This insight into HSP70-mediated NK cell activation may lead to the development of new therapeutic approaches that use NK cells to target cancer or virus-infected cells. Functional gastrointestinal disorders like irritable bowel syndrome and functional dyspepsia are characterized by bothersome gastrointestinal complaints in the absence of an underlying organic cause that readily explains the symptoms. Despite the high prevalence, the pathophysiology of FGID remains incompletely understood and the current XAV939 treatment options are limited and have suboptimal efficacy. Impaired intestinal barrier function, low-grade immune activation, and altered neuronal control of gastrointestinal motility, have been suggested to be involved in the pathogenesis. An attractive and often-cited disease model for FGID, and also for chronic inflammatory bowel disease, is based on luminal antigen penetration through an impaired intestinal barrier leading to immune activation in the intestinal wall. On the other hand, it is well recognized that increased intestinal permeability may also be a consequence of inflammatory changes. The current data on intestinal permeability in human intestinal disorders are mainly associative, with a possible exception of Crohn’s disease, and celiac disease. Especially in FGID, a causeconsequence relationship between the observed alterations in permeability, immune activation and motility disturbances, has not been established so far and is subject of ongoing debate. The distinction is relevant since therapeutic interventions aimed at restoring barrier function could represent a novel treatment approach to several gastrointestinal disorders. A spontaneous animal model sharing key intestinal characteristics of human FGID would be instrumental to separate cause from consequence and to study future treatments. The BioBreeding rat is a well-established animal model for type 1 diabetes. The BB-rat consists of two strains, the diabetesresistant and the diabetes-prone strain. Hyperglycemia develops in 50–95% of the BB-DP animals depending on the substrain, diet and housing conditions. The hyperglycemic BB-DP rat displays increased intestinal permeability prior to the development of diabetes, mucosal and neuromuscular inflammation and loss of nitrergic motor neuron function. We have previously reported that the development of the inflammatory enteropathy and loss of nitrergic neurons in the BB-rat also occur in BB-DP animals which do not develop diabetes. These features potentially identify the normoglycemic BB-DP rat as a suitable animal model for inflammatory neuromuscular dysfunction. However, current data on intestinal permeability and functional neuromuscular data are limited to diabetic animals, in which diabetes potentially is a confounding factor. Moreover, it is unclear how permeability, inflammation and intestinal nitrergic neuropathy.