Lack of Effect of Gluten Challenge on Fecal Microbiome in Patients With Celiac Disease and Non-Celiac Gluten Sensitivity

INTRODUCTION: Celiac disease (CD) may be associated with gut microbial dysbiosis. Whether discrete gluten exposure in subjects with well-controlled disease on a gluten-free diet impacts the gut microbiome is unknown and may have implications for understanding disease activity and symptoms. We conducted a prospective study to evaluate the impact of gluten exposure on the gut microbiome in patients with CD and nonceliac gluten sensitivity (NCGS). METHODS: Subjects with CD (n = 9) and NCGS (n = 8) previously on a gluten-free diet were administered a 14-day gluten challenge (5 g of gluten per day) and compared with controls (n = 8) on a usual gluten-containing diet. Stool was collected for fecal microbiome analysis using 16S rRNA gene and metagenomic sequencing before, during, and after the gluten challenge. Symptoms were assessed using 2 validated clinical scales. RESULTS: Among subjects with CD and NCGS, there were no significant fecal microbial changes in response to gluten challenge. Gut microbiome composition differed among controls, subjects with CD, and subjects with NCGS at baseline, and these differences persisted despite gluten exposure. Gastrointestinal and general health symptoms reported by subjects with CD and NCGS were worst in the middle of gluten challenge and lessened by its end, with no consistent associations with gut microbiome composition. DISCUSSION: Pre-existing fecal microbiome diversity was unaffected by gluten challenge in adult subjects with CD and NCGS. These findings suggest that current microbiome status is unrelated to current disease activity and disease severity.