Challenge models and biomarkers of human intestinal barrier function

Sammanfattning: The intestinal barrier is an essential component in maintaining human health, and several diseases and disorders have been associated with a disrupted intestinal barrier function. To evaluate the efficacy of different interventions intended to strengthen intestinal barrier function, there is a need for both appropriate challenge models as well as easily accessible biomarkers. The overall aim of this thesis was to explore new challenge models of human gut barrier as well as to investigate potential biomarkers to assess its function. Paper I shows that a sauna-induced dehydration protocol increased intestinal permeability without causing major damage to the intestinal barrier, suggesting it as a potential challenge model of the gut barrier. Paper II shows that the acute intense psychological stress generated by skydiving did not affect intestinal permeability, indicating that gut barrier disruption likely requires sustained psychological stress. Paper III describes the systemic effect of an established strenuous exercise challenge on various biomarkers of gut barrier and immune function, as well as their correlations. Paper IV used a cohort of patients with diarrhoea-predominant irritable bowel syndrome (IBS-D) to show how several biomarkers linked to increased permeability correlated with other markers associated with IBS-D. All papers also explored potential surrogate permeability markers for the urinary excretion ratio of lactulose and rhamnose which is a common in vivo method for measuring small intestinal permeability. In conclusion, this thesis provides insights into different challenge models of the human intestinal barrier function and addresses important considerations about the application of currently used biomarkers for its assessment.