Alterations in intestinal microbiota of children with celiac disease at the time of diagnosis and on a gluten-free diet

TY - JOUR

T1 - Alterations in intestinal microbiota of children with celiac disease at the time of diagnosis and on a gluten-free diet

AU - Zafeiropoulou, Konstantina

AU - Nichols, Ben

AU - Mackinder, Mary

AU - Biskou, Olga

AU - Rizou, Eleni

AU - Karanikolou, Antonia

AU - Clark, Clare

AU - Buchanan, Elaine

AU - Cardigan, Tracey

AU - Duncan, Hazel

AU - Wands, David

AU - Russell, Julie

AU - Hansen, Richard

AU - Russell, Richard K.

AU - McGrogan, Paraic

AU - Edwards, Christine A.

AU - Ijaz, Umer Z.

AU - Gerasimidis, Konstantinos

N1 - Funding Information: Funding This study was funded by Nutricia Research Foundation. Dr Ben Nichols was funded by a grant from the Biotechnology and Biological Sciences Research Council (BB/R006539/1) and The Catherine McEwan Foundation. Publisher Copyright: © 2020 The Authors

PY - 2020/12

Y1 - 2020/12

N2 - Background And Aims: It is not clear whether alterations in the intestinal microbiota of children with celiac disease (CD) cause the disease or are a result of disease and/or its treatment with a gluten-free diet (GFD). Methods: We obtained 167 fecal samples from 141 children (20 with new-onset CD, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with CD) in Glasgow, Scotland. Samples were analyzed by 16S ribosomal RNA sequencing, and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 children with new-onset CD after 6 and 12 months on a 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 CD. 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 explained by the GFD. Between 3% and 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to CD with high diagnostic probability. Most operational taxonomic units that differed between patients on a GFD with new-onset CD 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 CD appear to be effects of a GFD, specific bacteria were found to be distinct biomarkers of CD. Studies are needed to determine whether these bacteria contribute to pathogenesis of CD.

AB - Background And Aims: It is not clear whether alterations in the intestinal microbiota of children with celiac disease (CD) cause the disease or are a result of disease and/or its treatment with a gluten-free diet (GFD). Methods: We obtained 167 fecal samples from 141 children (20 with new-onset CD, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with CD) in Glasgow, Scotland. Samples were analyzed by 16S ribosomal RNA sequencing, and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 children with new-onset CD after 6 and 12 months on a 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 CD. 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 explained by the GFD. Between 3% and 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to CD with high diagnostic probability. Most operational taxonomic units that differed between patients on a GFD with new-onset CD 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 CD appear to be effects of a GFD, specific bacteria were found to be distinct biomarkers of CD. Studies are needed to determine whether these bacteria contribute to pathogenesis of CD.

KW - Microbiome

KW - OTU

KW - Pediatric

KW - Short-chain Fatty Acids

UR - https://www.scopus.com/pages/publications/85097386984

U2 - 10.1053/j.gastro.2020.08.007

DO - 10.1053/j.gastro.2020.08.007

M3 - Article

C2 - 32791131

SN - 0016-5085

VL - 159

SP - 2039-2051.e20

JO - Gastroenterology

JF - Gastroenterology

IS - 6

ER -