Non-invasive measurement of intestinal barrier function in environmental enteropathy using transcutaneous fluorescence sensing

BackgroundUndernutrition represents a critical global health concern and is associated with a multifaceted breakdown in gut function - termed environmental enteropathy (EE) - which leads to increased intestinal permeability, inflammation and nutrient malabsorption. Current clinical approaches to assess intestinal permeability are costly, invasive, unreliable and/or difficult to perform in certain populations. ObjectivesWe used transcutaneous fluorescence spectroscopy (TFS) - a novel method for non-invasive assessment of gut function - to investigate intestinal barrier function in EE. DesignVolunteers were recruited in a Zambian community where EE is prevalent, and in the UK to undergo TFS measurements in a cross-sectional study. Data were compared between groups and were correlated with the lactulose:rhamnose (LR) test. ResultsTFS demonstrated significant differences in intestinal barrier function between UK and Zambian volunteers. Both peak fluorescence intensity (p=0.003) and area under fluorescence curves (p=0.02) were higher in Zambian than UK participants, suggesting increased permeation of TFS contrast agent. No differences were observed in time taken to reach peak, indicating no differences in factors affecting uptake rate (e.g. gastric emptying). Finally, fluorescence kinetics and regression analysis revealed strong correlations between TFS data and urinary recoveries of lactulose and rhamnose (Spearmans r [&ge;] 0.78; p < 0.002). ConclusionsTFS reveals population differences in permeability. It also allows simultaneous assessment of multiple elements of gut function (intestinal barrier integrity and gastric emptying) using a rapid, sample-free methodology. Combined with correlation to the LR test, this implies potential to advance studies of gut health and to improve clinical monitoring. KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABSUndernutrition represents a critical global health concern, accounting for nearly half of all deaths in children under the age of 5 and causing stunted physical and mental development in millions more. Importantly, undernutrition is hard to combat solely through provision of food as it is associated with a complex impairment in gut function known as environmental enteropathy (EE). A key facet of EE is so-called "leaky gut," an effect where a degraded gut barrier allows passage of harmful compounds from the gut into the blood stream. Leaky gut has been widely studied in EE but understanding of the role of gut function in undernutrition is still incomplete due to the limitations of existing tests to measure gut leakiness (which typically involve measuring the recovery of sugar molecules in urine). What this study addsIn this study, we used a new technology - transcutaneous fluorescence spectroscopy (TFS) - to study leaky gut in EE. TFS allows rapid, non-invasive assessment of gut leakiness by measuring the uptake of fluorescent molecules from the gut into the blood stream using a non-intrusive light sensor attached to the skin. Our results show that gut leakiness is higher in EE patients in Zambia than in healthy volunteers in the UK and that TFS results correlate with the lactulose:rhamnose (LR) test (an existing but much more cumbersome approach for measurement of gut leakiness). How this study might affect research, practice or policyOur results demonstrate that TFS can provide fast and non-invasive assessment of gut health in undernutrition settings. Due to its advantages over LR and other existing tests, this implies potential to allow more advanced study of EE and to improve clinical monitoring in the future.