The Impact of NOD2 Genetic Variants on the Gut Mycobiota in Crohn’s Disease Patients in Remission and in Individuals Without Gastrointestinal Inflammation
| Autor: | Darren Smith, Charlie W. Lees, Nicholas A. Kennedy, Georgina L. Hold, Miles Parkes, Simon H. Bridge, Andrew Nelson, John K Lodge, Chris Probert, Christopher J. Stewart, John C. Mansfield, Christopher A. Lamb, Mark Tremelling |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Crohn’s disease Mycobiota Genotype Nod2 Signaling Adaptor Protein Cryptococcus gut mycobiota Pathogenesis Feces Crohn Disease Eccojc/1140 NOD2 medicine Humans NOD2 genotype Internal transcribed spacer Aged AcademicSubjects/MED00260 Crohn's disease biology business.industry Remission Induction C100 Gastroenterology Original Articles C500 General Medicine Middle Aged A300 medicine.disease biology.organism_classification Eccojc/1000 digestive system diseases Gastrointestinal Microbiome Eccojc/1100 Mycoses Case-Control Studies Mutation Immunology Female business |
| Zdroj: | Journal of Crohn's & Colitis JOURNAL OF CROHNS & COLITIS |
| ISSN: | 1876-4479 1873-9946 |
| DOI: | 10.1093/ecco-jcc/jjaa220 |
| Popis: | Background and Aims Historical and emerging data implicate fungi in Crohn’s disease [CD] pathogenesis. However, a causal link between mycobiota, dysregulated immunity, and any impact of NOD2 variants remains elusive. This study aims to evaluate associations between NOD2 variants and faecal mycobiota in CD patients and non-CD subjects. Methods Faecal samples were obtained from 34 CD patients [18 NOD2 mutant, 16 NOD2 wild-type] identified from the UK IBD Genetics Consortium. To avoid confounding influence of mucosal inflammation, CD patients were in clinical remission and had a faecal calprotectin Results CD was associated with higher numbers of fungal observed taxonomic units [OTUs] [p = 0.033]. Principal coordinates analysis using Jaccard index [p = 0.018] and weighted Bray-Curtis dissimilarities [p = 0.01] showed Candida spp. clustered closer to CD patients whereas Cryptococcus spp. clustered closer to non-CD. In CD, we found higher relative abundance of Ascomycota [p = 0.001] and lower relative abundance Basidiomycota [p = 0.019] phyla. An inverse relationship was found between bacterial and fungal Shannon diversity in NOD2 wild-type which was independent of CD [r = -0.349; p = 0.029]. Conclusions This study confirms compositional changes in the gut mycobiota in CD and provides evidence that fungi may play a role in CD pathogenesis. No NOD2 genotype-specific differences were observed in the faecal mycobiota. |
| Databáze: | OpenAIRE |
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