Mechanistic Study of Coffee Effects on Gut Microbiota and Motility in Rats.

Consumption of coffee has benefits in postoperative ileus. We tested the hypothesis that the benefits may be related to the effects of coffee on gut microbiota and motility and studied the mechanisms of action in rats. The in vitro and in vivo effects of regular and decaffeinated (decaf) coffee on gut microbiota of the ileum and colon were determined by bacterial culture and quantitative RT-PCR. Ileal and colonic smooth muscle contractility was determined in a muscle bath. In the in vivo studies, coffee solution (1 g/kg) was administered by oral gavage daily for 3 days. Compared to regular LB agar, the growth of microbiota in the colon and ileal contents was significantly suppressed in LB agar containing coffee or decaf (1.5% or 3%). Treatment with coffee or decaf in vivo for 3 days suppressed gut microbiota but did not significantly affect gut motility or smooth muscle contractility. However, coffee or decaf dose-dependently caused ileal and colonic muscle contractions in vitro. A mechanistic study found that compound(s) other than caffeine contracted gut smooth muscle in a muscarinic receptor-dependent manner. In conclusion, coffee stimulates gut smooth muscle contractions via a muscarinic receptor-dependent mechanism and inhibits microbiota in a caffeine-independent manner.

An opioid receptor-independent mechanism underlies motility dysfunction and visceral hyperalgesia in opioid-induced bowel dysfunction.

Constipation and abdominal pain are commonly encountered in opioid-induced bowel dysfunction (OBD). The underlying mechanisms are incompletely understood, and treatments are not satisfactory. As patients with OBD often have fecal retention, we aimed to determine whether fecal retention plays a pathogenic role in the development of constipation and abdominal pain in OBD, and if so to investigate the mechanisms. A rodent model of OBD was established by daily morphine treatment at 10 mg/kg for 7 days. Bowel movements, colonic muscle contractility, visceromotor response to colorectal distention, and cell excitability of colon-projecting dorsal root ganglion neurons were determined in rats fed with normal pellet food, or with clear liquid diet. Morphine treatment (Mor) reduced fecal outputs starting on day 1, and caused fecal retention afterward. Compared with controls, Mor rats demonstrated suppressed muscle contractility, increased neuronal excitability, and visceral hypersensitivity. Expression of cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) was upregulated in the smooth muscle of the distended colon in Mor rats. However, prevention of fecal retention by feeding rats with clear liquid diet blocked upregulation of COX-2 and NGF, restored muscle contractility, and attenuated visceral hypersensitivity in Mor rats. Moreover, inhibition of COX-2 improved smooth muscle function and fecal outputs, whereas anti-NGF antibody administration attenuated visceral hypersensitivity in Mor rats. Morphine-induced fecal retention is an independent pathogenic factor for motility dysfunction and visceral hypersensitivity in rats with OBD. Liquid diet may have therapeutic potential for OBD by preventing fecal retention-induced mechanotranscription of COX-2 and NGF.NEW & NOTEWORTHY Our preclinical study shows that fecal retention is a pathogenic factor in opioid-induced bowel dysfunction, as prevention of fecal retention with liquid diet improved motility and attenuated visceral hyperalgesia in morphine-treated animals by blocking expression of cyclooxygenase-2 and nerve growth factor in the colon.