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Influence of Crohn's disease related polymorphisms in innate immune function on ileal microbiome.
- Source :
-
PloS one [PLoS One] 2019 Feb 28; Vol. 14 (2), pp. e0213108. Date of Electronic Publication: 2019 Feb 28 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- We have previously identified NOD2 genotype and inflammatory bowel diseases (IBD) phenotype, as associated with shifts in the ileal microbiome ("dysbiosis") in a patient cohort. Here we report an integrative analysis of an expanded number of Crohn's disease (CD) related genetic defects in innate immune function (NOD2, ATG16L1, IRGM, CARD9, XBP1, ORMDL3) and composition of the ileal microbiome by combining the initial patient cohort (Batch 1, 2005-2010, n = 165) with a second consecutive patient cohort (Batch 2, 2010-2012, n = 118). These combined patient cohorts were composed of three non-overlapping phenotypes: 1.) 106 ileal CD subjects undergoing initial ileocolic resection for diseased ileum, 2.) 88 IBD colitis subjects without ileal disease (predominantly ulcerative colitis but also Crohn's colitis and indeterminate colitis, and 3.) 89 non-IBD subjects. Significant differences (FDR < 0.05) in microbiota were observed between macroscopically disease unaffected and affected regions of resected ileum in ileal CD patients. Accordingly, analysis of the effects of genetic and clinical factors were restricted to disease unaffected regions of the ileum. Beta-diversity differed across the three disease categories by PERMANOVA (p < 0.001), whereas no significant differences in alpha diversity were noted. Using negative binomial models, we confirmed significant effects of IBD phenotype, C. difficile infection, and NOD2 genotype on ileal dysbiosis in the expanded analysis. The relative abundance of the Proteobacteria phylum was positively associated with ileal CD and colitis phenotypes, but negatively associated with NOD2R genotype. Additional associations with ORMDL3 and XBP1 were detected at the phylum/subphylum level. IBD medications, such as immunomodulators and anti-TNFα agents, may have a beneficial effect on reversing dysbiosis associated with the IBD phenotype. Exploratory analysis comparing microbial composition of the disease unaffected region of the resected ileum between 27 ileal CD patients who subsequently developed endoscopic recurrence within 6-12 months versus 34 patients who did not, suggested that microbial biomarkers in the resected specimen helped stratify patients with respect to risk of post-surgical recurrence.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Case-Control Studies
Cohort Studies
Crohn Disease immunology
Digestive System Surgical Procedures
Dysbiosis genetics
Dysbiosis immunology
Dysbiosis microbiology
Female
Gastrointestinal Microbiome genetics
Genotype
Humans
Ileum surgery
Male
Membrane Proteins genetics
Membrane Proteins immunology
Middle Aged
Nod2 Signaling Adaptor Protein genetics
Nod2 Signaling Adaptor Protein immunology
Polymorphism, Genetic
RNA, Ribosomal, 16S genetics
X-Box Binding Protein 1 genetics
Young Adult
Crohn Disease genetics
Crohn Disease microbiology
Gastrointestinal Microbiome immunology
Ileum microbiology
Immunity, Innate genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 14
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 30818349
- Full Text :
- https://doi.org/10.1371/journal.pone.0213108