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

Emerging inflammatory bowel disease in saudi outpatients: A report of 693 cases

Background/Aim: Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology and considered traditionally as a disease of the western world. Recently, rising trends have been observed in countries previously known to have a low prevalence and incidence. The aim of this study is to collect epidemiological data on IBD outpatients and to add data from the Kingdom of Saudi Arabia (KSA) to the available IBD literature. Patients and Methods: The medical records of 693 Saudi patients with IBD over a period of 17 years, between 1993 and 2009, were reviewed. The demographic and clinical data and methods of diagnosis were retrieved. Results: The total number of patients in this cohort was 693. It constituted 238 (34.3%) ulcerative colitis (UC) and 455 (65.7%) Crohn′s disease (CD) patients. UC was steady throughout the years, whereas only 1.2 CD patients were diagnosed per year in the first 11 years, and 73.7 per year in the last six years. The median age of UC patients was 34 years, ranging from 10 to 80 years with a peak between 21 and 40 years and in CD it was 27 years, ranging from 11 to 73 years with a peak between 11 and 30 years. There was a male preponderance of 1.5:1 and 2:1, respectively. The rest of the data is discussed in this study. Conclusion: IBD is no longer a rare disease in KSA. UC is in a steady state, whereas CD is increasing significantly and far outnumbering UC

Formol-ether concentration method in the diagnosis of active schistosoma mansoni in patients with detectable IHA

Schistosomiasis is a world wide human infection. In Saudi Arabia there are multiple endemic foci. Various methods have been used to diagnose Schistosoma mansoni. We studied 1410 patients coming from S. mansoni endemic areas with detectable antibodies by indirect hemagglutination (IHA). Stool specimens were tested for S. mansoni ova by direct smear and formol-ether concentration (FEC) methods. The objective of the study was to identify patients with active schistosomiasis using FEC method and a single direct smear. Twenty percent of IHA positive patients had active infection detected by FEC, while a single direct stool smear diagnosed only 2.4&#x0025; (P&#60; 0.0001). The percentage of positive FEC was significantly increasing in linear trend with IHA level. This trend wasn&#x2032;t observed with direct smear examination. The current data suggest that FEC is helpful to diagnose active schistosomiasis, therefore it is recommended in IRA positive individuals

<i>Crohn&#x2032;s disease</i> in a Saudi outpatient population: Is it still rare?

<b>Background/Aim:</b> To determine the epidemiology of Crohn&#x2032;s disease (CD) in an outpatient clinic and compare it with data previously reported from different centers in the Kingdom of Saudi Arabia and outside. <b> Materials and Methods:</b> The medical records of all patients with CD seen in the clinic in the period from January 1993 through December 2007 were reviewed. The demographic, clinical data and methods of diagnosis were retrieved. <b> Results:</b> Over a period of 15 years, we saw 133 Saudi patients with CD. They were predominantly young, with a median age of 26.2 years and male preponderance (2.3:1). The final diagnosis was established within 1 week of presentation in 47&#x0025; of the patients. The leading symptoms were abdominal pain (88&#x0025;), diarrhea (70&#x0025;), bloating (61&#x0025;), rectal bleeding (50&#x0025;), weight loss (33&#x0025;), constipation (24&#x0025;) and perianal disease (23&#x0025;). The diagnosis was established by endoscopy and histopathology. Ileocecal involvement was encountered in 40&#x0025; of the patients. <b> Conclusion: </b> From the current study, it is obviously possible to diagnose a large proportion of patients with CD in a gastroenterology outpatient clinic. The data revealed a strikingly increased incidence of CD in a mainly young Saudi population in the past few years

Characteristics of Pediatric Crohn’s Disease in Saudi Children: A Multicenter National Study

Background and Aims. Crohn’s disease (CD) is an evolving disease in KSA. Little is known about its characteristics in the Saudi population. The aims of this study were to describe the characteristics of Saudi children with CD and to determine whether the characteristics of CD in KSA are different from those seen in Western countries. Methods. In this study, children younger than eighteen years of age diagnosed with CD between January 2003 and December 2012 were included. Results. Of 330 patients identified, 186 (56.4%) were males. The median age at diagnosis was 15.8 years. A positive family history for IBD in first-degree relatives occurred in 13.6% of patients. The most common symptoms were abdominal pain (84.2%), weight loss (75.2%), and diarrhea (71.8%). The main disease location was ileocolonic (42.1%) and the main disease behavior was nonstricturing and nonpenetrating (63.6%). Perianal involvement was seen in 60 (18.2%) patients. Laboratory findings revealed anemia in 57.9% of patients, low albumin in 34.5%, and high CRP in 39.4%. Conclusions. Saudi children with CD have lower frequency of first-degree relatives with IBD, lower prevalence of early onset disease, longer diagnostic delay, higher prevalence of growth failure, and greater frequency of stricturing and penetrating disease behavior compared to Western patients

Impact of pediatric inflammatory bowel disease on linear growth: Data from a national cohort study in Saudi Arabia

Background/Aim: Linear growth impairment (LGI) is one of the most important features peculiar to children with inflammatory bowel disease (IBD). The aim of this report is to define the impact of IBD on the linear growth of children in the Kingdom of Saudi Arabia (KSA). Setting and Design: Multicenter retrospective study. Patients and Methods: Data from a cohort of newly- diagnosed children with IBD from 2003 to 2012 were analyzed retrospectively. The diagnosis of IBD was confirmed in accordance with the published criteria. Length/height for age was measured at diagnosis. The World Health Organization (WHO) reference was used and LGI was defined by length/height for age <-2 standard deviation. Chi-square test was used to test the significance of estimates and a P < 0.05 was considered significant. Results: There were 374 children from 0.33 to 16 years of age, including 119 ulcerative colitis (UC) (32%), and 255 Crohn's disease (CD) (68%) patients. The prevalence of LGI was 26%, 28%, and 21% in IBD, CD, and UC, respectively. In children below 10 years, LGI was significantly more common in CD (P = 0.010), while in UC children, it was more common in older children (P = 0.011). Conclusion: This study demonstrates a prevalence of LGI consistent with that reported in the literature, but higher in CD children with early onset (<10 years) and in older children with UC, underscoring the importance of monitoring growth in children with IBD in the Saudi population. Prospective studies are needed to define the impact of IBD on growth velocity, puberty, and final adult stature

Microbiota profile in new-onset pediatric Crohn’s disease: data from a non-Western population

Abstract Background The role of microbiota in Crohn’s disease (CD) is increasingly recognized. However, most of the reports are from Western populations. Considering the possible variation from other populations, the aim of this study was to describe the microbiota profile in children with CD in Saudi Arabia, a non-Western developing country population. Results Significantly more abundant genera in children with CD included Fusobacterium, Peptostreptococcus, Psychrobacter, and Acinetobacter; whereas the most significantly-depleted genera included Roseburia, Clostridium, Ruminococcus, Ruminoclostridium, Intestinibacter, Mitsuokella, Megasphaera, Streptococcus, Lactobacillus, Turicibacter, and Paludibacter. Alpha diversity was significantly reduced in stool (p = 0.03) but not in mucosa (p = 0.31). Beta diversity showed significant difference in community composition between control and CD samples (p = 0.03). Conclusion In this developing country, we found a pattern of microbiota in children with CD similar to Western literature, suggesting a role of recent dietary lifestyle changes in this population on microbiota structure

Fungal microbiota profile in newly-diagnosed treatment-naïve children with Crohn's disease

BACKGROUND & AIMS: although increasing evidence suggests a role for fungi in inflammatory bowel disease (IBD), data are scarce and mostly from adults. Our aim was to define the characteristics of fungal microbiota in newly-diagnosed treatment-naïve children with Crohn disease (CD). METHODS: The children referred for colonoscopy were prospectively enrolled in the study at King Khalid University Hospital, King Saud University and Al Mofarreh Polyclinics in Riyadh. Tissue and stool samples were collected and frozen till sequencing analysis. The children with confirmed CD diagnosis were designated as cases and the others as non- IBD controls. 78 samples were collected from 35 children (15 CD and 20 controls). Statistical analysis was performed to investigate CD associations and diversity. RESULTS: CD-associated fungi varied with the level of phylogenetic tree. There was no significant difference in abundance between normal and inflamed mucosa. Significantly abundant CD-associated taxa included Psathyrellaceae (p=0.01), Cortinariaceae (p= 0.04), Psathyrella (p= 0.004), and Gymnopilus (p=0.03).Monilinia was significantly depleted (p=0.03), whereas other depleted taxa, although not statistically significant, included Leotiomycetes (p= 0.06), Helotiales (p=0.08), Sclerotiniaceae (p=0.07). There was no significant difference in fungal diversity between CD and controls. CONCLUSIONS: We report highly significant fungal dysbiosis in newly diagnosed treatment naïve CD children. Depleted and more abundant taxa suggest anti-inflammatory and proinflamatory potentials respectively. Further studies with larger sample size including functional analysis are needed to clarify the significance of the fungal community in the pathogenesis of CD