Mechanisms Underlying the Benefits of Coffee in Postoperative Ileus

Background and Aims: Postoperative ileus (POI) is a motility dysfunction associated with inflammation in the gastrointestinal (GI) tract after abdominal surgery. Management relies on supportive care, as there is no effective medical treatment. Clinical trials found that coffee consumption improves bowel movement and shortens hospital stays in POI. We aimed to investigate the mechanisms underlying the beneficial effect of coffee in an animal model of POI. Methods: Mouse POI was established by manipulation of the small intestine with wet swab applicators for 5 min. Mice were then treated with water, regular or decaffeinated coffee (10 mg per day) by oral gavage and euthanized 24 h after the operation. Key Results: Intestinal manipulation slowed GI transit rate from 5.64 ± 0.47 to 3.77 ± 0.16 (N = 6, measured by geometric center), reduced intestinal muscle contractility, and induced an acute inflammatory response with increased expression of proinflammatory mediators such as IL-6, IL-1, CCL2, and CXCL-1 in the POI intestine. Coffee treatment (regular or decaffeinated) did not reduce inflammation or the expression of inflammatory mediators but significantly improved muscle contractility and increased GI transit to 4.59 ± 0.31 (N = 5) and 4.80 ± 0.29 (N = 5) in POI mice (regular and decaffeinated coffee, respectively). Regular or decaffeinated coffee dose-dependently (0.1–10 mg/mL) increased contractility of intestinal muscle strips. The contractile effect was not affected by neural toxin tetrodotoxin (10−6 M) or cholinergic nicotinic antagonist hexamethonium (10−4 M) but was completely abolished by muscarinic receptor antagonist atropine (10−6 M). Conclusions: Coffee consumption does not attenuate inflammatory response but improves GI motor function and stimulates intestinal smooth muscle contractions in the mouse model of POI. Coffee stimulates contractions in a caffeine-independent manner through a cholinergic muscarinic receptor-dependent mechanism.