Irritable bowel syndrome (IBS) is a frequent disorder characterized by visceral pain without established biological markers. The low efficacy of the therapies often leads IBS patients to seek more effective pain killers such as opioids which misuse has becoming a public health problem. In this context, our data showing that enkephalin deficiency in immune cells results in the development of IBS-like symptoms including increased permeability, visceral pain and anxiety, arise the question whether a defect in the opioid tone may define IBS subgroup of patients. The project aims at deciphering the mechanism of this immune-derived opioid-mediated regulation of the intestinal homeostasis and the potential link with the development of patient IBS symptoms. Our project will give opportunities to better characterize IBS patients and/or to develop new therapeutic strategies including new peripheral-restricted opioid drugs to protect patients from centrally-mediated opioid side-effects.