lntestinal microenvironment, epithelial barrier interactions and human milk oligosaccharide supplementation in irritable bowel syndrome

Abstract: Alterations of the microbiota-host interactions at the mucosal border may be of importance in symptom generation in irritable bowel syndrome (IBS), a disorder of gut-brain interaction. Hence, microbiota-targeted interventions may benefit some patients by beneficially modulating the intestinal microenvironment. This thesis aimed to determine the importance of the intestinal microenvironment for the intestinal immune activity and barrier function in IBS, as well as to assess the effects of human milk oligosaccharide (HMO) supplementation in IBS patients. First, we describe that the IBS patients have a distinct intestinal microenvironment, in particular metabolites, that is linked to bowel habits. Second, we present an in vitro model using patient-derived fecal supernatants and healthy-derived epithelial colonoids for exploring the interactions between the intestinal microenvironment and the epithelial barrier in IBS. Third, we show that a HMO mixture of 2’-Ofucosyllactose and lacto-N-neotetraose (4:1 ratio) (2’FL/LNnT) increases the abundance of bifidobacteria, with no risk of symptom deterioration. Finally, we demonstrate that supplementation with 2’FL/LNnT modulates the gut microbiota, increasing bifidobacteria, and fecal and plasma metabolites, but it does not influence the intestinal immune activity and barrier function. In conclusion, the results of this thesis support the importance of the intestinal microenvironment and the microbiota-host interactions at the mucosal border in IBS, which might be modulated by HMO supplementation. Future studies are warranted to provide a better insight into the cross talk at the mucosal border as well as the mechanisms of action of HMO supplementation for the management of IBS symptoms.