Biogeographic variation and functional pathways of the gut microbiota in celiac disease

CONSTANTE M; LIBERATORE J; GALIPEAU H; SZAMOSI JC1; RUEDA G; MIRANDA PM; PINTO-SANCHEZ I; SOUTHWARD CM; ROSSI L; FONTES ME; CHIRDO FG; SURETTE MG; BERCIK P; CAMINERO A; VERDU E

GASTROENTEROLOGY

W B SAUNDERS CO-ELSEVIER INC

Lugar: Philadelphia; Año: 2022

0016-5085

Background & Aims: Genes and gluten are necessary but insufficient to cause celiac disease (CeD). Altered gut microbiota has been implicated as an additional risk factor. Variability in sampling site may confound interpretation and mechanistic insight, as CeD affects primarily the small intestine. Thus, we characterized CeD microbiota along the duodenum and in feces and verified functional impact in gnotobiotic mice. Methods: We used 16S rRNA gene sequencing (Illumina) and predicted gene function (PICRUSt2) in duodenal biopsies (D1, D2 and D3), aspirates, and stool from active CeD patients and controls. CeD alleles were determined in consented participants. A subset of duodenal samples stratified according to similar CeD risk genotypes (controls DQ2-/- or DQ2+/- and CeD DQ2+/-), were used for further analysis and to colonize germ-free mice for gluten metabolism studies. Results: Microbiota composition and predicted function in CeD was largely determined by intestinal location. In the duodenum, but not stool, there was higher abundance of Escherichia coli (D1), Prevotella salivae (D2), and Neisseria (D3) in CeD versus controls. Predicted bacterial protease and peptidase genes were altered in CeD and impaired gluten degradation was detected only in mice colonized with CeD microbiota.Summary and Conclusions: Our results show luminal and mucosal microbial niches along the gut in CeD. We identify novel microbial proteolytic pathways involved in gluten detoxification that are impaired in CeD, but not in controls carrying DQ2, suggesting association with active duodenal inflammation. Sampling site should be considered a cofounding factor in microbiome studies in CeD.