| Title: | The Impact of NOD2 Genetic Variants on the Gut Mycobiota in Crohn's Disease Patients in Remission and in Individuals Without Gastrointestinal Inflammation |
| Author(s): | Nelson A; Stewart CJ; Kennedy NA; Lodge JK; Tremelling M; Consortium UIG; Probert CS; Parkes M; Mansfield JC; Smith DL; Hold GL; Lees CW; Bridge SH; Lamb CA; |
| Address: | "Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. IBD Pharmacogenetics Group, University of Exeter, Exeter, UK. Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK. Department of Gastroenterology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK. Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Department of Gastroenterology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Gastrointestinal Research Group, University of Aberdeen, Aberdeen, UK. Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia. Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK" |
| ISSN/ISBN: | 1876-4479 (Electronic) 1873-9946 (Print) 1873-9946 (Linking) |
| Abstract: | "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 <250 mug/g; 47 non-CD subjects were included as comparator groups, including 22 matched household [four NOD2 mutant] and 25 non-household subjects with known NOD2 genotype [14 NOD2 mutant] identified by the NIHR BioResource Cambridge. Faecal mycobiota composition was determined using internal transcribed spacer 1 [ITS1] sequencing and was compared with 16S rRNA gene sequences and volatile organic compounds. 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" |
| Keywords: | Adult Aged Case-Control Studies Crohn Disease/*genetics Feces/*microbiology Female Gastrointestinal Microbiome/*genetics Genotype Humans Male Middle Aged Mutation Mycoses/*genetics/*microbiology Nod2 Signaling Adaptor Protein/*genetics Remission Induction; |
| Notes: | "MedlineNelson, Andrew Stewart, Christopher J Kennedy, Nicholas A Lodge, John K Tremelling, Mark Probert, Chris S Parkes, Miles Mansfield, John C Smith, Darren L Hold, Georgina L Lees, Charlie W Bridge, Simon H Lamb, Christopher A eng 097943/WT_/Wellcome Trust/United Kingdom MC_PC_19003/MRC_/Medical Research Council/United Kingdom MR/S034919/1/MRC_/Medical Research Council/United Kingdom MR/M00533X/1/MRC_/Medical Research Council/United Kingdom WT_/Wellcome Trust/United Kingdom England 2020/10/30 J Crohns Colitis. 2021 May 4; 15(5):800-812. doi: 10.1093/ecco-jcc/jjaa220" |
