Disturbance of the inflammatory response in the gut is important in several clinical diseases ranging from inflmmatory bowel disease to postoperative ileus. Several feedback mechanisms exist that control the inflammatory cascade and avoid collateral damage. In the gast rointestinal tract, it is of particular importance tocontrol the immune response to maintain the balance that allows dietary up take and utilization of nutrientson one hand, while preventing invasion of bacteria and toxins on the other hand. The process of digestion and absorption of nutrients requires a relative hyporesponsiveness of the immune cells in the gut to luminacontents which is not yet fully understood. Recentlythe autonomic nervous system has been identifi ed asan important pathway to control local and systemic inflammation and gut barrier integrity. Activation of thepathway is possible via electrical or via pharm acological interventions, but is also achieved in a physiologicamanner by ingestion of dietary lipids. Administration of dietary lipids has been shown to be very effectivein reducing the inflammatory cascade and maintaining intestinal barrier integrity in several experimental studies. This beneficial effect of nutrition on the inflammatory response and intestinal barrier integrity opens new therapeutic opportunities for treatment of certain gastrointestinal disorders. Furthermore, this neural feedback mechanism provides more insight in the relative hyporesponsiveness of the immune cells in the gut. Here, we will discuss the regulatory function of the autonomic nervous system on the inflammatory response and gut barrier function and the potential benefit in a clinical setting. Disturbance of the inflammatory response in the gut is important in several clinical diseases ranging from inflmmatory bowel disease to postoperative ileus. Several inflammatory mechanisms exist that control the inflammatory cascade and avoid collateral damage. In the gast rointestinal tract, it is of particular importance tocontrol the immune response to maintain the balance that allows dietary uptake and utilization of nutrientson one hand, while preventing invasion of bacteria and toxins on the other hand. The process of digestion and absorption of need requires a relative hyporesponsiveness of the immune cells in the gut to luminacontents which is not yet fully fully understood. Recently the autonomic nervous system has been identified as an important pathway to control local and systemic inflammation and gut barrier integrity. by ingestion of dietary l Administration of dietary lipids has been shown to be very effective in reducing the inflammatory cascade and holding intestinal barrier integrity in several experimental studies. This beneficial effect of nutrition on the inflammatory response and intestinal barrier integrity opens new therapeutic opportunities for treatment of certain gastrointestinal disorders ., This neural feedback mechanism provides more insight in the relative hyporesponsiveness of the immune cells in the gut. Here, we will discuss the regulatory function of the autonomic nervous system on the inflammatory response and gut barrier function and the potential benefit in a clinical setting.