinson’s disease, Crohn’s disease, celiac disease and type 1, 2 diabetes mellitus. Gastrointestinal permeability can be assessed noninvasively by analyzing saccharide markers in urine such as sucrose, lactulose, mannitol, and the synthetic sweetener sucralose. Current methods for analyzing these markers require expensive and time-consuming instrumentation such as high-performance liquid chromatography/mass spectrometry (LC/MS). An alternative approach has been taken by assembling a two-component fluorescent probe that comprises a boronic acid substituted bipyridinium salt (BBV) as the receptor and a fluorescent reporter dye (HPTS) in which the system operates at physiological pH. We have shown that using our two component probe small intestinal permeability can be determined by rapidly measuring the lactulose and riboflavin ratios. To improve the current system, we pursued an array based system containing a triad of the boronic acid sugar receptors. Through this array, it was possible to discriminate between low and increased small intestinal permeability by analyzing various lactulose and mannitol mixtures. Additionally, an assay to measuring sucralose for colonic permeability was developed. Since sucralose can survive the metabolic pathways of the gut microbiome, it is deemed as an excellent marker to use for measuring permeability in the colon. We have shown a proof of concept that using our chemical assay, sucralose can be measured with sensitivity in the range it is expected to appear in actual samples.