Gluten Challenge Leads to No Significant Changes in Fecal Microbiome Composition in Patients With Celiac Disease and NCGS

Gluten free bread on wooden background
Investigators assessed the effects of short-term gluten exposure on gut microbiome composition in patients with celiac disease and nonceliac gluten sensitivity.

The baseline fecal microbiome diversity in adult patients with celiac disease (CD) and nonceliac gluten sensitivity (NCGS) was unaffected by short-term gluten exposure, according to a study in Clinical and Translational Gastroenterology.

The prospective study compared patients with CD and NCGS who had been on a long-term gluten-free diet and were given a 14-day gluten challenge vs control individuals who remained on a nonrestrictive, gluten-containing diet.

The cohort included 9 patients with CD (median age, 57.9 years; 55.6% women), 8 patients with NCGS (median age, 51.9 years; 100% women), and 8 control individuals (median age, 40.4 years; 50% women). The study included a 2-week lead-in period of usual gluten-free diet, a 2-week gluten challenge in which participants consumed 5 g of gluten per day, and a 2-week follow-up of usual gluten-free diet. Clinical symptom questionnaires and stool samples were collected at 5 timepoints before, during, and after the gluten challenge.

No significant changes were observed in the gut microbiome composition during or after the gluten challenge in the CD or NCGS group. The baseline gut microbiome composition differed among the 3 study groups and continued after the gluten challenge. Alpha diversity did not differ in the 3 groups over time, but beta diversity was significantly different at all timepoints.

The CD and NCGS groups had more severe symptoms compared with control individuals at all timepoints, with a nonsignificant trend towards worsening of some symptoms during the study. Nausea and vomiting were most severe among patients with NCGS throughout the study and increased in patients with CD after gluten exposure.

The gut microbiome composition was also assessed within the CD and NCGS groups in a comparison of patients with high vs low overall symptoms at the end of the gluten challenge. No significant differences were found in alpha or beta diversity between those with high and low overall symptoms in either group.

Study limitations include the small sample size in each study group, which did not include children or adolescents. Additionally, symptom variability was limited. Finally, 4 patients with CD left the study, and thus researchers were unable to evaluate associations between gut microbiome composition and CD in those with the most severe response to gluten.

“Our findings indicate that in people with CD and NCGS on a long-term gluten-free diet, short-term gluten consumption does not alter gut microbiome composition,” stated the investigators. “Gut microbial dysbiosis in patients with established CD or NCGS is unlikely to meaningfully impact disease activity and symptom severity in patients with these conditions.”


Nobel YR, Rozenberg F, Park H, et al. Lack of effect of gluten challenge on fecal microbiome in patients with celiac disease and non-celiac gluten sensitivity. Clin Transl Gastroenterol. 2021;12(12):e00441. doi: 10.14309/ctg.0000000000000441