AIM To investigate the accuracy of fungal dysbiosis inmucosa and stool for predicting the diagnosis of Crohn's disease(CD). METHODS Children were prospectively enrolled in two medical centers: one university hospi...AIM To investigate the accuracy of fungal dysbiosis inmucosa and stool for predicting the diagnosis of Crohn's disease(CD). METHODS Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer's protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve(AUC) was calculated. RESULTS All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9(range: 6.7-17.8) years for CD children and 13.9(3.25-18.6) years for controls, and 10/15(67%) of the CD and 13/20(65%) of the control subjects were boys. CD locations at diagnosis were ileal(L1) in 4 and colonic(L3) in 11 children, while CD behavior was non-stricturing and non-penetrating(B1) in 12 and stricturing(B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools(AUC = 0.85 ± 0.057) than in mucosa(AUC = 0.71 ± 0.067)(P < 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for Saccharomyces cerevisiae and S. bayanus, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa. CONCLUSION We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD.展开更多
BACKGROUND Incidence and severity variations of inflammatory bowel disease(IBD)have been reported from Western populations between continents and regions of the same countries.However,no data were available from other...BACKGROUND Incidence and severity variations of inflammatory bowel disease(IBD)have been reported from Western populations between continents and regions of the same countries.However,no data were available from other countries.AIM To investigate the regional differences in the IBD profiles of pediatric patients from the Kingdom of Saudi Arabia.METHODS Data from a national multicenter IBD study were used.The incidence,time trend,and clinical presentation of Crohn’s disease(CD)and ulcerative colitis(UC)in the Central region(CR),Western region(WR),and Eastern region(ER)were analyzed and compared.Statistical analysis included Poisson regression analysis for incidence variation and Chi-square test for demographic and clinical parameters.A P<0.05 was considered significant.RESULTS The prevalence of positive family history was lower in children with CD from the ER than the CR or the WR.Consanguinity rate was higher in children with CD and UC from the CR and the ER,respectively.The incidences and time trends of CD and UC were not significantly different between regions.In the ER,a significantly higher percentage of children with CD presented with abdominal pain(P<0.001),blood in stools(P=0.048),stricturing or penetrating disease(P=0.029),higher erythrocyte sedimentation rate(P<0.001),higher C-reactive protein(P<0.001),higher anemia(P=0.017),and lower albumin level(P=0.014).For children with UC from the ER,a significantly higher percentage presented with anemia(P=0.006)and a lower percentage with pancolitis(P<0.001).CONCLUSION The most important finding is the identification of significantly more severe presentation of CD in the ER of the Kingdom of Saudi Arabia.Prospective studies are needed to explain such variations.展开更多
基金supported by a grant from the Simons Foundation [No.409704] to Kirill Korolev) the startup fund from Boston University to Kirill Korolev+2 种基金Simulations were carried out on Shared Computing Cluster at Boston University Rajita Menon was partially supported by a Hariri Graduate Fellowship from Boston UniversityHarland Winter, MD received support from Martin Schlaff and the Diane and Dorothy Brooks Foundation
文摘AIM To investigate the accuracy of fungal dysbiosis inmucosa and stool for predicting the diagnosis of Crohn's disease(CD). METHODS Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer's protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve(AUC) was calculated. RESULTS All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9(range: 6.7-17.8) years for CD children and 13.9(3.25-18.6) years for controls, and 10/15(67%) of the CD and 13/20(65%) of the control subjects were boys. CD locations at diagnosis were ileal(L1) in 4 and colonic(L3) in 11 children, while CD behavior was non-stricturing and non-penetrating(B1) in 12 and stricturing(B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools(AUC = 0.85 ± 0.057) than in mucosa(AUC = 0.71 ± 0.067)(P < 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for Saccharomyces cerevisiae and S. bayanus, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa. CONCLUSION We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD.
基金Supported by the Deanship for Scientific Research,King Saud University,Riyadh,Kingdom of Saudi Arabia,No.RGP-1436-007
文摘BACKGROUND Incidence and severity variations of inflammatory bowel disease(IBD)have been reported from Western populations between continents and regions of the same countries.However,no data were available from other countries.AIM To investigate the regional differences in the IBD profiles of pediatric patients from the Kingdom of Saudi Arabia.METHODS Data from a national multicenter IBD study were used.The incidence,time trend,and clinical presentation of Crohn’s disease(CD)and ulcerative colitis(UC)in the Central region(CR),Western region(WR),and Eastern region(ER)were analyzed and compared.Statistical analysis included Poisson regression analysis for incidence variation and Chi-square test for demographic and clinical parameters.A P<0.05 was considered significant.RESULTS The prevalence of positive family history was lower in children with CD from the ER than the CR or the WR.Consanguinity rate was higher in children with CD and UC from the CR and the ER,respectively.The incidences and time trends of CD and UC were not significantly different between regions.In the ER,a significantly higher percentage of children with CD presented with abdominal pain(P<0.001),blood in stools(P=0.048),stricturing or penetrating disease(P=0.029),higher erythrocyte sedimentation rate(P<0.001),higher C-reactive protein(P<0.001),higher anemia(P=0.017),and lower albumin level(P=0.014).For children with UC from the ER,a significantly higher percentage presented with anemia(P=0.006)and a lower percentage with pancolitis(P<0.001).CONCLUSION The most important finding is the identification of significantly more severe presentation of CD in the ER of the Kingdom of Saudi Arabia.Prospective studies are needed to explain such variations.