Tu1446 Intestinal Motility Patterns and Bacterial Overgrowth in Idiopathic and Post-Infectious Irritable Bowel Syndrome (IBS)

patients with IBS showing delayed small bowel transit had an abnormal breath hydrogen test suggesting the presence of bacterial overgrowth (p=0.29). Conclusion: These results suggest delayed gastric emptying is common in patients with IBS, and constipation predominant IBS is associated with prolonged colonic and whole gut transit. A definitive association between prolonged small intestinal transit and bacterial overgrowth cannot be determined from these results. Intestinal Motility Patterns in Patients with Irritable Bowel Syndrome

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

Tu1445 Correlation of Circulating Mirnas and Interleukin-10 Levels in Patients With and Without Chronic Abdominal Pain R. 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 people world-wide. Predictive biomarkers are needed to improve assessment of CAP. Our prior work 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 to counteract inflammatory effects, and in knockout models to be an essential immunoregulator in the gastrointestinal tract. The aim of the study was to test the expression of circulating IL-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. Fasting blood was collected in EDTA tubes for IL-10 protein levels and measured using Human IL10 Immunoassay, Quantikine® HS (R & D Systems, Inc., Minneapolis, MN, USA). RNA was 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 the nCounter® Human miRNA Sample Preparation Kit (Nanostring) followed by digital detection and quantification of 735X miRNA withnCounter® Human miRNA Expression Assay Kit (Nanostring). Analyses were done with SPSS v15.0, Partek Genomic Suite for mRNA/miRNA correlations 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 to controls (1.35 ± 0.20 pg/mL). Patients with CAP were 2.4 times more likely to have higher IL-10 levels (Exp(B) 2.43, p=0.003). 340 miRNA were identified via the random variance estimation procedure (85% with miRNA quantification ≥10 calls) of which 320 passed filtering criteria. A Randomized block design with a random variance model was used for group comparisons. The multiplex targeted profiling revealed eight miRNA that had parametric significance at p ≤.05 and strong correlations with the IL-10 PCR array data including miR-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 findings demonstrate, not only at the protein but also the genetic level, the justification for novel diagnostic and treatment methods for this chronic painful disorder.

Tu1447 Can Symptoms Predict Methanogenesis in Patients With Chronic Constipation? 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 associated with IBS-C, constipation and slow transit. Methanogenic patients have more severe constipation and slower gut transit than non-methanogenic patients. However, whether methanogenic patients have specific bowel symptoms that differ from those who do not produce methane is not known. Aim: To evaluate the symptom profiles and predictive value of symptoms in constipated patients with methanogenic flora. Methods: Patients with chronic constipation (Rome III) underwent breath testing after being on a restricted diet the day prior to the test. H2 and CH4 levels were assessed (Quintron breath analyzer). Gastrointestinal symptoms were assessed using a validated questionnaire. The frequency, duration and intensity (score 1-3) of ten common symptoms were assessed. Differences in symptom profiles in the two groups were assessed using ANOVA tests and Pearson Correlation. Results: 102 patients were assessed. 54 patients (M:F = 5:49, Mean age=48 yrs) were methanogenic and 48 patients ( M:F= 8:40, Mean age=50 yrs) were non-methanogenic. There were no significant differences in the prevalence of symptoms between the two groups (Table). In the methanogenic 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 and Indigestion at baseline, (p<0.05). The Peak Values of H2 (Mean 10 ppm±2) in the nonmethanogenic 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 methane on breath testing. Although not perfect, at present, breath testing appears to be the most practical method of identifying methanogenesis and symptoms alone are unreliable. Also, certain specific symptoms, such as belching and indigestion may be related to the degree of methane production.

Tu1446 Intestinal Motility Patterns and Bacterial Overgrowth in Idiopathic and PostInfectious 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 understood; however, it has been demonstrated that up to a third of patients develop IBS after an enteric infection. Disturbances in intestinal motility have been described in some, but not all, 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 intestinal dysmotility is associated with SIBO in patients with post-infectious IBS (PI-IBS) and idiopathic IBS (ID-IBS). Aim: We evaluated alterations in gastrointestinal motility and the presence SIBO 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 transit was 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 transit time (CTT), and whole gut transit time (WGTT). After an overnight fast, subjects ingested the SP with a nutrient bar (SmartBar, 260 kcal) and were instructed to wear a data receiver for 5 days. On a separate visit while fasting, subjects ingested 10 g of lactulose and breath samples were collected every 15 minutes for 180 minutes and analyzed for levels of hydrogen and methane excretion. An abnormal lactulose breath test was defined by an increase of at least 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 respect to abnormal CTT and WGTT. More patients in the PI-IBS group (20%) had prolonged SBTT compared to ID-IBS (4%); however, the difference did not reach statistical significance. No significant 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, constipation predominance was associated with prolonged CTT and WGTT (Table 2). There was no correlation between small bowel transit time and abnormal breath hydrogen or methane excretion in the combined 46 patients with IBS. The lowest percentage (45%) of abnormal breath hydrogen was seen in the IBS patients with rapid SBTT (5/11). Five of six (83%)

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AGA Abstracts

AGA Abstracts

IBS was later classified by both limited and extended criteria and subjects asked about medically diagnosed IBS. The registry includes data collected on motion sickness symptoms and prior experience of nausea and vomiting immediately post-general anaesthetic. Results 3074 (94% female, age 56(17-85) years) cases were evaluable for IBS (96.9% with motion sickness data and 75.3% with post-general anaesthetic nausea data). The prevalence of IBS was 8% for limited Rome III IBS, 22.3% for extended Rome III IBS and 12.6% for medically diagnosed IBS. Motion sickness was associated with limited IBS, odds ratio 1.5(95%CI 1.122.01) (p=0.006) and medically diagnosed IBS, 1.4(95%CI 1.06-1.74) (p=0.015). Similarly nausea immediately post-general anaesthetic was associated with both (1.4(95%CI 1.031.84) (p=0.03) and 1.7(95%CI 1.34-2.17) (p=<0.005) respectively). However with extended criteria IBS the association with motion sickness was lost 1.2(95%CI 0.95-1.43) (p=NS) but maintained for post-general anaesthetic nausea 1.5(95%CI 1.22-1.80) (p=<0.005). Conclusions Post-general anaesthetic nausea is clearly associated with IBS. Motion sickness is associated with limited criteria Rome III and medically diagnosed IBS but not extended criteria IBS, a more heterogeneous phenotype with likely greater environmental influences. We suggest that these associations may indicate the common influence of altered central processing of stimuli in the generation of IBS, motion sickness and post-general anaesthetic nausea.