Xu Yao, Xie Runxiang, Weng Yuqing, Fang Yewei, Chen Huimin, Tao Shuan, Zhang He, Ye Yawen, Deng Xinyu, Han Axiang, Jiang Qi, Liang Wei
Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, China.
Health Science Center, Ningbo University, Ningbo, 315211, China.
BMC Gastroenterol. 2025 Jul 1;25(1):468. doi: 10.1186/s12876-025-04061-0.
The rising incidence of Crohn's disease (CD) in Asia underscores the need to explore its underlying mechanisms. The interaction between gut microbiota and the host is strongly linked to CD onset and progression, yet the precise mechanisms remain unclear. Previous studies have demonstrated that Ruminococcus gnavus (R. gnavus) is closely associated with the development and progression of CD. Therefore, this study focuses on the inflammatory role of R. gnavus in CD pathogenesis.
We performed comprehensive 16 S rRNA sequencing on fecal samples from active CD patients, inactive CD patients, and healthy controls. Alongside this, we conducted clinical data and correlation analyses. To identify key microbial genera, we developed and validated a random forest classification model. Additionally, we utilized a dextran sulfate sodium (DSS)-induced colitis model in C57BL/6 mice to explore the inflammatory role of R. gnavus (ATCC 29149).
Our analysis revealed significant shifts in gut microbiome composition across different stages of CD compared to healthy controls. Notably, there was a marked decrease in Agathobacter and an increase in R. gnavus in patients with active CD. The random forest classification model, which was based on six specific genera (Agathobacter, Vicinamibacteraceae, Arthrobacter, Eubacterium coprostanoligenes group, Ruminococcus gnavus group, and Prevotella 9), achieved an AUC of 0.912, effectively distinguishing CD patients from healthy controls. In the DSS-induced colitis model, R. gnavus exacerbated inflammation, significantly increasing levels of IL-6 and TNF-α, and significantly decreasing levels of Claudin-1 and MUC2, further underscoring its critical role in CD pathogenesis.
The identified genera demonstrate potential as diagnostic biomarkers for CD, with R. gnavus playing a key role in the disease's pathogenesis by inducing inflammation in colitis models.
亚洲克罗恩病（CD）发病率的上升凸显了探索其潜在机制的必要性。肠道微生物群与宿主之间的相互作用与CD的发生和发展密切相关，但其确切机制仍不清楚。先前的研究表明，纤细瘤胃球菌（R. gnavus）与CD的发生和发展密切相关。因此，本研究聚焦于R. gnavus在CD发病机制中的炎症作用。
我们对活动期CD患者、非活动期CD患者和健康对照的粪便样本进行了全面的16S rRNA测序。与此同时，我们进行了临床数据和相关性分析。为了识别关键微生物属，我们开发并验证了一个随机森林分类模型。此外，我们利用葡聚糖硫酸钠（DSS）诱导的C57BL/6小鼠结肠炎模型来探索R. gnavus（ATCC 29149）的炎症作用。
我们的分析显示，与健康对照相比，CD不同阶段的肠道微生物群组成发生了显著变化。值得注意的是，活动期CD患者中阿加西杆菌明显减少，而R. gnavus增加。基于六个特定属（阿加西杆菌、维西纳米杆菌科、节杆菌、产粪甾醇真杆菌群、R. gnavus群和普雷沃菌9）的随机森林分类模型的AUC为0.912，有效地区分了CD患者和健康对照。在DSS诱导的结肠炎模型中，R. gnavus加剧了炎症，显著提高了IL-6和TNF-α水平，并显著降低了Claudin-1和MUC2水平，进一步强调了其在CD发病机制中的关键作用。
所识别的属显示出作为CD诊断生物标志物的潜力，R. gnavus通过在结肠炎模型中诱导炎症在疾病发病机制中起关键作用。
