The Impact of NOD2 Genetic Variants on the Gut Mycobiota in Crohn's Disease Patients in Remission and in Individuals Without Gastrointestinal Inflammation.
NOD2 genotype
Crohn’s disease
gut mycobiota
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
04 05 2021
04 05 2021
Historique:
pubmed:
30
10
2020
medline:
17
11
2021
entrez:
29
10
2020
Statut:
ppublish
Résumé
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. 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 μg/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. 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]. 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.
Sections du résumé
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 μg/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.
Identifiants
pubmed: 33119074
pii: 5942946
doi: 10.1093/ecco-jcc/jjaa220
pmc: PMC8095387
doi:
Substances chimiques
Nod2 Signaling Adaptor Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
800-812Subventions
Organisme : Wellcome Trust
ID : 097943
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19003
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S034919/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M00533X/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.
Références
Microbiome. 2017 Nov 25;5(1):153
pubmed: 29178920
Cell Host Microbe. 2015 Oct 14;18(4):489-500
pubmed: 26468751
Gut. 2017 May;66(5):813-822
pubmed: 28179361
Cell. 2018 Sep 6;174(6):1388-1405.e21
pubmed: 30193112
Mycologia. 2015 Nov-Dec;107(6):1057-73
pubmed: 26354806
Science. 2016 May 27;352(6289):1116-20
pubmed: 27230380
Nature. 2001 May 31;411(6837):599-603
pubmed: 11385576
Nat Commun. 2016 Jun 10;7:11813
pubmed: 27283905
Gut. 2019 Nov;68(11):1953-1960
pubmed: 31300515
PLoS Pathog. 2014 Apr 10;10(4):e1004050
pubmed: 24722226
Cell Host Microbe. 2019 Mar 13;25(3):377-388.e6
pubmed: 30850233
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13780-5
pubmed: 17699621
Gastroenterology. 2004 Aug;127(2):412-21
pubmed: 15300573
Lancet. 2018 Dec 23;390(10114):2769-2778
pubmed: 29050646
Immunity. 2014 Aug 21;41(2):311-24
pubmed: 25088769
Bioinformatics. 2009 Nov 1;25(21):2855-6
pubmed: 19706745
Gut. 2017 Jun;66(6):1039-1048
pubmed: 26843508
Nature. 2012 Nov 1;491(7422):119-24
pubmed: 23128233
Infect Immun. 2005 Dec;73(12):7967-76
pubmed: 16299289
Appl Environ Microbiol. 2009 Dec;75(23):7537-41
pubmed: 19801464
Nature. 2001 May 31;411(6837):603-6
pubmed: 11385577
Lancet. 2016 Jan 9;387(10014):156-67
pubmed: 26490195
Nat Genet. 2011 Oct 09;43(11):1066-73
pubmed: 21983784
mSphere. 2018 Mar 28;3(2):
pubmed: 29600282
mBio. 2016 Sep 20;7(5):
pubmed: 27651359
Am J Gastroenterol. 2010 Feb;105(2):289-97
pubmed: 19861953
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16731-6
pubmed: 18936492
Inflamm Bowel Dis. 2015 Aug;21(8):1948-56
pubmed: 26083617
Nucleic Acids Res. 2019 Jan 8;47(D1):D259-D264
pubmed: 30371820
Gut. 2012 Aug;61(8):1140-5
pubmed: 22387526
Genome Med. 2014 Dec 02;6(12):107
pubmed: 25587358
Sci Rep. 2019 Jun 27;9(1):9328
pubmed: 31249384
Inflamm Bowel Dis. 2011 Jan;17(1):179-84
pubmed: 20839241
Gastroenterology. 2010 Nov;139(5):1630-41, 1641.e1-2
pubmed: 20637199
Inflamm Bowel Dis. 2018 Feb 15;24(3):583-592
pubmed: 29462388
Gastroenterology. 2003 Jul;125(1):47-57
pubmed: 12851870
Gut. 2018 Jan;67(1):108-119
pubmed: 27802154
J Biol Chem. 2003 Mar 14;278(11):8869-72
pubmed: 12527755
Gut. 2019 Dec;68(Suppl 3):s1-s106
pubmed: 31562236
Gastroenterology. 2002 Sep;123(3):679-88
pubmed: 12198692
Nat Rev Immunol. 2014 Jan;14(1):9-23
pubmed: 24336102
Aliment Pharmacol Ther. 2016 Mar;43(5):596-611
pubmed: 26806034
Gut. 2003 Nov;52(11):1591-7
pubmed: 14570728
Gut. 2011 May;60(5):631-7
pubmed: 21209126
Ann Surg. 2005 Nov;242(5):693-700
pubmed: 16244543
BMC Bioinformatics. 2014 Dec 10;15:374
pubmed: 25492550
Nat Med. 2010 Jan;16(1):90-7
pubmed: 19966812
Cell Host Microbe. 2015 Mar 11;17(3):385-391
pubmed: 25732063
Gut. 2003 Apr;52(4):558-62
pubmed: 12631669
Cell Host Microbe. 2014 Mar 12;15(3):382-392
pubmed: 24629344
PLoS One. 2019 Feb 28;14(2):e0213108
pubmed: 30818349