Recto-colonic reflex is impaired in patients with irritable bowel syndrome

Motor and sensory dysfunction of the gut are present in a subset of patients with irritable bowel syndrome (IBS). Recent studies have demonstrated the presence of a recto-colonic inhibitory reflex in healthy humans. It is not known whether this reflex exists in IBS. We studied rectal compliance, perception and the recto-colonic reflex by measuring volume responses of the descending colon to rectal distentions by barostat in 26 IBS patients and 13 healthy controls under both fasting and postprandial conditions. In the fasting state, rectal distention inhibited colonic tone and phasic motility to a similar extent in health and IBS. After a meal, rectal distention inhibited colonic tone and phasic motility to a lesser degree (P < 0.05) in IBS than health. Under postprandial but not fasting conditions, rectal distentions of increasing intensity were associated with higher pain scores in IBS than in health. Rectal distention inhibits tonic and phasic motility of the descending colon in healthy controls and in IBS patients. Postprandially this recto-colonic inhibitory reflex is impaired and attenuated in IBS patients compared with controls. These findings point to an altered reflex function in IBS and have implications for pathophysiology and therapy.     

A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia

Abstract  Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z-338) was well-tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double-blind, placebo-controlled study (14, 21 and 28 days, respectively, for run-in, study drug administration and follow-up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and ¹³C breath test, symptoms by daily diary cards and QOL by SF-36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation ( P  = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating ( P  = 0.001) and overall symptom score ( P  = 0.022), and at week 3 for bloating ( P  = 0.008) and heartburn ( P  = 0.041). 100 mg was also better than placebo for QOL (physical function) ( P  = 0.003). Acotiamide was safe and well-tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated.     

Intragastric acidification inhibits motilin-induced phase III activity in humans

In a randomized, placebo-controlled crossover design we studied the effect of gastric acidification on motilin-induced interdigestive antropyloroduodenal motility. Ten healthy volunteers participated in the study consisting of four experiments. Each experiment started after a spontaneous occurring phase III and consisted of intragastric infusion of either saline or acid (0.08 mol L(-1) HCl) for 90 min and intravenous infusion of either saline or motilin (4 pmol kg(-1) min(-1)) for 30 min. Antropyloroduodenal motility and pH were recorded continuously for 240 min. Reoccurrence of phase III was significantly (P < 0.05) earlier during intragastric saline-intravenous motilin infusion compared with control (intragastric saline-intravenous saline), 52 min (range 25-79) and 113 min (84-141) respectively. This effect was completely abolished during intragastric acid-intravenous motilin infusion, 112 min (82-142). The percentage of phase III of antral origin was significantly (P < 0.05) higher during intragastric saline-intravenous motilin infusion (90%) compared with control (30%). The mean area under the contraction (AUC) for phase II was significantly (P < 0.05) lower during intragastric saline-intravenous motilin infusion and intragastric acid-intravenous saline infusion compared with control. It is concluded that in humans intragastric acidification inhibits the effect of motilin on antroduodenal motility, decreases the AUC of antral phase II contractions and delays the occurrence of phase III of the migrating motor complex.     

Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function

Abstract  Tryptophan is the precursor of a wide array of metabolites, which are involved in a variety of aspects of human nutrition and metabolism. Accumulating evidence suggests a role of tryptophan metabolites, especially serotonin (5-hydroxytryptamin) in intestinal (patho) physiology, although mechanisms of action are still poorly understood. Alterations of serotonin metabolism may give rise to gastrointestinal dysfunction. Recently, it has been postulated that other metabolites of tryptophan, mostly of the kynurenine pathway, also play a role in regulating gut function. This review analyses the current knowledge of the interrelationship between tryptophan metabolic pathways and summarizes the existing scientific evidence regarding the role of tryptophan metabolites in intestinal function and in the pathogenesis of gastrointestinal diseases.