The correlation between gastrointestinal symptoms and ASD is well established. Oxytocin (OT) and oxytocin receptor (OTR) abnormalities have also been documented in ASD. Oxytocin (OT) is a hormone that is found in breast milk and is expressed by enteric neurons. We discovered the expression and developmental regulation of OTR in the enteric nervous system and gastrointestinal epithelium. We also showed that combined administration of secretin and OT inhibits chronic colitis and associated activation of forebrain neurons. In this work, we are further elucidating the roles of OT and its receptor (OTR) in gut function generally, and in mucosal barrier function specifically. By comparing OTRnull (OTR knock-out) mice with wild-type mice, we are testing the hypothesis that OT/OTR signaling provides protection to the bowel and enteric neurons. If correct, this could provide a link between OTR gene polymorphisms in autistic patients and abnormalities in their gut function. The exciting aspect of this work is that the elucidation of the mechanism by which OT and OTR signaling is mucosal- and neuro-protective could lead to a better understanding of the developmental role of OT/OTR and its possible protective effects against adverse behavioral and physiological outcomes in ASD patients, especially high-risk infants, such as preterm infants.