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swaking in the severe slow transit group may reflect impaired neural responsiveness. Increasesin sleep duration in patients with slow transit raise the possibility of activity effects on colonpropulsion. Unlike other colon responses, IBS has little effect on sleep suppression of thecolon. These analyses provide rigorous quantification of sleep effects on colon activity inhealth vs. motor and functional disorders and form a foundation for studying nocturnalcolon responses in those who work rotating shifts or report sleep disturbances.

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Breath Methane in Functional Constipation: Changes During FermentableFiber TreatmentAntonia Perelló, Ana-Belen Vega, Lourdes Martos, García Montserrat, Immaculada García-Bayo, Victoria Andreu, Nadia Chahri, Agueda Abad, Mercè Barenys

INTRODUCTION: Bacterial colonic fermentation produces hydrogen (H2) in all subjectsand methane (CH4) only in subjects having methanogenic flora (30-60%). Both gases arebe measured in the lactulose breath test (LBT). The presence and degree of CH4 in LBT it'sbeen associated to constipation-subtype in IBS patients and to a slower intestinal transittime. We hypothesized that CH4 status and degree of production during treatment, couldinfluence the therapeutic response to fermentable fiber in functional constipation. AIMSAND METHODS: Our aim was to quantify the rate of subjects producing CH4 (M+) andto investigate H2 and CH4 production in breath testing before and during treatment offunctional constipation with a fermentable fiber (Ispaghula Husk 3,5 gr tid, during 4 weeks)and to relate it to the clinical response (based on a diary) and changes in transit colonictime. Functional constipation or constipated irritable bowel syndrome patients (fulfillingRome III criteria), duration for more than 1 year, seen in the primary care centres of oursanitary area were invited to enter the study. Patients filled a one-week diary to registratecomplete bowel movements, feeling of abdominal discomfort and bloating; underwent anstandardized LBT for H2 and Ch4 measurements; a dietary-fibre questionnaire and transittime measurement with radio-opaque markers. These variables were repeated after 4-5 week'streatment. To quantify overall gas production, an area under the curve (AUC) of LBT wascalculated for each H2 and CH4. We also recruited healthy volunteers as controls for basalmeasurements. A subject was considered to be M+ when basal methane was above 4 ppm.RESULTS: Forty-six constipated patients (3 men; 22 IBS-constipated) and 16 HV (1 man)were included. Mean age: 44,6±14 in patients vs 42,6±14 in HV (p=ns). The prevalence ofM+ in patients (56%) was similar to HV (50%, p=ns). Patients presented a significantlylonger colonic transit time (CTT) and greater production of both H2 and CH4 during LBT(table 1). In the subgroup of M+ the degree of CH4 production is higher in patients comparedto controls. Forty-one (2 men; 21 IBS) finished the treatment and had post-treatmentevaluation. The rate of response to treatment was (56,1 %); similar between M+ (61%) vsM- (50%) p=NS. Responders (n=23) presented similar baseline measures to non-responders(n=18) the degree of CH4 production was similar; final CTT was faster while LBT variablesdid not change significantly (table 2). CONCLUSION: In our population the rate of M+ infunctional constipation is similar to HV. Nevertheless, during LBT, the degree of CH4excretion is significantly higher in constipated patients than HV. We did not observe anassociation between methane status, it's degree of production or change during treatmentand the therapeutic response to fermentable fiber.table 1

Table 2

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Altered Vasoactive Intestinal Peptide (VIP) Expression in Patients WithChronic Abdominal Pain (CAP)Arseima Y. Del Valle-Pinero, Benjamin L. Majors, Angela C. Martino, Ethan M. Anderson,Robert M. Caudle, Wendy A. Henderson

Background: In the United States, up to 20% of individuals suffer from chronic abdominalpain (CAP) of unknown origin. Vasoactive intestinal peptide (VIP) is part of the glucagon-secretin superfamily and it has a wide distribution in the body, such as the heart, lung, anddigestive tract. VIP has many physiological effects including exocrine and endocrine secre-tions, cell differentiation, neuroprotection and the regulation of immune response. VIP hasbeen targeted as a possible drug candidate for several chronic inflammatory diseases suchas asthma and rheumatoid arthritis due to its strong anti-inflammatory effect. VIP is also apotent gut muscle relaxant and alterations in VIP expression has been reported in severalfunctional gastrointestinal disorders including chronic abdominal pain (CAP). We previouslyreported time-dependent changes in VIP protein expression in a rat model of colitis andvisceral hypersensitivity. The aim of this study was to determine VIP gene expression andprotein plasma levels in patients with CAP and healthy controls. Methods: Participants (N =46, 41.30% male, 65.22% Caucasian, ages 14 - 45 years old) were recruited to a prospectivenatural history protocol. The cohort included CAP patients (n = 23) and age, gender, race,and BMI-matched healthy controls (n = 23). Peripheral whole blood and plasma from fastingparticipants was collected. VIP plasma levels were assayed using a VIP peptide-enzymeimmunoassay. RNA was extracted using the PAXgene® Blood RNA tubes and kit. Theexpression of VIP and 83 other genes, was then analyzed in a subgroup of participants (n =24) using a custom quantitative real-time PCR array. Results: VIP gene expression wasupregulated by 2.91-fold in CAP patients (n = 12) when compared to controls (n = 12).Alternatively, VIP protein levels were significantly decreased in CAP patients (n = 23, 0.202± 0.089 ng/ml) when compared to controls (n = 23, 0.274 ± 0.106 ng/ml, p = 0.016).Conclusions: Alterations in vasoactive intestinal peptide gene and protein expression mayplay a pivotal role in CAP. Therefore, a better understanding of the expression, physiologyand pharmacological properties of VIP could lead to the development of therapies thatselectively modulate bowel function and inhibit chronic abdominal pain.

VIP gene expression was upregulated by 2.91-fold in CAP patients compared to controls.

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Post-General Anaesthetic Nausea and Motion Sickness are Associated WithIrritable Bowel Syndrome: A Twin StudyPaul Rastall, Byron T. Theron, Nigel Trudgill, Tim Spector, Juliette Harris

A number of somatic complaints have been found to be associated with irritable bowelsyndrome (IBS) however there is no published evidence of a link with motion sickness orpost-general anaesthetic nausea. Methods All members of the Twins UK registry were invitedto complete a postal questionnaire including the international Rome III IBS questionnaire.

IBS was later classified by both limited and extended criteria and subjects asked aboutmedically diagnosed IBS. The registry includes data collected on motion sickness symptomsand prior experience of nausea and vomiting immediately post-general anaesthetic. Results3074 (94% female, age 56(17-85) years) cases were evaluable for IBS (96.9% with motionsickness data and 75.3% with post-general anaesthetic nausea data). The prevalence of IBSwas 8% for limited Rome III IBS, 22.3% for extended Rome III IBS and 12.6% for medicallydiagnosed IBS. Motion sickness was associated with limited IBS, odds ratio 1.5(95%CI 1.12-2.01) (p=0.006) and medically diagnosed IBS, 1.4(95%CI 1.06-1.74) (p=0.015). Similarlynausea immediately post-general anaesthetic was associated with both (1.4(95%CI 1.03-1.84) (p=0.03) and 1.7(95%CI 1.34-2.17) (p=<0.005) respectively). However with extendedcriteria IBS the association with motion sickness was lost 1.2(95%CI 0.95-1.43) (p=NS) butmaintained for post-general anaesthetic nausea 1.5(95%CI 1.22-1.80) (p=<0.005). Conclu-sions Post-general anaesthetic nausea is clearly associated with IBS. Motion sickness isassociated with limited criteria Rome III and medically diagnosed IBS but not extendedcriteria IBS, a more heterogeneous phenotype with likely greater environmental influences.We suggest that these associations may indicate the common influence of altered centralprocessing of stimuli in the generation of IBS, motion sickness and post-general anaes-thetic nausea.

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Correlation of Circulating Mirnas and Interleukin-10 Levels in Patients Withand Without Chronic Abdominal PainR. Michael Peace, Arseima Y. Del Valle-Pinero, Reyna E. Landis, Angela C. Martino,Nayan S. Patel, Benjamin L. Majors, Wendy A. Henderson

Background: Chronic abdominal pain (CAP) of unknown origin affects 15-20% of peopleworld-wide. Predictive biomarkers are needed to improve assessment of CAP. Our priorwork demonstrated an increased mast cell count in colonic samples from patients with CAP.Interleukin-10 (IL-10) has been shown in mouse models to be produced by mast cells tocounteract inflammatory effects, and in knockout models to be an essential immunoregulatorin the gastrointestinal tract. The aim of the study was to test the expression of circulatingIL-10 and correlating miRNA in patients with and without CAP. Methods: The sample (n =53, age = 27 ± 7.2 years, 47% male and 66% Caucasian), 40% (n=21) with CAP. Fastingblood was collected in EDTA tubes for IL-10 protein levels and measured using Human IL-10 Immunoassay, Quantikine® HS (R & D Systems, Inc., Minneapolis, MN, USA). RNAwas extracted using the PAXGene Blood miRNA extraction kit (Qiagen) from PaxGene tubes,and quantified via spectrophotometry (Nanodrop). In a subgroup of twenty gender, age,race matched samples (10 CAP/10 controls) had PCR array and miRNA performed with thenCounter®HumanmiRNA Sample Preparation Kit (Nanostring) followed by digital detectionand quantification of 735X miRNA withnCounter® Human miRNA Expression Assay Kit(Nanostring). Analyses were done with SPSS v15.0, Partek Genomic Suite for mRNA/miRNAcorrelations and BRB Array Tools with a priori statistical significance set at p≤.05. Results:IL-10 protein levels were significantly higher in CAP (3.18 ± 0.68 pg/mL) compared tocontrols (1.35 ± 0.20 pg/mL). Patients with CAP were 2.4 times more likely to have higherIL-10 levels (Exp(B) 2.43, p=0.003). 340 miRNA were identified via the random varianceestimation procedure (85% with miRNA quantification ≥10 calls) of which 320 passedfiltering criteria. A Randomized block design with a random variance model was used forgroup comparisons. The multiplex targeted profiling revealed eight miRNA that had paramet-ric significance at p ≤.05 and strong correlations with the IL-10 PCR array data includingmiR-220b, miR-548g, miR-362-3p, miR-548i, miR-769-5p, miR-650, miR-133b, miR-934.The most significant of these being miR-220b (r=.73, p=.009). Conclusions: These findingsdemonstrate, not only at the protein but also the genetic level, the justification for noveldiagnostic and treatment methods for this chronic painful disorder.

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Intestinal Motility Patterns and Bacterial Overgrowth in Idiopathic and Post-Infectious Irritable Bowel Syndrome (IBS)Andrew W. Dupont, Zhi-Dong Jiang, Stephen A. Harold, Ned Snyder, Greg Galler,Francisco J. Garcia-Torres, Herbert L. DuPont

Background: The pathophysiology of irritable bowel syndrome (IBS) is incompletely under-stood; however, it has been demonstrated that up to a third of patients develop IBS afteran enteric infection. Disturbances in intestinal motility have been described in some, but notall, patients with IBS. Similarly, the association between small intestinal bacterial overgrowth(SIBO) and IBS has not been clearly defined. It remains to be seen whether intestinaldysmotility is associated with SIBO in patients with post-infectious IBS (PI-IBS) and idiopathicIBS (ID-IBS). Aim: We evaluated alterations in gastrointestinal motility and the presenceSIBO in 25 subjects with PI-IBS (20 females) and 23 subjects with ID-IBS (17 females; p=0.119) seen at a large medical clinic in Houston, Texas. Methods: Gastrointestinal transitwas determined with the use of the SmartPill (SP) wireless pH/pressure recording capsule,which evaluates gastric emptying time (GET), small bowel transit time (SBTT), colonic transittime (CTT), and whole gut transit time (WGTT). After an overnight fast, subjects ingestedthe SP with a nutrient bar (SmartBar, 260 kcal) and were instructed to wear a data receiverfor 5 days. On a separate visit while fasting, subjects ingested 10 g of lactulose and breathsamples were collected every 15 minutes for 180 minutes and analyzed for levels of hydrogenand methane excretion. An abnormal lactulose breath test was defined by an increase of atleast 20 ppm in hydrogen or methane during the first 90 minutes. Results: A total of 18/25 (72%) of the PI-IBS patients and 19/23 (83%) of the ID-IBS patients had prolonged GET(p=0.38) (Table 1). No significant difference was seen between the two groups with respectto abnormal CTT and WGTT. More patients in the PI-IBS group (20%) had prolonged SBTTcompared to ID-IBS (4%); however, the difference did not reach statistical significance. Nosignificant differences were seen in the 3 subtypes of IBS (diarrhea, constipation, mixed)with respect to GTT and SBTT. Among PI-IBS, ID-IBS, and all IBS subjects, constipationpredominance was associated with prolonged CTT and WGTT (Table 2). There was nocorrelation between small bowel transit time and abnormal breath hydrogen or methaneexcretion in the combined 46 patients with IBS. The lowest percentage (45%) of abnormalbreath hydrogen was seen in the IBS patients with rapid SBTT (5/11). Five of six (83%)

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patients with IBS showing delayed small bowel transit had an abnormal breath hydrogentest suggesting the presence of bacterial overgrowth (p=0.29). Conclusion: These resultssuggest delayed gastric emptying is common in patients with IBS, and constipation predomin-ant IBS is associated with prolonged colonic and whole gut transit. A definitive associationbetween prolonged small intestinal transit and bacterial overgrowth cannot be determinedfrom these results.Intestinal Motility Patterns in Patients with Irritable Bowel Syndrome

PI-IBS = post infectious irritable bowel syndrome; ID-IBS = idiopathic irritable bowel syn-drome *Previously validated values for normal transit times were used to define pro-longed transitAssociation of Clinical Type of IBS and Intestinal Transit Times

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Can Symptoms Predict Methanogenesis in Patients With ChronicConstipation?Kalyani Meduri, Robert W. Summers, Ron Schey, Konrad S. Schulze, Jessica Valestin,Satish S. Rao

Background: Methane is produced by approximately 30% of the population, and is associatedwith IBS-C, constipation and slow transit. Methanogenic patients have more severe constipa-tion and slower gut transit than non-methanogenic patients. However, whether methanogenicpatients have specific bowel symptoms that differ from those who do not produce methaneis not known. Aim: To evaluate the symptom profiles and predictive value of symptoms inconstipated patients with methanogenic flora. Methods: Patients with chronic constipation(Rome III) underwent breath testing after being on a restricted diet the day prior to thetest. H2 and CH4 levels were assessed (Quintron breath analyzer). Gastrointestinal symptomswere assessed using a validated questionnaire. The frequency, duration and intensity (score1-3) of ten common symptoms were assessed. Differences in symptom profiles in the twogroups were assessed using ANOVA tests and Pearson Correlation. Results: 102 patientswere assessed. 54 patients (M:F = 5:49, Mean age=48 yrs) were methanogenic and 48patients ( M:F= 8:40, Mean age=50 yrs) were non-methanogenic. There were no significantdifferences in the prevalence of symptoms between the two groups (Table). In the methanog-enic group, the Peak CH4 Value (Mean 57 ppm±5) and AUC of CH4 values during the test(Mean AUC of CH4 8523±1098 ppm.min ) correlated with the presence of Belching andIndigestion at baseline, (p<0.05). The Peak Values of H2 (Mean 10 ppm±2) in the non-methanogenic group correlated with the pre-test occurrence of Nausea (p<0.05). Conclusions:Pre-test GI symptoms or their severity do not predict the presence or absence of methaneon breath testing. Although not perfect, at present, breath testing appears to be the mostpractical method of identifying methanogenesis and symptoms alone are unreliable. Also,certain specific symptoms, such as belching and indigestion may be related to the degreeof methane production.

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