Alterations in Intestinal Microbiota of Children With Celiac Disease at Time of Diagnosis and on a Gluten-Free Diet

ABSTRACT Background & Aims It is not clear whether alterations in the intestinal microbiota of children with celiac disease cause the disease or are a result of disease and/or its treatment with gluten-free diet (GFD). Methods We obtained 167 fecal samples from 141 children (20 with new-onset celiac disease, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with celiac disease) in Glasgow, Scotland. Samples were analyzed by 16S rRNA sequencing and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 of the children with new-onset CD after 6 and 12 months on GFD. Relationships between microbiota with diet composition, gastrointestinal function, and biomarkers of GFD compliance were explored. Results Microbiota α diversity did not differ among groups. Microbial dysbiosis was not observed in children with new-onset celiac disease. In contrast, 2.8% (Bray-Curtis dissimilarity index, P=.025) and 2.5% (UniFrac distances, P=.027) of the variation in microbiota composition could be accounted for by the GFD. Between 3% to 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to celiac disease with high diagnostic probability. Most of the operational taxonomic units that differed between patients on GFD with new-onset celiac disease vs healthy children were associated with nutrient and food group intake (from 75% to 94%), and with biomarkers of gluten ingestion. Fecal levels of butyrate and ammonia decreased during the GFD. Conclusions Although several alterations in the intestinal microbiota of children with established celiac disease appear to be effects of a GFD, there are specific bacteria that are distinct biomarkers of celiac disease. Studies are needed to determine whether these bacteria contribute to pathogenesis of celiac disease.