The Impact of NOD2 Genetic Variants on the Gut Mycobiota in Crohn's Disease Patients in Remission and in Individuals Without Gastrointestinal Inflammation.
The Impact of NOD2 Genetic Variants on the Gut Mycobiota in Crohn's Disease Patients in Remission and in Individuals Without Gastrointestinal Inflammation.
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DOI：
10.1093/ecco-jcc/jjaa220
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发表时间：
2021-05-04
期刊：
影响因子：
--
通讯作者：
Lamb CA
中科院分区：
文献类型：
--
作者：
Nelson A;Stewart CJ;Kennedy NA;Lodge JK;Tremelling M;UK IBD Genetics Consortium;Probert CS;Parkes M;Mansfield JC;Smith DL;Hold GL;Lees CW;Bridge SH;Lamb CA
历史和新出现的数据表明真菌与克罗恩病[CD]发病机制有关。然而，真菌菌群、免疫失调和NOD2变异的任何影响之间的因果关系仍然难以捉摸。本研究旨在评估NOD2变异与乳糜泻患者和非乳糜泻患者粪便菌群之间的关系。来自英国IBD遗传学协会鉴定的34例CD患者的粪便样本[18例NOD2突变型，16例NOD2野生型]。为避免黏膜炎症的混杂影响，CD患者临床缓解且粪钙保护蛋白<250 μg/g；47名非cd受试者作为比较组，包括22名匹配的家庭受试者[4个NOD2突变体]和25名由NIHR BioResource Cambridge鉴定的已知NOD2基因型的非家庭受试者[14个NOD2突变体]。采用内转录间隔物1 [ITS1]测序法测定粪便菌群组成，并与16S rRNA基因序列和挥发性有机物进行比较。CD与观察到的真菌分类单位（OTUs）数量较高相关[p = 0.033]。使用Jaccard指数[p = 0.018]和加权Bray - Curtis差异[p = 0.01]的主坐标分析显示，假丝酵母更接近乳糜泻患者，而隐球菌更接近非乳糜泻患者。在CD中，子囊菌门的相对丰度较高[p = 0.001]，担子菌门的相对丰度较低[p = 0.019]。NOD2野生型细菌和真菌Shannon多样性呈反比关系，与CD无关[r = -0.349]；p = 0.029]。本研究证实了乳糜泻患者肠道菌群的组成变化，并为真菌可能在乳糜泻发病机制中发挥作用提供了证据。在粪便菌群中未观察到NOD2基因型特异性差异。
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.
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