دورية أكاديمية
Biogeographic Variation and Functional Pathways of the Gut Microbiota in Celiac Disease.
العنوان: | Biogeographic Variation and Functional Pathways of the Gut Microbiota in Celiac Disease. |
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المؤلفون: | Constante M; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Libertucci J; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Galipeau HJ; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Szamosi JC; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Rueda G; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Miranda PM; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Pinto-Sanchez MI; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Southward CM; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Rossi L; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Fontes ME; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Chirdo FG; Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Instituto de Estudios Inmunológicos y Fisiopatológicos, Universidad Nacional de La Plata-National Scientific and Technical Research Council, La Plata, Argentina., Surette MG; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Ontario, Canada., Bercik P; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Caminero A; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada. Electronic address: acamine@mcmaster.ca., Verdu EF; Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada. Electronic address: verdue@mcmaster.ca. |
المصدر: | Gastroenterology [Gastroenterology] 2022 Nov; Vol. 163 (5), pp. 1351-1363.e15. Date of Electronic Publication: 2022 Jul 08. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: W.B. Saunders Country of Publication: United States NLM ID: 0374630 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0012 (Electronic) Linking ISSN: 00165085 NLM ISO Abbreviation: Gastroenterology Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Philadelphia, PA : W.B. Saunders Original Publication: Baltimore. |
مواضيع طبية MeSH: | Celiac Disease*/complications , Gastrointestinal Microbiome*, Mice ; Animals ; RNA, Ribosomal, 16S/genetics ; Glutens/metabolism ; Peptide Hydrolases |
مستخلص: | 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 primarily affects 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 patients with active CeD 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 vs controls. Predicted bacterial protease and peptidase genes were altered in CeD and impaired gluten degradation was detected only in mice colonized with CeD microbiota. Conclusions: Our results showed luminal and mucosal microbial niches along the gut in CeD. We identified novel microbial proteolytic pathways involved in gluten detoxification that are impaired in CeD but not in controls carrying DQ2, suggesting an association with active duodenal inflammation. Sampling site should be considered a confounding factor in microbiome studies in CeD. (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.) |
معلومات مُعتمدة: | PJT-168840 Canada CIHR |
فهرسة مساهمة: | Keywords: Celiac Disease; Duodenum; Gnotobiotic Mice; Gut Microbiota; Proteases |
المشرفين على المادة: | 0 (RNA, Ribosomal, 16S) 8002-80-0 (Glutens) EC 3.4.- (Peptide Hydrolases) |
تواريخ الأحداث: | Date Created: 20220710 Date Completed: 20221025 Latest Revision: 20221104 |
رمز التحديث: | 20240628 |
DOI: | 10.1053/j.gastro.2022.06.088 |
PMID: | 35810781 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1528-0012 |
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DOI: | 10.1053/j.gastro.2022.06.088 |