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shealthy controls. Occludin protein levels were decreased by IBS-C FSN or papain infusionin mice colon by 53 and 50% vs healthy FSN or vehicle, respectively, and this effect wasprevented by E64. Occludin degradation was observed in T84 cells incubated with IBS-CFSN or papain, which was prevented by E64. IBS-C FSN and papain degraded recombinantoccludin by 72 and 95% respectively vs healthy controls, an effect partly reversed by E64.Conclusion: This study indicates both In Vivo and In Vitro that elevated cysteine-proteaseactivity found in IBS-C fecal supernatant disrupt tight junction integrity through occludinenzymatic degradation.

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Association of Low Dietary Intake of Fiber and Liquids With Constipation:Evidence From the National Health and Examination Survey (NHANES)Alayne D. Markland, Patricia S. Goode, Olafur S. Palsson, Patricia S. Goode, Kathy L.Burgio, Jan Busby-Whitehead, William E. Whitehead

Background and Aims: Clinical guidelines for managing chronic constipation (CC) includeincreasing fiber, water, and exercise. However, the therapeutic value of these recommenda-tions is disputed. Epidemiological studies support an association of CC (often self-defined)with low fiber and physical activity but not liquid intake. The aims of this study were toassess the association of dietary fiber, total moisture intake, and physical activity to CC.Methods: Data were analyzed for 10,914 adults (≥20 years) who participated in the 2005-2008 cycles of NHANES, a cross-sectional nationally representative survey of the UnitedStates non-institutionalized population. Participants described their usual or most commonstool type using the Bristol Stool Scale (pictures and verbal descriptors provided); CC wasdefined as a response of 1 or 2 (hard or lumpy stool consistency), normal stool consistencyby responses of 3-5. Subjects responding 6 or 7 (loose or watery stools) were excluded fromanalysis. Average dietary fiber and total moisture were calculated from a two-day diet recall.Physical activity was coded 1 for vigorous physical activity at work or leisure; otherwise 0.Additional variables assessed included: age, race, education, poverty income ratio, bodymass index (BMI), self-reported general health status, and number of chronic illnesses.Prevalence estimates and prevalence odds ratios (POR) of CC were analyzed in adjustedmultivariable models using appropriate sampling weights. Results: From the 8674 particip-ants (79%) with stool consistency data, overall CC rates were 11% for women (n=5617)and 4% for men (n=5297), p<.001. Table 1 shows the proportion of men and women withCC in each quartile of fiber and moisture intake. For men, univariate analyses also showeda significant association of CC to age, African American (AA) race, poverty, less education,poor health status, and vigorous physical activity (p<0.05). After multivariable adjustmentin men, low fiber intake (POR 1.2, 95% CI 1.0,1.5), low moisture intake (POR 1.3, 95%CI 1.1,1.7), and physical activity (POR 0.5, 95% CI 0.3,0.9) remained significant predictorsof CC. For women, univariate analyses also showed a significant association of CC to age,AA race, less education, and poor health status (p<0.05). After multivariable adjustment inwomen, higher BMI (POR 1.4, 95% CI 1.2,1.8) and higher education level (POR 1.3, 95%CI 1.1,1.5) were significantly associated with CC; fiber, moisture, and physical activity werenot. Conclusions: For men, clinical recommendations to treat CC with increased fiber,water, and exercise are well supported. For women, increased water and fiber may providesome benefit for CC, but other factors (e.g., BMI) outweigh their contribution [Supportedby R01 DK31369]

930

Small Bowel Culture Confirms the Presence of Small Intestinal BacterialOvergrowth in a Subset of IBS SubjectsManolis Pyleris, Evangelos J. Giamarellos-Bourboulis, Bassileios Koussoulas, CharalambosBarbatzas, Mark Pimentel

There is growing evidence for an association between small intestinal bacterial overgrowth(SIBO) and irritable bowel syndrome (IBS). However, there is little data to prove this conceptvia culture technique. Much of the association has relied on breath testing. In this study,we aimed to define the prevalence of SIBO in IBS based on small bowel culture. MethodsAll consecutive admissions for upper GI tract endoscopy from September 2009 to presentwere eligible for the study. Among this group IBS subjects were identified using Rome IIIcriteria. Exclusion criteria were: a) infection by HIV, HBV or HCV; b) liver cirrhosis; andc) GI tract bleeding. Fluid was aspirated from the second part of the duodenum and it wasquantitatively cultured. Identification of Gram-negative bacteria was performed by API20Esystem. SIBO was defined as the presence of colonic type bacteria at a quantity greater than103 cfu/ml. This cut-off was selected based on 77 healthy controls not taking any drugintake with mean duodenal bacterial counts 5x101 cfu/ml. In a subgroup of subjects, agastric biopsy was obtained to evaluate for the presence of H. pylori. Results A total of 235patients were enrolled; SIBO was present in 47 (20.0%). Eight five patients of the 235subjects (36.2%) were IBS sufferers. In IBS subjects 31 (36.5%) met criteria for SIBOcompared to 10.7% in non-IBS subjects (p< 0.0001). Based on IBS subgroups, the prevalenceof SIBO was 57.1% among those with IBS-predominant diarrhea and 30.2% among thosewithout diarrhea. Body mass index (BMI) of patients with IBS and SIBO was 25.1±5.4compared with 28.3±6.6 among patients with IBS without SIBO (p= 0.041). Isolated speciesfrom the duodenal fluid at quantities greater than 103 cfu/ml were Escherichia coli (9 patients,10.6%), Enterococcus spp (7 patients, 8.2%) and other enterobacteriaceae (12 patients,14.1%) among patients with IBS. Respective isolates among patients without IBS were E.coli(4 patients, 2.7%), Enterococcus spp (7 patients, 4.7%) and other enterobacteriaceae (8patients, 5.3%) (p of comparisons IBS vs non IBS 0.012). Gastric biopsies identifying infectionby Helicobacter pylori (HP) were available in 119 patients. SIBO was not found in any of

S-152AGA Abstracts

the 29 HP+ patients (0%) whereas it was found in 15 of the 90 HP- patients (16.7%, p=0.011). Multiple regression analysis in the total of 235 patients revealed that history of IBSwas the only factor related with the presence of SIBO (OR: 4.93, 95%CI: 2.46-9.88, p<0.0001). The use of gastric pH modifying drugs (OR: 1.77, 95%CI: 0.86-3.62, p= 0.119)was not associated with SIBO. Conclusions: This study is the first to demonstrate that SIBOis implicated in IBS using small bowel culture and an approach that controls for variablessuch as PPI. Interestingly, SIBO appeared to be associated with a lack of HP and lower BMIas well.

931

Genetic Susceptibility to Inflammation is Associated With Colonic Transit andOther Intermediate Phenotypes in Irritable Bowel SyndromeMichael Camilleri, Paula Carlson, Sanna McKinzie, Marco Zucchelli, Mauro D'Amato,Irene A. Busciglio, Duane D. Burton, Alan R. Zinsmeister

Background: We have previously observed associations between Crohn's disease (CD)candidate genes and irritable bowel syndrome (IBS) symptom phenotype. Three other geneshave been associated with post-infectious (PI) IBS. Hypothesis: Candidate genes associatedwith CD or PI-IBS are associatedwith intermediate phenotypes of lower functional gastrointes-tinal disorders (FGID). Aim: To assess association between 30 susceptibility loci for CD,TLR9, IL-6, and CDH1 (previously associated with PI-IBS), and PARM1 (mucin-producing)genes, and quantitative motor and sensory traits in lower FGID. Methods: The primaryendpoint was colonic transit and secondary endpoints: gastrointestinal transit (by scinti-graphy), rectal compliance and sensation (by barostat), and gastric volumes (by SPECT)using validated methods. A 665 person cohort was assembled from prior studies; of these,112 to 172 had quantitative traits measured. TaqMan assay was used for all single nucleotidepolymorphisms (SNPs) associated with the loci of interest. The Wilcoxon rank sum testassessed univariate associations with quantitative traits based on a dominant genetic model(uncorrected nominal p values are reported). Results: Carriers of the TLR9 rs5743836 riskallele had increased odds for IBS-D (vs control, p=0.02). Among the CD risk loci, C11orf30rs7927894 (p=0.007), PRDM1 rs7746082 (p=0.011), ORMDL3 rs2872507 (p=0.014),together with TLR9 rs5743836 (p=0.010) were univariately associated with colonic transitat 24 or 48h; PRDM1 rs7746082 (p=0.04), ZNF365 rs10995271 (p=0.0026), JAK2rs10758669 (p=0.0221) and PTPN2 rs2542151 (p=0.027) with rectal compliance; CDH1rs16260 (p=0.034) with rectal pain; and C13orf31 rs3764147 (p=0.0027) with rectal urgencysensation. Examination of 4 specific gene pairs at 3 different loci [PRDM1 rs7746082 withTLR9 rs5743836 or with ORMDL3 rs2872507, and C11orf30 rs7927894 with ORMDL3rs2872507] revealed potential associations between genes that influence neural, barrier ormast cell function and colonic transit. Conclusion: Genetic variations in local barrier andimmune function and, possibly, enteric neural development are univariately associated withaltered colonic transit in IBS. These data support the hypothesis of local immune activationas a contributing factor to the development of lower FGID.

932

Serum Anti-Glycan Antibody Biomarkers for Inflammatory Bowel DiseaseDiagnosis and Progression: A Meta-AnalysisAmit Kaul, Susan Hutfless, Michael R. Marohn, Xuhang Li

BACKGROUND: Anti-glycan antibody serologic markers may be useful in the diagnosis andprognosis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerativecolitis (UC). The diagnostic value and predictive ability of the anti-glycan antibodies havenot been systematically evaluated across studies. We aimed to perform a meta-analysis ofthe diagnostic and prognostic value of the anti-glycan antibodies. METHODS: Pubmed wassearched through October 2010. Included studies compared the sensitivity and specificityof at least two anti-glycan antibody markers (ASCA, AMCA, ALCA, ACCA, Anti-L and Anti-C) with at least one of the following outcomes: differentiating IBD from non-IBD; CD fromUC; need for CD surgery; or penetrating CD. Pooled sensitivity and specificity were calculatedusing random-effects models and summarized with the diagnostic odds ratio (DOR) whichcompares the odds of being correctly classified (true positive or negative) to being incorrectlyclassified (false positive or negative). The DOR was calculated for individual markers andpositivity on ≥2 markers compared to positivity for ≤1 marker. Identifying the increase inpredictive ability using specific combinations of markers was not possible, because studiesreported on the number of positive markers only and did not specify which markers testedpositive. RESULTS: Twelve studies met the inclusion criteria. Individually, ASCA had thehighest DOR for differentiating IBD from non-IBD (DOR 32.3; 95% confidence interval [CI]4.7-221.8; 3 studies) and CD from UC (DOR 11.4; CI 9.3-13.8; 7 studies). The DORs fordifferentiating CD from UC for the other markers were Anti-L 5.3, ALCA 3.5, Anti-C 3.4,AMCA 2.5, and ACCA 1.9. When positivity for ≥2 markers was used to distinguish CDfrom UC the DOR was 14.3 (95% CI 5.3-38.6; 2 studies). The DORs for ASCA alone and≥2 positive markers were similar for CD-related surgery (ASCA DOR 2.0 [CI 1.6-2.4; 4studies]; ≥2 DOR 2.7 [CI 2.2-3.2; 4 studies). The DOR for ≥2 markers with penetratingdisease was 2.2 (CI 1.7-2.9; 2 studies). Individual anti-glycan markers were not evaluatedfor penetrating disease in the included studies. CONCLUSIONS: ASCA appears to be themost predictive of the anti-glycan markers for differentiating IBD from non-IBD and CDfrom UC. This analysis indicates that a combination of more than two markers increasespredictive ability for CD related penetrating disease, ileal involvement, and need for surgery.However, more studies are needed to identify which combination of the anti-glycan markershas the greatest prognostic value for CD and UC.