Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease

摘要

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 Saudinationals. 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.