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.

Gut virome profile in healthy Saudi children.

Background: The role of viruses is well known in health and disease. The aim of this report was to describe the profile of viruses in the gut of healthy Saudi children. Methods: In 20 randomly selected school age children from Riyadh, stool samples were collected in cryovials and stored at -80° C. At the time of analysis, the samples were sent by express mail in a temperature-controlled container to the laboratory in the USA, Viral DNA was isolated and shotgun metagenomic sequencing was performed. The abundance of each organism was expressed as an average relative percentage across the viral phylogenetic tree from phyla to species. Results: The median age of the children was 11.3 (range 6.8-15.4) years, and 35% were males. Caudovirales were the most abundant bacteriophage order (77%) and Siphoviridae, Myoviridae, and Podoviridae families predominated, accounting for 41%, 25%, and 11%, respectively. Among the viral bacteriophage species, the most abundant were the Enterobacteria phages. Conclusion: The profile and abundance of the gut virome in healthy Saudi children reveal important differences from the literature. Further studies from different populations with larger sample sizes are needed to understand the role of gut viruses in the pathogenesis of disease in general and in the response to fecal microbiota therapy in particular.

Microbiota profile of new-onset celiac disease in children in Saudi Arabia.

BACKGROUND: Intestinal dysbiosis has been reported to be associated with celiac disease (CeD) in Western populations but little is known in other populations who have different dietary lifestyle and genetic background. The purpose of this study was to determine whether a different microbiota profile is associated with CeD in children in Saudi Arabia. RESULTS: Forty children with CeD, 20 healthy controls, and 19 non-CeD controls were enrolled. The median age at diagnosis was 10.3, 11.3 and 10.6 years in children with CeD, fecal, and mucosal control groups, respectively. Significant differences in microbial composition between children with CeD and controls both at fecal and mucosal level were identified. Fecal samples were more diverse and richer in bacteria as compared with mucosal samples. Proteobacteria were more abundant in duodenal mucosal samples and Firmicutes and Bacteroides were more abundant in stools. The abundance of many taxa was significantly different between children with CeD and non-CeD controls. In mucosal samples, Bifidobacterium angulatum (unadjusted p = 0.006) and Roseburia intestinalis (unadjusted p = 0.031) were examples of most significantly increased species in children with CeD and non-CeD controls, respectively. In fecal samples, there were 169 bacterial species with significantly different abundance between children with CeD and non- CeD controls. CONCLUSIONS: To our knowledge, this is the first report on the microbial profile in a non-Western population of children with new onset CeD. The fact that mucosal and fecal samples were collected from newly diagnosed children with CeD on normal gluten-containing diet suggests strong association between the identified bacteria and CeD. The identification of many unreported bacterial species significantly associated with CeD, indicates the need for further studies from different populations to expand our understanding of the role of bacteria in the pathogenesis of CeD, hopefully leading to the discovery of new adjuvant treatment options.

Intestinal microbiota profile in healthy Saudi children: The bacterial domain.

Background: Knowledge of microbiota in health is essential for clinical research on the role of microbiota in disease. We aimed to characterize the intestinal microbiota in healthy Saudi children. Methods: In this community-based study, stool samples were collected from a randomly selected sample of 20 healthy school children of Saudi origin. The samples were frozen at -80°C till analysis. Bacterial DNA was isolated and libraries were prepared using the Illumina Nextera XT library preparation kit. Unassembled sequencing reads were directly analyzed and quantified for each organism's relative abundance. The abundance for each organism was calculated and expressed as the average relative percentage from phyla to species. Results: The median age was 11.3 (range 6.8-15.4) years, and 35% of them were males. The three most abundant phyla were Firmicutes, Bacteroidetes, and Actinobacteria accounting for 49%, 26%, and 24%, respectively. The most abundant genera included Bifidobacterium, Bacteroides, and Blautia accounting for 18.9%, 12.8%, and 8.2%, respectively. Finally, the most abundant species included 14 species belonging to the genus Bacteroides and nine species belonging to Bifidobacterium. Conclusions: The abundance of intestinal microbiome in healthy Saudi children is different from that of other populations. Further studies are needed to understand the causes of variation between populations, which might lead to new preventive methods and treatment strategies of diseases caused by microbial dysbiosis.

Viral dysbiosis in children with new-onset celiac disease.

Viruses are common components of the intestinal microbiome, modulating host bacterial metabolism and interacting with the immune system, with a possible role in the pathogenesis of immune-mediated diseases such as celiac disease (CeD). The objective of this study was to characterize the virome profile in children with new-onset CeD. We used metagenomic analysis of viral DNA in mucosal and fecal samples from children with CeD and controls and performed sequencing using the Nextera XT library preparation kit. Abundance log2 fold changes were calculated using differential expression and linear discriminant effect size. Shannon alpha and Bray-Curtis beta diversity were determined. A total of 40 children with CeD and 39 controls were included. We found viral dysbiosis in both fecal and mucosal samples. Examples of significantly more abundant species in fecal samples of children with CeD included Human polyomavirus 2, Enterobacteria phage mEpX1, and Enterobacteria phage mEpX2; whereas less abundant species included Lactococcus phages ul36 and Streptococcus phage Abc2. In mucosal samples however, no species were significantly associated with CeD. Shannon alpha diversity was not significantly different between CeD and non-CeD groups and Bray-Curtis beta diversity showed no significant separation between CeD and non-CeD samples in either mucosal or stool samples, whereas separation was clear in all samples. We identified significant viral dysbiosis in children with CeD, suggesting a potential role in the pathogenesis of CeD indicating the need for further studies.

Fungal Dysbiosis in Children with Celiac Disease.

BACKGROUND: Although intestinal fungi are known to interact with the immune system, the relationship between intestinal fungi and childhood celiac disease (CeD), an immune-mediated condition, has rarely been reported. AIMS: The aim of this study was to describe gut fungal profiles in a cohort of children with new-onset CeD. METHODS: Mucosal and fecal samples were collected from children with CeD and controls and subjected to metagenomics analysis of fungal microbiota communities. DNA libraries were sequenced using Illumina HiSeq platform 2 × 150 bp. Bioinformatic analysis was performed to quantify the relative abundance of fungi. Shannon alpha diversity metrics and beta diversity principal coordinate (PCo) analyses were calculated, and DESeq tests were performed between celiac and non-celiac groups. RESULTS: Overall more abundant taxa in samples of children with CeD included Tricholomataceae, Saccharomycetaceae, Saccharomycetes Saccharomyces cerevisiae, and Candida, whereas less abundant taxa included Pichiaceae, Pichia kudriavzevii, Pneumocystis, and Pneumocystis jirovecii. Alpha diversity between CeD and control individuals did not differ significantly, and beta diversity PCo analysis showed overlap of samples from CeD and controls for both fecal or mucosal samples; however, there was a clear separation between mucosal and fecal overall samples CONCLUSIONS: We report fungal dysbiosis in children with CeD, suggesting a possible role in the pathogenesis of CeD. Further larger, controlled, prospective and longitudinal studies are needed to verify the results of this study and clarify the functional role of fungi in CeD.

Congenital hepatic fibrosis in a child with Prader-Willi syndrome: a novel association.

Prader-Willi syndrome (PWS) is a rare genetic disorder caused by deletion or unexpression of the chromosome 15 (q 11-13). Symptomatologies include hypotonia, hyperphagia, cognitive impairment, and characteristic dysmorphic profile. Here, we report a 4-year-old boy with PWS who presented with complications of congenital hepatic fibrosis. The uniparental heterodisomy makes it unlikely that the hepatic fibrosis was caused by unmasking of a recessive mutation on the maternal chromosome 15 although we cannot exclude the possibility of a recessively inherited mutation elsewhere given the parental consanguinity. This is the first report of congenital hepatic fibrosis in PWS.