Gluten-Free Diet Induces Changes in Intestinal Microbiota of Children With Celiac Disease

Celiac disease symptoms vary from person to person. Digestive symptoms are more common in infants and young children and may include abdominal pain, chronic diarrhea, vomiting, constipation and weight loss.
Investigators characterized the gut microbiota of children with celiac disease to collect data on the determinants of the microbiota likely to change in children following a gluten-free diet.

Adherence to a gluten-free diet (GFD) appeared to alter intestinal microbiota in children with celiac disease (CD); however, specific bacteria that served as “biomarkers” for the disease sustained, according to findings from a cross-sectional prospective study published in Gastroenterology. Further study of these microbes is needed to determine whether they contribute to the pathogenesis of celiac disease, the investigators said.

The study authors obtained 167 fecal samples from 141 children with CD seen at the Royal Hospital for Children in Glasgow. Patient makeup was as follows: 20 children had new-onset CD; 45, CD treated with a GFD; and 57, no CD. The remaining 19 patients were the unaffected siblings of a patient with CD. Fecal samples were collected at baseline and at 6 and 12 months after initiation of a GFD diet in 13 children with new-onset CD. The samples were analyzed by 16S ribosomal RNA sequencing; diet-related metabolites were assessed by gas chromatography.

Children with untreated CD (n=20) were found to have significantly higher tissue transglutaminase immunoglobulin A antibody titer (mean, 64.8; standard error of the mean [SEM], 13.3 U/mL) compared with children with treated CD (n=45; mean, 7.9; SEM, 3.0 U/mL; P <.0001). Healthy control patients had the highest Pediatric Quality of Life Inventory-Gastrointestinal Scale (PedsQL-GS) scores (mean, 91.4; SEM, 1.7) followed by unaffected siblings (mean, 88.2; SEM, 2.9), and children with treated CD (mean, 77.5; SEM, 2.7; P <.0001). Children with untreated CD reported the lowest PedsQL-GS scores (mean, 57.1; SEM, 4.8, P <.0001).

“Microbiota a diversity did not differ among groups,” the investigators said. However, the operational taxonomic unit (OTU) community structure (b diversity) differed significantly (Overall Bray-Curtis dissimilarity index, 2.8%; P =.025; overall UniFrac distance, 2.5%; P =.027). A subset of 13 microbes explained 92.3% of the taxonomic variation.

Comparing patients with untreated CD with healthy control patients led to the identification of 1033 distinct OTUs, 3% of which differed significantly between the 2 groups. The abundance of these differentially expressed bacterial taxon was lower in children with CD. A single bacterium, Alistipes, positively correlated with PedsQL-GS scores.

“Of these 31 discriminatory OTUs, only the abundance of OTU_1054 Alistipes correlated positively with PedsQL-GS score, suggesting the remaining 30 discriminatory OTUs were less likely to be explained by differences in [gastrointestinal] symptoms between the 2 groups,” the study authors observed.

The investigators next assessed the effect of a GFD on CD microbiota. To facilitate the analysis, the study authors compared healthy control patients with children with treated CD. Twenty-nine of 1082 OTUs (3%) were found to present at a different abundance in the control and treated CD subgroups. Thirteen of the 29 OTUs were increased in the CD subset. Of these 13 differentially expressed taxon, 10 (77%) were “significantly higher” in treated vs untreated celiac disease group, “suggesting that treatment with a GFD influences these taxa independently of disease status,” according to the study authors.

Among patients with treated and untreated CD, 1082 distinct taxonomic units were identified, 5% of which “differed significantly” between groups. Most (94%) differentially expressed OTUs were significantly more abundant among children with CD treated with a GFD vs untreated patients with CD.

From these comparisons, the investigators identified a panel of 11 OTUs that composed a microbial signature specific to CD and had high diagnostic potential (area under the curve, 0.789; P <.001). The 2 most robust taxa were Clostridium sensu stricto 1 and Ruminococcus.

In addition to altered gut microbiota, children on a GFD demonstrated non-significant decreases in isovaleric acid (P =.052), butyric acid (P =.053), and isobutyric acid (P =.063) concentrations in their fecal samples.

This analysis was limited by the loss of patients from the untreated CD group at follow-up. The “modest sample size” of the prospective group was another limiting factor. Nevertheless, the researchers surmised that gut microbiota may be a diagnostic tool for CD: “In conclusion, we identified a set of bacteria that may comprise another important environmental factor in the pathogenesis of CD and that warrant further research,” they stated.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of the authors’ disclosures.


Zafeiropoulou K, Nichols B, Mackinder M, et al. Alterations in intestinal microbiota of children with celiac disease at the time of diagnosis and on a gluten-free diet. Gastroenterology. 2020;159(6):2039-2051.e20. doi:10.1053/j.gastro.2020.08.007