Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Ann Med. 2024 Dec;56(1):2338244. doi: 10.1080/07853890.2024.2338244. Epub 2024 Apr 22.
A large proportion of patients with inflammatory bowel disease (IBD) experience IBD-related inflammatory conditions outside of the gastrointestinal tract, termed extraintestinal manifestations (EIMs) which further decreases quality of life and, in extreme cases, can be life threatening. The pathogenesis of EIMs remains unknown, and although gut microbiota alterations are a well-known characteristic of patients with IBD, its relationship with EIMs remains sparsely investigated. This study aimed to compare the gut microbiota of patients with IBD with and without EIMs.
A total of 131 Danish patients with IBD were included in the study, of whom 86 had a history of EIMs (IBD-EIM) and 45 did not (IBD-C). Stool samples underwent 16S rRNA sequencing. Amplicon sequence variants (ASVs) were mapped to the Silva database. Diversity indices and distance matrices were compared between IBD-EIM and IBD-C. Differentially abundant ASVs were identified using a custom multiple model statistical analysis approach, and modules of co-associated bacteria were identified using sparse correlations for compositional data (SparCC) and related to patient EIM status.
Patients with IBD and EIMs exhibited increased disease activity, body mass index, increased fecal calprotectin levels and circulating monocytes and neutrophils. Microbiologically, IBD-EIM exhibited lower fecal microbial diversity than IBD-C (Mann-Whitney's test, = .01) and distinct fecal microbiota composition (permutational multivariate analysis of variance; weighted UniFrac, = 0.018, = .01). A total of 26 ASVs exhibited differential relative abundances between IBD-EIM and IBD-C, including decreased and and increased in the IBD-EIM group. SparCC analysis identified 27 bacterial co-association modules, three of which were negatively related to EIM (logistic regression, < .05) and included important health-associated bacteria, such as and .
The fecal microbiota in IBD patients with EIMs is distinct from that in IBD patients without EIM and could be important for EIM pathogenesis.
很大一部分炎症性肠病（IBD）患者会出现胃肠道以外的 IBD 相关炎症性疾病，称为肠外表现（EIMs），这进一步降低了生活质量，在极端情况下，甚至可能危及生命。EIMs 的发病机制尚不清楚，尽管肠道微生物群的改变是 IBD 患者的一个众所周知的特征，但它与 EIMs 的关系仍鲜有研究。本研究旨在比较有和无 EIM 的 IBD 患者的肠道微生物群。
本研究共纳入 131 名丹麦 IBD 患者，其中 86 名有 EIM 病史（IBD-EIM），45 名没有（IBD-C）。粪便样本进行 16S rRNA 测序。扩增子序列变异（ASVs）被映射到 Silva 数据库。比较 IBD-EIM 和 IBD-C 之间的多样性指数和距离矩阵。使用定制的多模型统计分析方法识别差异丰度 ASVs，并使用稀疏相关的组成数据（SparCC）识别与患者 EIM 状态相关的共关联细菌模块。
患有 IBD 和 EIM 的患者表现出更高的疾病活动度、体重指数、粪便钙卫蛋白水平升高以及循环单核细胞和中性粒细胞增多。微生物学上，IBD-EIM 的粪便微生物多样性低于 IBD-C（Mann-Whitney 检验， = .01），且粪便微生物组成明显不同（置换多元方差分析；加权 UniFrac， = .018， = .01）。共有 26 个 ASVs 在 IBD-EIM 和 IBD-C 之间表现出差异相对丰度，包括 IBD-EIM 组中 和 的减少和 的增加。SparCC 分析鉴定出 27 个细菌共关联模块，其中 3 个与 EIM 呈负相关（逻辑回归， < .05），并包括重要的与健康相关的细菌，如 和 。
患有 EIM 的 IBD 患者的粪便微生物群与无 EIM 的 IBD 患者不同，这可能对 EIM 的发病机制很重要。
