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Chapel Hill, NC, United States

Jensen E.T.,Center for Esophageal Diseases and Swallowing | Martin C.F.,Center for Gastrointestinal Biology and Disease | Kappelman M.D.,University of North Carolina at Chapel Hill | Dellon E.S.,Center for Esophageal Diseases and Swallowing
Journal of Pediatric Gastroenterology and Nutrition | Year: 2016

Objectives: Eosinophilic esophagitis (EoE) is becoming increasingly more common, but the prevalence of other eosinophilic gastrointestinal disorders (EGIDs) is unknown. Our objective was to estimate the prevalence of eosinophilic gastritis, gastroenteritis, and colitis in the United States. Methods: We used the IMS Health LifeLink PharMetrics Plus Claims Database, data representative of a US national commercially insured population containing medical and pharmaceutical claims for >75 million individuals. We restricted our sample to patients ages 0 to 64 with continuous enrollment between July 1, 2009, and June 30, 2011. We identified patients with eosinophilic gastritis, gastroenteritis, and colitis as defined by ≥1 instance of the International Classification of Diseases, Ninth Revision codes 535.70, 558.41, and 558.42, respectively. Wecalculated the prevalence of the codes in the database and then standardized the estimates to the US population by age and sex. © 2015 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Source


Shen X.J.,Center for Gastrointestinal Biology and Disease
Gut microbes | Year: 2010

The human large bowel is colonized by complex and diverse bacterial communities. However, the relationship between commensal bowel bacteria and adenomas (colorectal cancer precursors) is unclear. This study aimed to characterize adherent bacteria in normal colon and evaluate differences in community composition associated with colorectal adenomas. We evaluated adherent bacteria in normal colonic mucosa of 21 adenoma and 23 non-adenoma subjects enrolled in a cross sectional study. Terminal restriction fragment length polymorphism, clone sequencing and fluorescent in-situ hybridization analysis of the 16S rRNA genes were used to characterize adherent bacteria. A total of 335 clones were sequenced and processed for phylogenetic and taxonomic analysis. Differences in bacterial composition between cases and controls were evaluated by UniFrac and analysis of similarity matrix. Overall, Firmicutes (62%), Bacteroidetes (26%) and Proteobacteria (11%) were the most dominant phyla. The bacterial composition differed significantly between cases and controls (UniFrac p < 0.001). We observed significantly higher abundance of Proteobacteria (p < 0.05) and lower abundance of Bacteroidetes (p < 0.05) in cases compared to controls. At the genus level, case subjects showed increased abundance of Dorea spp. (p < 0.005), Faecalibacterium spp. (p < 0.05) and lower proportions of Bacteroides spp. (p < 0.03) and Coprococcus spp. (p < 0.05) than controls. Cases had higher bacterial diversity and richness than controls. These findings reveal that alterations in bacterial community composition associated with adenomas may contribute to the etiology of colorectal cancer. Extension of these findings could lead to strategies to manipulate the microbiota to prevent colorectal adenomas and cancer as well as to identify individuals at high risk. Source


Carroll I.M.,Center for Gastrointestinal Biology and Disease | Ringel-Kulka T.,University of North Carolina at Chapel Hill | Keku T.O.,Center for Gastrointestinal Biology and Disease | Chang Y.-H.,Korea Research Institute of Bioscience and Biotechnology | And 3 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2011

Alterations in the intestinal microbiota have been suggested as an etiological factor in the pathogenesis of irritable bowel syndrome (IBS). This study used a molecular fingerprinting technique to compare the composition and biodiversity of the microbiota within fecal and mucosal niches between patients with diarrhea-predominant IBS (D-IBS) and healthy controls. Terminal-restriction fragment (T-RF) length polymorphism (T-RFLP) fingerprinting of the bacterial 16S rRNA gene was used to perform microbial community composition analyses on fecal and mucosal samples from patients with D-IBS (n = 16) and healthy controls (n = 21). Molecular fingerprinting of the microbiota from fecal and colonic mucosal samples revealed differences in the contribution of T-RFs to the microbiota between D-IBS patients and healthy controls. Further analysis revealed a significantly lower (1.2-fold) biodiversity of microbes within fecal samples from D-IBS patients than healthy controls (P = 0.008). No difference in biodiversity in mucosal samples was detected between D-IBS patients and healthy controls. Multivariate analysis of T-RFLP profiles demonstrated distinct microbial communities between luminal and mucosal niches in all samples. Our findings of compositional differences in the luminal- and mucosal-associated microbiota between D-IBS patients and healthy controls and diminished microbial biodiversity in D-IBS fecal samples further support the hypothesis that alterations in the intestinal microbiota may have an etiological role in the pathogenesis of D-IBS and suggest that luminal and mucosal niches need to be investigated. © 2011 the American Physiological Society. Source


Nighot P.,North Carolina State University | Nighot P.,University of New Mexico | Young K.,North Carolina State University | Nighot M.,North Carolina State University | And 8 more authors.
Inflammatory Bowel Diseases | Year: 2013

Background: Previously, it was shown that the chloride channel ClC-2 modulates intestinal tight junction (TJ) barrier function. The aim of the present study was to investigate the role of ClC-2 in epithelial barrier function and recovery in the event of epithelial injury. Methods: The role of ClC-2 was investigated in TJ barrier function in dextran sodium sulfate (DSS)-induced colitis in ClC-2 knockout mice and ClC-2 knockdown intestinal Caco-2 cells. Barrier function was measured electrophysiologically and by transepithelial mannitol fluxes. Selected TJ and associated proteins were Western blotted, cytokines were measured using quantitative PCR, and human colonic biopsies were examined with immunohistochemistry. Results: ClC-2-/- mice had a higher disease activity index, higher histological scores, and increased paracellular permeability compared with wild-type mice when treated with DSS. DSS-treated ClC-2-/- mice had increased claudin-2 expression, greater loss of occludin in the membrane, increased association of occludin with caveolin-1, and significantly increased tumor necrosis factor-a and interleukin-1β messenger RNA. ClC-2 knockdown in human intestinal Caco-2 cells resulted in a greater loss of epithelial resistance in the event of epithelial injury. The restoration of colonic barrier function after DSS colitis was delayed in ClC-2-/- mice. In human colonic biopsies, the protein and messenger RNA expression of ClC-2 was found to be reduced in patients with ulcerative colitis. Conclusions: ClC-2 plays a critical role in experimental colitis in that its absence increases disease activity, reduces barrier function and recovery, and perturbs TJs. Furthermore, ClC-2 expression is markedly reduced in the colon of human patients with ulcerative colitis. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc. Source


Long M.D.,University of North Carolina at Chapel Hill | Long M.D.,Center for Gastrointestinal Biology and Disease | Kappelman M.D.,Center for Gastrointestinal Biology and Disease | Kappelman M.D.,University of North Carolina at Chapel Hill | And 7 more authors.
Inflammatory Bowel Diseases | Year: 2012

Background: The widespread use of the Internet allows for unique research opportunities. We aimed to develop and follow an Internet-based cohort (e-cohort) of patients with self-reported inflammatory bowel diseases (IBD) over time. Methods: We established an e-cohort of adults with IBD (CCFA Partners) by recruiting through Crohn's and Colitis Foundation of America (CCFA) email rosters, CCFA Website promotion, social media, and other publicity mechanisms. The baseline survey included modules on disease course and activity, diet and exercise, and patient-reported outcomes (PROs). Baseline characteristics of the cohort are summarized using descriptive statistics. Results: A total of 7819 adults with IBD joined CCFA Partners through August, 2011. The median age was 42 years (interquartile range [IQR] 30-54), 5074 (72.3%) were female. A total of 4933 (63.1%) had Crohn's disease (CD), 2675 (34.2%) had ulcerative colitis (UC), and 211 (2.7%) had IBD unspecified. For CD, the mean short CD Activity Index (CDAI) was 151.9 (standard deviation [SD] 106.4), with 2274 (59.4%) in remission. For UC, the mean simple clinical colitis activity index (SCCAI) was 3.6 (SD 2.8), with 937 (42.9%) in remission. The mean short IBD questionnaire (SIBDQ) score was 48.7 (SD 11.8). SIBDQ was inversely correlated with disease activity (P < 0.01). The mean Morisky medication adherence score (MMAS) was 5.7 (SD 2.0). MMAS scores were inversely correlated with disease activity (P < 0.01). Conclusions: CCFA Partners is a novel e-cohort. Enrollment is ongoing, with surveys twice yearly. CCFA Partners represents a unique resource to study PROs and changes in disease management over time. (Inflamm Bowel Dis 2012;) Copyright © 2012 Crohn's & Colitis Foundation of America, Inc. Source

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