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Role of gut microbiota in the pathogenesis of celiac disease
A42
Abstracts / Digestive and Liver Disease 40 (2008) A41–A118
wall thickness (>3 mm) and strictures as reduced luminal diameter (<1 cm). Aim. To evaluate the clinical usefulness of the two X-ray free, non-invasive procedures SICUS and CE in assessing mural and endoluminal pathology in pediatric patients with known or suspected small bowel disease. Subjects and methods. Sixteen patients (4 F, median age 16 years; range 9–20 years) were consecutively enrolled: 2 pts with suspected CD; 13 pts with a diagnosis of CD, of which 2 pts had previous ileo-colonic resection for strictures, 1 pt with intestinal polyps. Before CE, SICUS (Tosbee equipment, Toshiba Japan, with 5 MHz linear and 3.5 MHz convex array transducers) was performed by a sonologist, unaware of other radiological and endoscopic findings after the ingestion of 125–500 ml of macrogol solution. All pts had swallowed CE (Given M2A capsule, Given Imaging); the day before the examination they received an intestinal preparation with 3 L of polyethylene–glycol solution. Results. SICUS was performed in 15 pts, one patient refused. Five pts had one or more small bowel strictures detected at SICUS and CE could not be performed. In the 11 patients submitted to both procedures, SICUS and CE detected lesions at the level of distal and terminal ileum in 10 pts with diagnosis of CD, confirmed at standard endoscopy. In the 2 pts with ileocolonic resection both techniques were able to individuate CD recurrence in ileocolonic anastomosis. In 3 pts CE also showed jejunum and proximal ileum erosions not detectable at SICUS. In the remaining patient both techniques detected jejunal and proximal ileal lesions compatible with the diagnosis of intestinal polyps. Conclusions. These findings suggest: (1) the opportunity to perform SICUS before CE to exclude the presence of small bowel strictures; (2) the usefulness of non-invasive SICUS and CE techniques in the more accurate assessment of wall and luminal small bowel lesions, respectively; (3) the possibility to avoid radiation exposure. In conclusion CE and SICUS may be used as non-invasive complementary techniques for the assessment of small bowel diseases in pediatric patients, avoiding X-ray exposure.
prolamins and appropriate HLA-DQ haplotype are necessary but not sufficient for contracting CD. Although modification of gut microbiota seems to be involved in the pathogenesis of other chronic inflammatory bowel diseases (IBD), its possible role in CD has never been investigated. Aims. To identify by a molecular approach the microbiota colonizing the upper small bowel of children with CD at diagnosis and after 8 months of gluten free diet (GFD). Methods. Mucosal-associated bacteria from duodenal biopsies of 10 celiac children aged 5–15 years, (at diagnosis and after 8 months of GFD), and of 8 healthy controls were investigated. Total DNA was extracted, and 16S ribosomal DNA was amplified by PCR. Amplification products were separated by temporal temperature gradient gel electrophoresis (TTGE) a powerful technique for comparing the biodiversity of the dominant microbiota in different biological samples. The profiles obtained were analyzed using GelQuest software (Sequentix) providing a dendogram based on the agglomeration method of UPGMA. Result. The dendogram obtained reveals two clusters sharing high degrees of similarity. The first cluster includes all active disease patients, the second one those in GFD. TTGE profiles of controls clustered with celiac children in GFD. Interestingly dominant microbiota in active disease differed very much from remission and controls. Conclusion. This is the first paediatric report investigating the duodenal mucosa-associated microbiota in celiac children at diagnosis and after GFD. The main result of the present study, although limited by the sample size, highlighted TTGE profiles clusters with clinical status of CD. These preliminary data showed that dominant duodenal microbiota in active disease seems to differ very much from that in remission. These findings suggest a pathogenetic role in CD. Further studies will sequence different DNA fragments, specific for each profile, to identify dominant microbial species characterizing intestinal microbiota in active and in remission disease.
doi:10.1016/j.dld.2008.07.175
doi:10.1016/j.dld.2008.07.176
CO3 ROLE OF GUT MICROBIOTA IN THE PATHOGENESIS OF CELIAC DISEASE
CO4 LONG-TERM STUDY OF PATIENTS WITH POTENTIAL CELIAC DISEASE
M. Barbato a , V. Iebba b , M.P. Conte b , S. Schippa b , O. Borrelli a , G. Maiella a , C. Longhi b , V. Totino b , F. Viola a , S. Cucchiara a
M.F. Brambillasca, B. Parma, G. Tronconi, P. Corsin, G. Barera
a
Pediatric Gastroenterology and Live Unit of the University of Rome “La Sapienza”, Italy b Microbiology Laboratory of the Public Health Department of the University of Rome “La Sapienza”, Italy Background. Celiac disease (CD) is an immune-mediated enteropathy, characterized by small bowel chronic inflammation. Its pathogenesis is multifactorial: exposure to toxic
Department of Pediatrics, Scientific Institute H. San Raffaele, Vita-Salute University, Milan, Italy Potential celiac disease (CD) is characterized by normal histologic features associated with gluten dependent autoantibodies regardless of symptoms. Most of these patients have DQ2/DQ8 haplotype. The outcome is variable and unpredictable; sometimes histologic picture remains normal for long time, some others it progresses to overt villous atrophy.
Abstracts / Digestive and Liver Disease 40 (2008) A41–A118
wall thickness (>3 mm) and strictures as reduced luminal diameter (<1 cm). Aim. To evaluate the clinical usefulness of the two X-ray free, non-invasive procedures SICUS and CE in assessing mural and endoluminal pathology in pediatric patients with known or suspected small bowel disease. Subjects and methods. Sixteen patients (4 F, median age 16 years; range 9–20 years) were consecutively enrolled: 2 pts with suspected CD; 13 pts with a diagnosis of CD, of which 2 pts had previous ileo-colonic resection for strictures, 1 pt with intestinal polyps. Before CE, SICUS (Tosbee equipment, Toshiba Japan, with 5 MHz linear and 3.5 MHz convex array transducers) was performed by a sonologist, unaware of other radiological and endoscopic findings after the ingestion of 125–500 ml of macrogol solution. All pts had swallowed CE (Given M2A capsule, Given Imaging); the day before the examination they received an intestinal preparation with 3 L of polyethylene–glycol solution. Results. SICUS was performed in 15 pts, one patient refused. Five pts had one or more small bowel strictures detected at SICUS and CE could not be performed. In the 11 patients submitted to both procedures, SICUS and CE detected lesions at the level of distal and terminal ileum in 10 pts with diagnosis of CD, confirmed at standard endoscopy. In the 2 pts with ileocolonic resection both techniques were able to individuate CD recurrence in ileocolonic anastomosis. In 3 pts CE also showed jejunum and proximal ileum erosions not detectable at SICUS. In the remaining patient both techniques detected jejunal and proximal ileal lesions compatible with the diagnosis of intestinal polyps. Conclusions. These findings suggest: (1) the opportunity to perform SICUS before CE to exclude the presence of small bowel strictures; (2) the usefulness of non-invasive SICUS and CE techniques in the more accurate assessment of wall and luminal small bowel lesions, respectively; (3) the possibility to avoid radiation exposure. In conclusion CE and SICUS may be used as non-invasive complementary techniques for the assessment of small bowel diseases in pediatric patients, avoiding X-ray exposure.
prolamins and appropriate HLA-DQ haplotype are necessary but not sufficient for contracting CD. Although modification of gut microbiota seems to be involved in the pathogenesis of other chronic inflammatory bowel diseases (IBD), its possible role in CD has never been investigated. Aims. To identify by a molecular approach the microbiota colonizing the upper small bowel of children with CD at diagnosis and after 8 months of gluten free diet (GFD). Methods. Mucosal-associated bacteria from duodenal biopsies of 10 celiac children aged 5–15 years, (at diagnosis and after 8 months of GFD), and of 8 healthy controls were investigated. Total DNA was extracted, and 16S ribosomal DNA was amplified by PCR. Amplification products were separated by temporal temperature gradient gel electrophoresis (TTGE) a powerful technique for comparing the biodiversity of the dominant microbiota in different biological samples. The profiles obtained were analyzed using GelQuest software (Sequentix) providing a dendogram based on the agglomeration method of UPGMA. Result. The dendogram obtained reveals two clusters sharing high degrees of similarity. The first cluster includes all active disease patients, the second one those in GFD. TTGE profiles of controls clustered with celiac children in GFD. Interestingly dominant microbiota in active disease differed very much from remission and controls. Conclusion. This is the first paediatric report investigating the duodenal mucosa-associated microbiota in celiac children at diagnosis and after GFD. The main result of the present study, although limited by the sample size, highlighted TTGE profiles clusters with clinical status of CD. These preliminary data showed that dominant duodenal microbiota in active disease seems to differ very much from that in remission. These findings suggest a pathogenetic role in CD. Further studies will sequence different DNA fragments, specific for each profile, to identify dominant microbial species characterizing intestinal microbiota in active and in remission disease.
doi:10.1016/j.dld.2008.07.175
doi:10.1016/j.dld.2008.07.176
CO3 ROLE OF GUT MICROBIOTA IN THE PATHOGENESIS OF CELIAC DISEASE
CO4 LONG-TERM STUDY OF PATIENTS WITH POTENTIAL CELIAC DISEASE
M. Barbato a , V. Iebba b , M.P. Conte b , S. Schippa b , O. Borrelli a , G. Maiella a , C. Longhi b , V. Totino b , F. Viola a , S. Cucchiara a
M.F. Brambillasca, B. Parma, G. Tronconi, P. Corsin, G. Barera
a
Pediatric Gastroenterology and Live Unit of the University of Rome “La Sapienza”, Italy b Microbiology Laboratory of the Public Health Department of the University of Rome “La Sapienza”, Italy Background. Celiac disease (CD) is an immune-mediated enteropathy, characterized by small bowel chronic inflammation. Its pathogenesis is multifactorial: exposure to toxic
Department of Pediatrics, Scientific Institute H. San Raffaele, Vita-Salute University, Milan, Italy Potential celiac disease (CD) is characterized by normal histologic features associated with gluten dependent autoantibodies regardless of symptoms. Most of these patients have DQ2/DQ8 haplotype. The outcome is variable and unpredictable; sometimes histologic picture remains normal for long time, some others it progresses to overt villous atrophy.