Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease

AIM: To investigate the accuracy of fungal dysbiosis in mucosa 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. Key Words: Fungiome, Mycobiome, Crohn’s disease, Inflammation, Saudi children Core tip: We found high accuracy of fungal dysbiosis in predicting diagnosis of Crohn’s disease (CD), a finding similar to bacterial dysbiosis. However, the higher area under the curve for the fungal dysbiosis classifier in stool (0.85 ± 0.057) than in mucosa (0.71 ± 0.067) (P < 0.001), contrasts with bacterial studies, suggesting higher accuracy of stool samples. Although the clinical application of this finding is limited at present by the high cost of fungal analysis, such information is important from a scientific viewpoint, to increase the understanding of the role of fungal flora in CD and to stimulate further studies.The authors extend their appreciations to the Deanship of Scientific Research at King Saud University in Riyadh, Kingdom of Saudi Arabia for funding this work through Research Group No [RGP-1436-007]. This work was also supported by a grant from the Simons Foundation [No. 409704] to Kirill Korolev) and by the startup fund from Boston University to Kirill Korolev. Simulations were carried out on Shared Computing Cluster at Boston University. Rajita Menon was partially supported by a Hariri Graduate Fellowship from Boston University. Harland Winter, MD received support from Martin Schlaff and the Diane and Dorothy Brooks Foundation. (RGP-1436-007 - King Saud University in Riyadh, Kingdom of Saudi Arabia; 409704 - Simons Foundation; Boston University; Hariri Graduate Fellowship from Boston University; Diane and Dorothy Brooks Foundation)Published versio

The Epidemiology and Outcome of Biliary Atresia: Saudi Arabian National Study (2000–2018)

BackgroundThe epidemiology and outcomes of biliary atresia (BA) have been well-documented in national cohorts from two main ethnicities, namely, the Asian Orientals and Caucasians, with incidence ranging from 1 in 5,000 to 1 in 9,000 live births in East Asia and 1 in 15,000 to 19,000 live births in Europe and North America.ObjectiveWe report the first nationwide BA study outside North America, Europe, and East Asia to describe the epidemiology and outcomes of BA in Saudi Arabia.MethodsA national database of BA cases diagnosed between 2000 and 2018 was analyzed. We assessed clearance of jaundice (bilirubin &lt;20 μmol/L) in all cases that underwent Kasai portoenterostomy (KPE). We then estimated survival using the Kaplan–Meier method with endpoints of liver transplantation (LT), death, or survival with native liver (SNL).ResultsBA was diagnosed in 204 infants (106 females; 10% pre-term). The incidence of BA was 1 in 44,365, or 2.254 in 100,000 live births (range, 0.5–4 in 100,000). Polysplenia was diagnosed in 22 cases (11%). The median age at referral was 65 days. A total of 146 children (71.5%) underwent KPE at a median age of 70 days. Clearance of jaundice was achieved in 66 of the 146 (45%) infants. The 10-year SNL after KPE was 25.5%, and the overall 10-year estimated survival was 72.5%. The Kaplan–Meier survival curves for patients undergoing KPE at the age of &lt;60, 61–90, and &gt;90 days showed a SNL rate at 51.6, 33, and 12.5%, respectively, at 5 years (P &lt; 0.001). The 2-, 5-, and 10-year post-LT survival rates were 92.5, 90.6, and 90%, respectively. Undergoing an initial KPE did not impact negatively on the overall LT survival rate when compared to BA cases that underwent primary LT (P = 0.88).ConclusionThe incidence rate of BA in Saudi Arabia is lower than the incidence reported elsewhere. Late referral of BA cases remains a problem in Saudi Arabia; as a result, the SNL rate was lower than reported by other national registries. Hence, national policies devoted to timely referral and earlier age at KPE are needed

Socioeconomic Impacts of Gluten-Free Diet among Saudi Children with Celiac Disease

Purpose: To determine the socio-economic impact of gluten free diet (GFD) on Saudi children and their families Methods: A cross-sectional study was conducted in which an online questionnaire was sent to all families registered in the Saudi celiac patients support group. We included only children (age 18 years of age and younger) with biop-sy-confirmed celiac disease (CD).Results: A total of 113 children were included in the final analysis, the median age was 9.9 years; 62.8% were females. One hundred (88.5%) of the participating families reported that GFD food was not easily available in their areas, 17% of them reported that it was not available at all in their area. One hundred and six (93.8%) reported that the price of GFD food was very expensive and 70 (61.9%) families that the diet was heavily affecting their family budget. Significant social difficulties were reported among the participating families and their children including interference with the child’s interaction with other children (49.6%), the families’ ability to attend social gatherings (60.2%), the families’ ability to eat in restaurants (73.5%), and the families’ ability to travel (58.4%). Conclusion: There is significant negative socio-economic impact of GFD on children with CD & their families. Health care providers should be aware of these psycho-social difficulties and be well trained to provide a proper education and psychological support for these patients and their families.Purpose: To determine the socio-economic impact of gluten free diet (GFD) on Saudi children and their families Methods: A cross-sectional study was conducted in which an online questionnaire was sent to all families registered in the Saudi celiac patients support group. We included only children (age 18 years of age and younger) with biop-sy-confirmed celiac disease (CD).Results: A total of 113 children were included in the final analysis, the median age was 9.9 years; 62.8% were females. One hundred (88.5%) of the participating families reported that GFD food was not easily available in their areas, 17% of them reported that it was not available at all in their area. One hundred and six (93.8%) reported that the price of GFD food was very expensive and 70 (61.9%) families that the diet was heavily affecting their family budget. Significant social difficulties were reported among the participating families and their children including interference with the child’s interaction with other children (49.6%), the families’ ability to attend social gatherings (60.2%), the families’ ability to eat in restaurants (73.5%), and the families’ ability to travel (58.4%). Conclusion: There is significant negative socio-economic impact of GFD on children with CD & their families. Health care providers should be aware of these psycho-social difficulties and be well trained to provide a proper education and psychological support for these patients and their families

Variation in inflammatory bowel disease care among saudi pediatric gastroenterologists

Background/Aim: Although international guidelines in inflammatory bowel disease (IBD) management are currently available, variations in IBD care still exist. The aim of this study was to determine the extent of the variation in IBD care among Saudi pediatric gastroenterologists.Materials and Methods: A cross-sectional survey was conducted among all pediatric gastroenterologists who were members of the Saudi Society of Pediatric Gastroenterology, Hepatology, and Nutrition (SASPGHAN) from August 2015 to December 2015. The questionnaire included items on demographic characteristics and utilization of different diagnostic and therapeutic interventions in IBD care. Results: Of the 45 registered pediatric gastroenterologists surveyed, 37 (82%) returned the survey from 20 centers across the country; 75.7% were practicing in tertiary care centers. There was a considerable variation in the use of different diagnostic tests during the initial evaluation of the disease. Utilization of calprotectin assays, magnetic resonance imaging enterography, and bone densitometry seemed to vary the most between physicians practicing at tertiary and secondary care centers. There were statistically significant differences in the prescription of biological therapy between the two groups. Conclusions: We found a considerable variation in the use of different diagnostic and therapeutic interventions in the management of pediatric IBD patients. Such variations could lead to unintended differences in patient outcomes. Implementation of the available evidence-based guidelines may limit such variations and ultimately could improve the quality of IBD care provided

Does vitamin E improve the outcomes of pediatric nonalcoholic fatty liver disease? A systematic review and meta-analysis

Background and Aims: To systemically evaluate the efficacy of adjuvant vitamin E on the outcomes of nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH) in children. Materials and Methods: We searched MEDLINE, PUBMED, EMBASE, the Cochrane Central Register Controlled Trials, and the Cochrane Database of Systematic Reviews over the period between January 1980 and September 2012 for the studies that examined the role of adjuvant vitamin E given at any dose or duration, alone or in combination with other interventions, on the outcome of pediatric NAFLD. The outcomes are alanine aminotransferase (ALT) normalization and histological improvement. Results: Five randomized trials were eligible to be included in our analysis, with a total of 270 participants. There was no statistically significant difference in the effect of adjuvant vitamin E on normalizing serum ALT [risk ratio (RR) =1.18, confidence interval (CI) =0.92-1.53, P = 0.77 for heterogeneity, I 2 = 0%]. Sensitivity analysis showed that using higher doses of vitamin E, a longer duration of therapy or adding vitamin C did not change the effect on the measured outcome. Only two studies looked at histological changes as an outcome. We observed substantial heterogeneity between the two studies. Conclusions: Our meta-analysis did not find a significant effect of adjuvant vitamin E over placebo in normalizing serum ALT. Data on the long-term effect of adjuvant vitamin E on histological improvements in NAFLD patients are still lacking. Larger, well-designed randomized controlled trials (RCTs) in children with histological endpoints are still needed to answer this question

Clinical Characteristics of Celiac Disease and Dietary Adherence to Gluten-Free Diet among Saudi Children

Purpose: To describe the clinical characteristics of celiac disease (CD) among Saudi children and to determine the adherence rate to gluten free diet (GFD) and its determinant factors among them.Methods: A cross-sectional study was conducted, in which all the families registered in the Saudi Celiac Patients Support Group were sent an online survey. Only families with children 18 years of age and younger with biopsy-con-firmed CD were included.Results: The median age of the 113 included children was 9.9 years, the median age at symptom onset was 5.5 years and the median age at diagnosis was 7 years, the median time between the presentation and the final diagnosis was 1 year. Sixty two of the involved children were females. Ninety two percent of the patients were symptomatic at the diagnosis while eight percent were asymptomatic. The commonest presenting symptoms included: chronic abdominal pain (59.3%), poor weight gain (54%), abdominal distention, gases, bloating (46.1%) and chronic diarrhea (41.6%). Sixty percent of the involved children were reported to be strictly adherent to GFD. Younger age at diagnosis and shorter duration since the diagnosis were associated with a better adherence rate. Conclusion: CD has similar clinical presentations among Saudi children compared to other parts of the ward; however, the adherence to GFD is relatively poor. Younger age at diagnosis and shorter duration since the diagnosis were associated with a better adherence rate.Purpose: To describe the clinical characteristics of celiac disease (CD) among Saudi children and to determine the adherence rate to gluten free diet (GFD) and its determinant factors among them.Methods: A cross-sectional study was conducted, in which all the families registered in the Saudi Celiac Patients Support Group were sent an online survey. Only families with children 18 years of age and younger with biopsy-con-firmed CD were included.Results: The median age of the 113 included children was 9.9 years, the median age at symptom onset was 5.5 years and the median age at diagnosis was 7 years, the median time between the presentation and the final diagnosis was 1 year. Sixty two of the involved children were females. Ninety two percent of the patients were symptomatic at the diagnosis while eight percent were asymptomatic. The commonest presenting symptoms included: chronic abdominal pain (59.3%), poor weight gain (54%), abdominal distention, gases, bloating (46.1%) and chronic diarrhea (41.6%). Sixty percent of the involved children were reported to be strictly adherent to GFD. Younger age at diagnosis and shorter duration since the diagnosis were associated with a better adherence rate. Conclusion: CD has similar clinical presentations among Saudi children compared to other parts of the ward; however, the adherence to GFD is relatively poor. Younger age at diagnosis and shorter duration since the diagnosis were associated with a better adherence rate

Does Adjuvant Steroid Therapy Post-Kasai Portoenterostomy Improve the Outcome of Biliary Atresia? A Systematic Review and Meta-Analysis

BACKGROUND: The role of adjuvant steroid therapy in the postoperative management of patients with biliary atresia (BA) is unclear