Su2072 The Bitter Taste Receptor Agonist Denatonium Benzoate Alters Intragastric Pressure Profiles During Nutrient Drink Test in Healthy Volunteers

Abstract

Background: Bitter taste receptors are expressed in the stomach and the duodenum but their function is unclear. We assessed the effects of a potent bitter tastant on intragastric pressure (IGP, a measure of gastric accommodation) and satiation in response to a liquid meal. Methods: We conducted a single-blind crossover trial of 16 healthy volunteers (8 female; mean age 30±2 yrs; mean BMI 23.8±0.9) given 1 μmol/kg (0.1mL/kg) of a 10mM denatonium benzoate (DB) solution or placebo in random order on separate occasions at least 1 week apart. First, both a standard high-resolution manometry (HRM) catheter and a 4mm feeding catheter were positioned intra-gastrically via the nose with location confirmed by detection of the lower esophageal sphincter (LES) and/or fluoroscopy. After an adjustment period, DB or placebo was administered through the feeding catheter. After 30 min, nutrient drink (ND; 30% fat, 42% carbohydrate, 28% protein) was infused into the stomach at 60mL/ min until maximum satiation, at which point it was stopped. Satiation (scored on 0-5 scale) was assessed every minute. IGP was measured as average pressure over 5 channels in the proximal stomach at least 1cm below the LES, with 5-minute baseline measured 10 minutes before ND start. Outcomes were compared with paired t-test or Wilcoxon test as appropriate. All data are expressed as mean ± SEM unless otherwise stated. Results: Baseline IGP prior to ND infusion was similar between DB and placebo (Table). After DB treatment, the nutrientinduced drop in IGP from baseline (baseline-nadir) was inhibited (p=0.056) and delayed (p=0.007) compared to placebo. The total area under the IGP curve during nutrient infusion was significantly smaller after DB (p=0.021), consistent with attenuation of the gastric accommodation response (Figure). Satiation score at nadir IGP tended to be higher after DB vs placebo (p=0.087). The volume of ND ingested and the duration of the nutrient infusion were not statistically different between groups. No adverse effects were noted after either agent. Conclusion: The potent bitter tastant DB inhibits gastric accommodation to a meal, independently of taste receptor stimulation in the tongue. Themechanism and receptors involved in this action warrant further study.