Su2072

The Bitter Taste Receptor Agonist Denatonium Benzoate Alters IntragastricPressure Profiles During Nutrient Drink Test in Healthy VolunteersChristopher N. Andrews, Sofie Verschueren, Pieter Janssen, Anne Maes, Eveline Deloose,Inge Depoortere, Jan F. Tack

Background: Bitter taste receptors are expressed in the stomach and the duodenum buttheir function is unclear. We assessed the effects of a potent bitter tastant on intragastricpressure (IGP, a measure of gastric accommodation) and satiation in response to a liquidmeal. Methods: We conducted a single-blind crossover trial of 16 healthy volunteers (8female; mean age 30±2 yrs; mean BMI 23.8±0.9) given 1 μmol/kg (0.1mL/kg) of a 10mMdenatonium benzoate (DB) solution or placebo in random order on separate occasions atleast 1 week apart. First, both a standard high-resolution manometry (HRM) catheter anda 4mm feeding catheter were positioned intra-gastrically via the nose with location confirmedby detection of the lower esophageal sphincter (LES) and/or fluoroscopy. After an adjustmentperiod, DB or placebo was administered through the feeding catheter. After 30 min, nutrientdrink (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 theproximal stomach at least 1cm below the LES, with 5-minute baseline measured 10 minutesbefore 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 priorto ND infusion was similar between DB and placebo (Table). After DB treatment, the nutrient-induced 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 infusionwas significantly smaller after DB (p=0.021), consistent with attenuation of the gastricaccommodation response (Figure). Satiation score at nadir IGP tended to be higher afterDB vs placebo (p=0.087). The volume of ND ingested and the duration of the nutrientinfusion were not statistically different between groups. No adverse effects were noted aftereither agent. Conclusion: The potent bitter tastant DB inhibits gastric accommodation to ameal, independently of taste receptor stimulation in the tongue. Themechanism and receptorsinvolved in this action warrant further study.

Su2073

Lactose Intolerance in Chinese Patients With Functional Bowel DiseaseLiang Luo, Yanyong Deng, Hua Chu, Jianfeng Yang, Yanqin Long, Xia Zheng, ZhihuiHuang, Yubin Zhu, Huiqin He, Michael Fried, Ning Dai, Mark R. Fox

Background: Accumulating evidence indicates a high prevalence of lactose intolerance (LI)in patients with functional bowel disease (FBD) such as irritable bowel syndrome (IBS).However, the underlying factors that determine the risk of LI in this group and whethercertain FBD symptoms are more common in patients with LI remains uncertain. Methods:880 consecutive patients seen for assessment of functional bowel symptoms were recruitedfrom a single University Hospital in Southeastern China, and 64 healthy volunteers wererecruited through public advertisement. All patients were randomly assigned a lactose hydro-gen breath test (LHBT) of lactose dose of 10g, 20g, or 40g, with the measurement of hydrogenproduction and LI symptom scores. A questionnaire containing Rome III criteria, hospital

S-549 AGA Abstracts

anxiety and depression scale (HADs) and general personal information was completed.Results: Among the 880 patients (44±12 yr, 44% female) and 64 healthy volunteers (41±15yr, 48% female) studied, the prevalence of lactose intolerance was 59.9% (n=527) and 28.1%(n=18) respectively. The prevalence of LI was higher in patients with functional bowelsymptoms (P,0.0001). Further, the prevalence of LI in the patients increased with LHBTdose: 10g LHBT of prevalence (n=51, 18%), 20g (n=285, 58%), 40g (n=263, 71%). Patientswith LI were slightly younger than non-LI (43±12 vs. 45±12 yr, P=0.009) The proportionof patients with LI increased with the educational level (P=0.04), while other factors suchas gender, occupation, life event score, depression or anxiety status were not differentbetween the LI and non-LI patients. Compared with non-LI patients, LI patients more oftenreported bowel movement less than 3 times per week (P=0.007) and straining during bowelmovement (P=0.044). The frequency of other FBD symptoms and the severity of overallsymptoms (P=0.228) was similar in both LI and non-LI groups. 785 patients were confirmedas FBD, and the remaining 95 patients did not meet the diagnostic criteria for symptomduration. Of the former group, 475 (54.0%) were IBS, 165 (18.8%) functional diarrhea, 75(8.5%) functional constipation, 46 (5.2%) functional bloating, and 24 (2.7%) undefinedFBD. The prevalence of functional disease or each FBD subtype was not significantly differentbetween LI and non-LI patients. Conclusions: Our study showed that the lactose intolerancewas commoner in Chinese patients with functional bowel disease than healthy subjects.Young age and high educational level were associated with LI development in FBD patients.FBD patients who were lactose intolerant more frequently reported constipation; howeverthe frequency and severity of other symptoms was not affected.General characteristics and LI associated factors of patients with functional bowel symptom

FBD symptoms in LI patients

Su2074

Gastrointestinal (GI) Symptoms Induced by Spicy, Sour, and Fatty FoodIngestion in Functional Dyspepsia (FD): A Difference Between Epigastric PainSyndrome (EPS) and Postprandial Distress Syndrome (PDS)Tanisa Patcharatrakul, Prima Singhagowinta, Pinit Kullavanijaya, Sutep Gonlachanvit

Spicy, sour, and fatty foods often aggravate gastrointestinal symptoms in patients with FD.Whether there is different symptom response to these specific foods between EPS and PDShas not been well explored. Methods: 283 consecutive dyspeptic patients (191F, age46±15yr)who had normal upper endoscopy were interviewed regarding frequency and severity ofeach upper and lower GI symptoms and history of GI symptoms induced by spicy, fatty orsour foods. Patients were classified as epigastric pain syndrome (EPS)(n=127), postprandialdistress syndrome (PDS)(n=60) and mixed EPS-PDS(n=96) using the symptoms profilesdescribed in the Rome III criteria. Patients with overlapping FD with other functional GIdisorder were excluded. The data from FD patients were compared with 100 asymptomatichealthy volunteers (HV)(65F, age41±7yr). Results: 195 of the 283(69%) FD patients hadGI symptoms induced by at least one of the 3 foods (spicy, fatty or sour) ingestion. Thisprevalence was higher than HV (n=12/100)( p ,0.001). There was higher prevalence ofspicy and sour foods induced GI symptoms in EPS and EPS+PDS patients than PDS patients(p,0.05) (see table). In contrast, there was higher prevalence of fatty foods induced GIsymptoms in PDS than EPS and EPS+PDS (p,0.05). The most common symptoms inducedby spicy foods were epigastric burning and/or pain which developed in 76 of 80 EPS, 21of 28 PDS and 67 of 70 mixed EPS+PDS patients who had GI symptom(s) induced by spicyfoods. 12 HV developed GI symptom after spicy foods and 9 of these 12 volunteers developedepigastric burning/pain. 98(35%) FD patients had GI symptoms after sour foods. Epigastricburning/pain were also the most common symptoms induced by sour foods in FD. Thesesymptoms were developed in 35 of 38 EPS, 10 of 15PDS, and 42 of 45 EPS+PDS patientswho had GI symptom(s) induced by sour foods. Only one HV developed symptom fromboth spicy and sour food which was diarrhea. 48(17%) FD patients had GI symptomsinduced by fatty foods ingestion. Postprandial fullness was the most common symptominduced by fatty foods which developed in 12 of 16 EPS, 15 of 18 PDS, and 10 of 14 ofmixed EPS-PDS patients who had GI symptom(s) induced by fatty foods, while HV had noGI symptom induced by fatty foods. Conclusions: Hypersensitivity to fatty, spicy and sourfoods is present in FD. Spicy and sour foods ingestion induced mainly epigastric burning orpain, especially in EPS. Whereas, fatty foods induced mainly postprandial fullness symptoms,especially in PDS. This study suggests that EPS and PDS are 2 distinct GI conditions andthey may need different dietary recommendation.

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Su2075

Patients With IBS Have Lower Intake of Fodmaps Compared With the GeneralPopulationTherese M. Liljebo, Lena Böhn, Hans Törnblom, Magnus Simren, Stine Störsrud

Background: It has been suggested that a diet low in fermentable short chain carbohydrates,FODMAPs (Fermentable Oligo-Di-Monosaccharides and Polyols) can reduce gastrointestinalsymptoms in patients with irritable bowel syndrome (IBS) (Gibson & Shepherd Am JGastroenterol 2012). However, the intake of FODMAPs in IBS patients compared to thegeneral population has not been studied. Aim: To measure the intake of FODMAPs inpatients with IBS in comparison with the general population, and to determine the majorsources of FODMAPs in the diet of IBS patients. Method: We included 115 patients withIBS according to the Rome III criteria (39.1±13.0 (mean± SD) years; 88 females) referredto our outpatient clinic. They completed a 4-days food registration record, which wascompared with 115 age-and gender matched control subjects from a nation-wide dietarysurvey. A database including content of fructose, fructan, lactose, galacto-oligosaccharides(GOS) and polyols in 1700 food items was developed specifically for this study to determinethe intake of FODMAPs. Results:The IBS patients had significantly lower intake of FODMAPsthan the control group from the general population (30.91±14.3 vs.34.56±12.67 g/day;p,0.05). The intake of lactose was lower in IBS patients compared to controls (10.47±8.22)vs.13.70±8.29 g/day; p, 0.001), while polyol intake was significantly higher in the IBS group(1.70±1.87 vs.1.25±1.64 g/day; p,0.05). However, there were no statistically significantdifferences regarding the intake of fructose (14.18±7.63 vs.15.28±6.93 g/day; p=0.24) fructan(3.91±1.73 vs.3.78±1.67g/day; p=0.55) or GOS (0.63±0.61vs. 0.53±0.56 g/day; p=0.16)between IBS patients and control subjects. The major food sources with naturally occurringfructan and contributing to the intake of fructan in both groups were onion, garlic, wheatand rye. Fruit drinks/-juices and apples were the main contributors to the fructose intake.The richest sources of polyols in the IBS group were pears and sugar-free sweets and in thecontrols pears, apples and sugar-free sweets. Legumes and wheat-products were the majorcontributors to intake of GOS in both groups. IBS patients ate less dairy products andreplaced 15% of lactose containing products with lactose-free, soy or oat products. Thepatients ingested half the amount of fruit drinks in comparison to the control group, andtheir intake of wheat containing food items was also lower than for the control group. Intakeof legumes and onions were equal in both groups except for garlic that was more frequentlyconsumed in the IBS group. Conclusion: Intake of FODMAPs seems to be lower in IBSpatients than in the general population, and this was mainly explained by a reduction ofthe intake of lactose containing food items. Further studies assessing the role of intake ofFODMAPs for symptoms in IBS patients are needed.

Su2076

Weight Regain After Roux-en-Y Gastric Bypass Surgery Is Associated WithDysphagia Symptoms but Not Manometric FindingsAna C. Tuyama, Shikha Mangla, Wai-Kit Lo, Walter W. Chan, Robert Burakoff,Christopher C. Thompson

Background: Roux-en-Y gastric bypass (RYGB) is an effective bariatric surgery for weightloss in obese patients. Prior studies indicated that 20% of bariatric patients experience weightregain (WR), which can lead to significant morbidity and metabolic complications. Thecause of WR may be multifactorial, and the underlying mechanisms have not been clearlyelucidated. Up to 30% of RYGB patients complain of dysphagia after surgery and may havedifficulty with solid foods. Based on our observations, these patients often adapt by consuminghigh caloric liquid diets, which can lead to significant weight gain. We hypothesize thatpost-RYGB dysphagia and esophageal dysmotility may play a role in WR by increasingconsumption of high-caloric liquids. Aim: To investigate the association between WR inpost-RYGB patients and their swallowing symptoms and esophageal motility profile on high-resolution manometry (HRM). Methods: Retrospective cohort study of post-RYGB patientswho underwent HRM at a tertiary care center in 6/2007-5/2012. Patients with underlyingesophageal motility disorders pre-RYGB, HRM performed , 2 months after RYGB, or needfor parenteral or tube feeding were excluded. WR was defined as a weight increase of ≥15%of maximal weight loss after RYGB. Demographic information, co-morbidities, and clinicalsymptoms were obtained from patient records. Esophageal motor characteristics (basal andresidual lower esophageal sphincter pressure, and esophageal body peristalsis and contractionamplitude) were extracted from HRM. Fisher-exact or chi-sqaured test for binary variablesand student's t-test for continuous variables were used to assess for differences between WRand non-WR groups. Multivariate analysis was performed using forward stepwise logisticregression. Results: 60 patients met inclusion criteria (age 50.0±11.2 yrs, 95% F). 35(58.3%) subjects experienced WR (age 50.6±9.7 yrs, 97.2% F), while 24 (40%) had at leastone abnormal parameter on HRM (36.1% WR vs 45.8% non-WR patients, p=0.45). Onunivariate analysis, dysphagia was significantly associated with WR (44.4% vs 12.5%, p=0.01). No specific esophageal motor profiles on HRM or other clinical symptoms correlatedwith WR. On multivariate analysis, dysphagia remained independently associated with WR

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(OR=5.6 p= 0.01). The c-statistic of the ROC curve for the prediction model was 0.66.Conclusions: Dysphagia was significantly associated with WR post-RYGB regardless of HRMfindings. No specific esophageal motility abnormality was predictive of WR. The majorityof post-RYGB patients with dysphagia had normal HRM findings, suggesting a functionalcause or sensory disturbance. RYGB may affect the afferent sensory innervation to theesophagus leading to dysphagia symptoms. Further studies are needed to further delineatethe pathophysiology of post-RYGB dysphagia and its relationship with WR.

Su2077

Body Weight in Patients With Gastroparesis: Roles of Symptoms, CaloricIntake, Physical Activity, and Body MetabolismCarol J. Homko, Linda C. Zamora, Guenther H. Boden, Henry P. Parkman

The range of body weights in patients with gastroparesis is variable. Despite chronic symp-toms, in addition to underweight patients, overweight and obese patients are seen. The aimof this study was to explore the relationships between symptoms, caloric intake, physicalactivity and energy expenditure with BMI in individuals with idiopathic gastroparesis andhealthy controls. This extended study builds upon data reported last year. Methods: 25healthy controls (C) and 21 subjects with idiopathic gastroparesis (GP) with delayed gastricemptying scintigraphy participated. Resting energy expenditure (REE) was measured byopen circuit indirect calorimetry using a ventilated hood system (TrueOne 2400 MetabolicMeasurement System). Body composition was assessed using bioelectrical impedance analysis(RJL Systems). Dietary intake was assessed using the Block Food Frequency Questionnaire.Gastroparetic symptoms were assessed with Patient Assessment of Upper GI Symptoms(PAGI-SYM). Physical activity was captured using the Paffenbarger exercise survey. Results:GP subjects were older than controls (43±15 vs 33±13 years; p=0.004), but BMI (26.6±5.5vs 25.2±7.6 kg/m2) and body fat (31.7±8.3 vs 27.1±9.4%) were similar. As expected,Gastroparesis Cardinal Symptom Index (GCSI) scores were higher in GP subjects than incontrols (15.8±6.8 vs 2.8±3.1; p,0.001). Mean caloric intake was lower in the GP group(1312±434 vs 1950±807 kcal; p,0.03). GP consumed less fat (44±16 vs 80 ±36 g; p,0.001),fiber (12±6 vs 21±9 g; p, 0.001), protein (46±21 vs 72±33 g; p ,0.01), but similarcarbohydrates (188±68 vs 235±97 g) than controls. Median calories expended per week foractivity were higher in controls (6,860 vs 644 kcal; p=0.004). REE did not differ betweenthe two groups (GP=1425±290 vs C=1479±242 kcal). Of the 21 GP patients, 12 patientshad lost weight or remained weight neutral (LW) and 9 had gained weight (GW) since theirdiagnosis of gastroparesis. There were no differences in age, disease duration (6.0±5.6 vs5.1±3.4 years) between GW and LW patients. GCSI scores were lower in GW subjects(12.7±5.2 vs 18.6±6.9; p,0.05) as well as in the nausea and vomiting (3.3±2.6 vs 6.3±3.0;p,0.05) and GERD (1.9±2.5 vs 9.2±8.6; p,0.03) subscales. GW subjects tended to consumemore calories (1481±556 vs 1200±307 kcal; p=0.2) and expend less calories for activity perweek (420 vs 826 median kcal; p=0.1) compared to GW subjects. Conclusions: As a group,GP patients consume less calories and expend less calories per week for activity, but havesimilar basal metabolic rates compared to control subjects. GP patients who gain weighthave less symptom severity, ingestmore calories, and have reduced physical activity comparedto GP patients who do not gain weight. Thus, symptom severity, caloric intake and levelof physical activity impact on the body weight of patients with gastroparesis.

Su2078

MicroRNA-Mediated Posttranscriptional Regulation At the Synapses in RostralCingulate Cortex Following Esophageal Acid Exposure in RatsBanani Banerjee, Bidyut K. Medda, Soumya Pochiraju, Jyoti N. Sengupta, Reza Shaker

Unique feature of brain neuronal system is its ability to regulate mRNA translation locallyat the synapses. MicroRNA (miRNA)-mediated local control of mRNA translation in synapsesaccounts for the long-lasting alteration in synaptic structure and function. Involvement ofthis regulatory mechanism in esophageal acid-induced sensitization has not been studied.AIMS: i) to isolate and characterize the synaptoneurosomes (SYN) from rostral cingulatecortex (rCC), the region involved in esophageal acid-induced cortical sensitization, ii) toidentify subset of miRNAs that are differentially expressed in synapses following esophagealacid infusion, iii) to identify miRNA target mRNAs that are relevant to synaptic plasticity.METHODS: Two groups of adult rats (SD, n=9/group) were used. Rats received 2ml ofeither 0.1N HCl or saline for 20 min at 0.1ml/min for 7 consecutive days under isoflurane(1% vol). Brains were removed under urathane 4 hours after the last acid infusion and slicedsagitally 2mm from midline. Cingulate cortices obtained from the first slice from either sideof the hemisphere were divided rostro-caudally and rCCs were collected. SYNs were isolatedfrom rCCs using density gradient ultracentrifugation. SYN preparation is highly enrichedin synaptic membranes, local protein synthesis machinery and miRNAs. Total RNA andprotein were extracted from the isolated SYN and whole rCC tissue (WT) and evaluated forthe expression of several synapse-relevant miRNAs and mRNAs using Taqman microRNAassays and quantitative RT-PCR respectively. The expression profile of Dicer 1 (maturemiRNA synthesizing enzyme) and rRNA (ribosomal RNA) was evaluated. Six synapse-relevant miRNAs including miR-124a, -92b, -181a, -26a, -323, and -494 were examinedand compared in SYN and WT from both groups. U87 expression was considered as internalcontrol. RESULTS: Significant upregulation of Dicer 1 in SYN was observed in acid-treatedgroup compared to saline-treated controls (p,0.01), whereas, no significant difference inexpression was observed between the groups in WT extracts. All 6 miRNAs exhibitedenrichment (.10 fold) in SYN compared to WT extracts and 4 of them (-181a, -92b, -26aand -323) were significantly upregulated in SYN from acid-treated group compared to saline-treated controls (p,0.05). WT extract didn't show any difference in expressions of miRNAsbetween acid and saline-treated animals. In western blots, AMPA receptor subunit, GluA2(miR-181a target) and CaMKIIα (miR-26a target) exhibited a significant downregulation inSYN from acid-treated group compared to saline-treated controls (p,0.05). CONCLUSIONS:Esophageal acid exposure results in miRNA-mediated posttranscriptional regulation locallyat the synapses in rCC. This mechanism may have a potential implication for better under-standing and treatment of acid-induced esophageal hypersensitivity.