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Postoperative ileus (POI) is a frequent condition after abdominal surgery.POI causes suffering for patients and significant costs for the healthcare system.Several brain peptides are involved in the development of POI.Chewing gum may be an applicable method to alleviate symptoms of POI.Postoperative ileus (POI) develops after abdominal surgery irrespective of the site of surgery. When prolonged, POI can lead to longer hospitalization times and higher healthcare costs. Moreover, it is associated with complaints for the patient. In order to develop new strategies to treat this condition, a deeper understanding of the pathophysiology of the POI is necessary. This review will focus on brain peptides (ghrelin, nesfatin-1, somatostatin, corticotropin-releasing factor, thyrotropin-releasing hormone and calcitonin gene-related peptide) involved in the mediation of POI and the possible modulation of these pathways to shorten the time of POI. Lastly, the role of vagal signaling or chewing gum as potential treatment strategies of alleviating symptoms of POI is discussed.