Low Levels of Detectable Urine and Stool GIPs in Children with Celiac Disease on a Gluten-Free Diet.

Objectives: This study examines the prevalence of detectable gluten immunogenic peptides (GIPs) as a proxy for gluten exposure in children with celiac disease on a gluten-free diet in the United States, as estimated by gluten breakdown products excreted in urine and stool. Methods: Urine and stool samples were collected in 3 settings (home, gastroenterology clinic, and endoscopy) for pediatric participants (ages 6-21 years old) across 2 medical centers. Commercial ELISA assays were used to quantify the GIPs in each sample. Results: GIPs were detected in 4 out of 44 (9.1%) of stool samples and 6 out of 125 (4.8%) of urine samples provided by 84 children. These samples were collected across all settings, and most participants (70%) were asymptomatic at the time of sample collection. For the urine samples collected at the time of endoscopy, all subjects found to have persistent enteropathy had no detectable GIPs (0/12). Discussion: GIPs provide an additional method for screening for gluten exposures in individuals with celiac disease on a gluten-free diet, and may be used across multiple settings. We found a low detection rate of GIPs in children. Our finding of undetectable GIPs in individuals with persistent enteropathy may be expected of a single determination under close observation or represent a lack of gluten exposure within the detection window. More research is needed to understand the dynamics of gluten absorption and excretion in the US pediatric population.

No Increased Risk of Taking Additional Intestinal Mucosal Research Biopsies From the Duodenum During Pediatric Endoscopy.

Studies involving human intestinal tissue are essential for advancing the field of celiac disease (CeD), as diagnosis requires duodenal biopsies. Performing studies in children helps to better understand CeD in this important subpopulation. This study aims to determine the risk in obtaining duodenal research biopsies during pediatric endoscopy. In this retrospective chart review from 2016 to 2022 of 1180 research subjects and controls, there were 18 procedure-related adverse events within 48 hours. Most adverse events were for symptoms of pain and fever. There was no increased risk of adverse events if additional duodenal research biopsies were taken during pediatric endoscopy.

Microbiota and Metabolomic Patterns in the Breast Milk of Subjects with Celiac Disease on a Gluten-Free Diet.

The intestinal microbiome may trigger celiac disease (CD) in individuals with a genetic disposition when exposed to dietary gluten. Research demonstrates that nutrition during infancy is crucial to the intestinal microbiome engraftment. Very few studies to date have focused on the breast milk composition of subjects with a history of CD on a gluten-free diet. Here, we utilize a multi-omics approach with shotgun metagenomics to analyze the breast milk microbiome integrated with metabolome profiling of 36 subjects, 20 with CD on a gluten-free diet and 16 healthy controls. These analyses identified significant differences in bacterial and viral species/strains and functional pathways but no difference in metabolite abundance. Specifically, three bacterial strains with increased abundance were identified in subjects with CD on a gluten-free diet of which one (Rothia mucilaginosa) has been previously linked to autoimmune conditions. We also identified five pathways with increased abundance in subjects with CD on a gluten-free diet. We additionally found four bacterial and two viral species/strains with increased abundance in healthy controls. Overall, the differences observed in bacterial and viral species/strains and in functional pathways observed in our analysis may influence microbiome engraftment in neonates, which may impact their future clinical outcomes.

Gut microbiota in Celiac Disease: microbes, metabolites, pathways and therapeutics.

INTRODUCTION: Current evidence supports a vital role of the microbiota on health outcomes, with alterations in an otherwise healthy balance linked to chronic medical conditions like celiac disease (CD). Recent advances in microbiome analysis allow for unparalleled profiling of the microbes and metabolites. With the growing volume of data available, trends are emerging that support a role for the gut microbiota in CD pathogenesis. AREAS COVERED: In this article, the authors review the relationship between factors such as genes and antibiotic exposure on CD onset and the intestinal microbiota. The authors also review other microbiota within the human body (like the oropharynx) that may play a role in CD pathogenesis. Finally, the authors discuss implications for disease modification and the ultimate goal of prevention. The authors reviewed literature from PubMed, EMBASE, and Web of Science. EXPERT OPINION: CD serves as a unique opportunity to explore the role of the intestinal microbiota on the development of chronic autoimmune disease. While research to date provides a solid foundation, most studies have been case-control and thus do not have capacity to explore the mechanistic role of the microbiota in CD onset. Further longitudinal studies and integrated multi-omics are necessary for investigating CD pathogenesis.