Gut microbiota predicts the diagnosis of ulcerative colitis in Saudi children.

BACKGROUND: Ulcerative colitis (UC) is an immune-mediated chronic inflammatory condition with a worldwide distribution. Although the etiology of this disease is still unknown, the understanding of the role of the microbiota is becoming increasingly strong. AIM: To investigate the predictive power of the gut microbiota for the diagnosis of UC in a cohort of newly diagnosed treatment-naïve Saudi children with UC. METHODS: The study population included 20 children with a confirmed diagnosis of UC and 20 healthy controls. Microbial DNA was extracted and sequenced, and shotgun metagenomic analysis was performed for bacteria and bacteriophages. Biostatistics and bioinformatics demonstrated significant dysbiosis in the form of reduced alpha diversity, beta diversity, and significant difference of abundance of taxa between children with UC and control groups. The receiver operating characteristic curve, a probability curve, was used to determine the difference between the UC and control groups. The area under the curve (AUC) represents the degree of separability between the UC group and the control group. The AUC was calculated for all identified bacterial species and for bacterial species identified by the random forest classification algorithm as important potential biomarkers of UC. A similar method of AUC calculation for all bacteriophages and important species was used. RESULTS: The median age and range were 14 (0.5-21) and 12.9 (6.8-16.3) years for children with UC and controls, respectively, and 40% and 35% were male for children with UC and controls, respectively. The AUC for all identified bacterial species was 89.5%. However, when using the bacterial species identified as important by random forest classification algorithm analysis, the accuracy increased to 97.6%. Similarly, the AUC for all the identified bacteriophages was 87.4%, but this value increased to 94.5% when the important bacteriophage biomarkers were used. CONCLUSION: The very high to excellent AUCs of fecal bacterial and viral species suggest the potential use of noninvasive microbiota-based tests for the diagnosis of unusual cases of UC in children. In addition, the identification of important bacteria and bacteriophages whose abundance is reduced in children with UC suggests the potential of preventive and adjuvant microbial therapy for UC.

Bacterial dysbiosis in newly diagnosed treatment naïve pediatric ulcerative colitis in Saudi Arabia.

BACKGROUND: The role of microbiota in the pathogenesis of ulcerative colitis (UC) has been increasingly recognized. However, most of the reports are from Western populations. In Middle Eastern countries, including Saudi Arabia, little is known about the role of microbiota. Therefore, our aim was to describe the bacterial microbiota profile and signature in pediatric UC in Saudi Arabia. METHODS: Twenty children with UC and 20 healthy controls enrolled in the study gave stool samples. Twenty rectal mucosal samples were taken from UC and 20 from non-UC controls. Inclusion criteria included newly diagnosed and untreated children and lack of antibiotic exposure for at least 6 months before stool collection was required for children with UC and controls. Bacterial deoxyribonucleic acid was extracted and sequenced using shotgun metagenomic analysis. Statistical analysis included Shannon alpha diversity metrics, Bray-Curtis dissimilarity, DESeq2, and biomarker discovery. RESULTS: The demographic characteristics were similar in children with UC and controls. There was a significant reduction in alpha diversity (P = 0.037) and beta diversity in samples from children with UC (P = 0.001). Many taxa were identified with log2 abundance analysis, revealing 110 and 102 species significantly depleted and enriched in UC, respectively. Eleven bacterial species' signatures were identified. CONCLUSIONS: In Saudi Arabian children with UC, we demonstrate a dysbiosis similar to reports from Western populations, possibly related to changes of lifestyle. Microbial signature discovery in this report is an important contribution to research, leading to the development of adjunctive non-invasive diagnostic options in unusual cases of UC.

Clinical profile of functional constipation in Saudi children.

BACKGROUND: Functional constipation (FC) is a common condition in children, and information on the clinical characteristics of FC in Saudi children is scarce. OBJECTIVE: Describe the clinical profile of FC in Saudi children. DESIGN: Retrospective. SETTING: Hospital that provides primary, intermediate and tertiary care. PATIENTS AND METHODS: All children diagnosed with FC according to the Rome IV criteria were included and had at least one follow-up clinic visit. Demographic and clinical data collected from medical records included the age at onset, duration of constipation, clinical features, treatment modalities, and factors associated with clinical response. Descriptive statistics and Pearson's chi-squared test were used in the statistical analysis to see how categorical study variables were linked to clinical response. A P value of ≤.05 was used to report statistical significance. MAIN OUTCOME MEASURE: Compliance and clinical response to polyethylene glycol (PEG) compared with lactulose. SAMPLE SIZE: 370 children from 0.1 to 13 years of age. RESULTS: The median (IQR) age of onset was 4 (5) years and less than one year in 14%. The median (IQR) duration of constipation was 4 months (11) and less than two months in 93/370 (25%). Abdominal pain was the most commonly associated feature (44%). Screening for celiac disease and hypothyroidism was negative. A Fleet enema was the most common disimpaction method (54%) and PEG was the most common maintenance medication (63.4%). PEG was significantly better tolerated (P=.0008) and more effective than lactulose (P<.0001). Compliance was the only variable significantly associated with clinical response. CONCLUSIONS: PEG was better tolerated and more effective than lactulose in our study, a finding in agreement with the literature. Therefore, PEG should be the drug of choice in the initial management of FC in Saudi children. Prospective studies on the causes of noncompliance are needed to improve the response to treatment. LIMITATIONS: The limitations of retrospective design are missing data, recall bias, and hospital-based limitation, such as missing milder cases treated at the outpatient level. However, the sample size of 370 may have minimized these limitations.