However, the effects of dietary modification on mucosal inflammation, myenteric ganglionitis and intestinal motility are unknown and subject for further research. In keeping with the hypothesis of a luminal contributing factor in human FGID, fecal supernatants of patients. Some groups have advocated a role for gluten as a luminal contributor in IBS, although this was challenged by others. In a randomized controlled trial in non-celiac IBS patients, a glutencontaining diet was associated with significantly VE-822 higher small intestinal permeability and altered expression of tight junction proteins in comparison to a gluten-free diet, especially in individuals who were HLA-DQ2/8 positive. Finally, in ob/ ob mice, increased intestinal permeability was reported which was dependent on the gut microbiota and could be reversed by treatment with prebiotics. Together, the available data suggest a luminal, possibly food-related, factor in intestinal hyperpermeability, both in IBS patients and the BB-rat. Further studies to identify the triggering food constituents or other players like proteases and bacteria are awaited. The intestinal immune activation in the BB-rat was characterized by infiltration of PMN cells and increased MPO-activity. The full characterization of the inflammatory infiltrate was beyond the scope of the current study. Histologically, PMN cells in our study may encompass neutrophils, eosinophils and mast cells. However, the combination with increased MPO activity suggests a predominantly neutrophilic infiltrate. Although most studies have focused on the increased presence of eosinophils, mast cells and lymphocytes in FGID, neutrophils have been reported as well. We acknowledge that also monocytes and classically activated macrophages are known to express MPO, but the absence of significant iNOS upregulation in young rats arguments against macrophages as an important player in the early inflammatory phase, although they do seem to participate in the older rats as demonstrated by iNOS overexpression after 110 days of age. Although at this point we cannot exclude or confirm the presence of mast cells and eosinophils in our model, since they are not easily discernible on H&E staining in rodents, we have observed only few lymphocytes. The absence of a major lymphocytic infiltration is probably related to the lymphopenic nature of the model due to the mutation of the Gimap5 or lyp gene. An intriguing observation was that only around 50% of the animals developed a transmural inflammatory reaction and loss of nitrergic neurons, even though they were litter mates, sharing the same environment, chow and genetics. We were not able to identify subgroups in the younger age group, suggesting that the early hyperpermeability is a general, strain-specific defect, while transmural inflammation and the secondary permeability defect depend on additional, unknown factors.