Original ResearchFull Report: Gut MicrobiotaBiogeographic Variation and Functional Pathways of the Gut Microbiota in Celiac Disease
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Study Design and Patient Population
Adult patients attending the McMaster University Celiac Disease Clinic with an indication to undergo an upper gastrointestinal endoscopy were recruited for this study. CeD diagnosis (N = 24) was based on a positive transglutaminase-2 (TG2) test using the QUANTA Lite R h-tTG IgA enzyme-linked immunosorbent assay (Inova Diagnostics) or, in the case of IgA deficiency, with IgG deamidated gliadin peptide antibodies (Inova Diagnostics) and confirmed by means of duodenal biopsies assessed by a
Sampling Location Is a Key Determinant of Microbiota Composition in Celiac Disease
Microbiota composition was analyzed in duodenal aspirates, duodenal biopsies, and feces from patients with CeD and controls (Figure 1 and Supplementary Figure 1). Unsupervised hierarchical clustering according to sample location revealed gut location as a key determinant of microbiota composition (Figure 1A). This result was supported by β-diversity (weighted UniFrac) analysis, which showed distinct microbiota clustering by sample location (P = .001, R2 = 0.41) (Figure 1B). Permutational
Discussion
The past decades in microbiome research have significantly increased our understanding of microbial influence in CeD risk.41,43 However, as with other complex gastrointestinal conditions,44,45 universal microbiota signatures for CeD have not been found, due in part to the different methodological approaches and sampling site used.20,41 Indeed, most studies have relied on fecal samples, and none have directly compared, in the same population, microbial community differences between feces and
CRediT Authorship Contributions
Marco Constante, PhD (Data curation: Equal; Formal analysis: Equal; Investigation: Equal; Methodology: Equal; Software: Equal; Visualization: Equal; Writing – original draft: Equal).
Josie Libertucci, PhD (Data curation: Equal; Formal analysis: Equal; Investigation: Equal; Methodology: Equal; Software: Equal; Visualization: Equal; Writing – original draft: Equal).
Heather J. Galipeau, PhD (Investigation: Supporting; Resources: Supporting; Visualization: Supporting; Writing – review & editing:
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Data Availability All sequencing data have been deposited in the Sequence Read Archive. The 16S rRNA gene sequencing data from human feces, duodenal aspirates, and biopsy samples (D1, D2, and D3) from patients with celiac disease and controls used in this study can be accessed under BioProject ID PRJNA812940.
Author names in bold designate shared co-first authorship.
Conflicts of interest The authors disclose no conflicts.
Funding This study was funded by a Canadian Institutes of Health Research (CIHR) PJT-168840 awarded to Elena F. Verdu, who also holds a Canada Research Chair (CIHR) Tier 1 in Microbial Therapeutics and Nutrition in Gastroenterology. Josie Libertucci is funded by an IMAGINE-CIHR-Canadian Association of Gastroenterology postdoctoral research fellowship. Maria Ines Pinto-Sanchez research time is supported by an Alternate Funding Plan-Hamilton Academic Health Sciences Organization. Michael G. Surette holds a Canada Research Chair in Interdisciplinary Microbiome Research. PB holds the Richard Hunt-AstraZeneca Chair in Gastroenterology. Alberto Caminero holds a Paul Douglas Chair in Intestinal Research.
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Authors share co-first authorship.