Novel mechanisms of nutrient induced symptoms in common gastrointestinal disorders

Irritable bowel syndrome (IBS) is a frequent gastrointestinal disorder characterized by abdominal pain associated to bowel movements or to changes in stool habits. The pathophysiology of IBS is still not fully understood. Many patients experience an increase in symptom severity following nutrient ingestion, although mechanisms underlying this observation are unclear. Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) are known to induce symptoms in patients with IBS. In an ongoing study, our group has shown a highly individualized pattern of specific FODMAPs inducing symptoms in patients. The reason for this remains unclear as the proposed mechanisms through which FODMAPs induce symptoms (i.e. osmotic and fermentation effects) do not explain an individualized symptom response.  Recently, in vivo confocal laser endomicroscopy (CLE) has shown acute microscopical changes in the duodenum of IBS patients upon exposure to specific foods. The observed reactions suggest an acute capillary leak and enhanced duodenal permeability following nutrient exposure, possibly reflecting a local allergic response. Similarly to the pattern above, patients reacted in an individualized manner to specific nutrients. This project aims to further elucidate the mechanisms underlying the individual nutrient induced symptoms in patients with IBS. 1) we aim to further shed light on the mechanisms underlying symptom generation upon FODMAP exposure using radiologic imaging and measurement of gut peptides following exposure of specific FODMAPs. We speculate that rather than solely osmotic and fermentation effects, changes in gut-peptide secretion may explain in part the individualized reaction to specific FODMAPs. 2) Mast cells might play a key role in the acute reaction to nutrients observed in the duodenum. Due to the submucosal localisation of mast cells , we hypothesize that an altered duodenal permeability is a prerequisite for nutrient sensitization and for acute mast cell mediated reactions upon exposure and thus for the observed reactions in CLE. In summary, this project aims to further shed light on the mechanisms underlying individual nutrient induced symptoms in IBS assessing mechanisms underlying two nutrient groups previously described to induce symptoms in IBS.