ABSTRACT

The knowledge on how gut microbes contribute to the inflammatory bowel disease (IBD) at the onset of disease is still scarce. We compared gut microbiota in newly diagnosed, treatment-naïve adult IBD (Crohn’s disease (CD) and ulcerative colitis (UC)) to irritable bowel syndrome (IBS) patients and healthy group. Mucosal and fecal microbiota of 49 patients (13 UC, 10 CD, and 26 IBS) before treatment initiation, and fecal microbiota of 12 healthy subjects was characterized by 16S rRNA gene sequencing. Mucosa was sampled at six positions, from terminal ileum to rectum. We demonstrate that mucosal microbiota is spatially homogeneous, cannot be differentiated based on the local inflammation status and yet provides bacterial footprints superior to fecal in discriminating disease phenotypes. IBD groups showed decreased bacterial diversity in mucosa at all taxonomic levels compared to IBS. In CD and UC, Dialister was significantly increased, and expansion of Haemophilus and Propionibacterium characterized UC. Compared to healthy individuals, fecal microbiota of IBD and IBS patients had increased abundance of Proteobacteria, Enterobacteriaceae, in particular. Shift toward reduction of Adlercreutzia and butyrate-producing taxa was found in feces of IBD patients. Microbiota alterations detected in newly diagnosed treatment-naïve adult patients indicate that the microbiota changes are set and detectable at the disease onset and likely have a discerning role in IBD pathophysiology. Our results justify further investigation of the taxa discriminating between disease groups, such as H. parainfluenzae, R. gnavus, Turicibacteriaceae, Dialister, and Adlercreutzia as potential biomarkers of the disease.

摘要

关于肠道微生物在疾病发作时如何导致炎症性肠病 (IBD) 的知识仍然很少。我们比较了新诊断、初治成人 IBD（克罗恩病 (CD) 和溃疡性结肠炎 (UC)）与肠易激综合征 (IBS) 患者和健康组的肠道微生物群。通过 16S rRNA 基因测序对 49 名患者（13 名 UC、10 名 CD 和 26 名 IBS）的粘膜和粪便微生物群以及 12 名健康受试者的粪便微生物群进行了表征。从末端回肠到直肠，在六个位置取样粘膜。我们证明粘膜微生物群在空间上是均匀的，不能根据局部炎症状态进行区分，但在区分疾病表型方面提供优于粪便的细菌足迹。与 IBS 相比，IBD 组在所有分类学水平上均显示粘膜细菌多样性降低。在 CD 和 UC 中，Dialister显着增加，嗜血杆菌和丙酸杆菌的扩增以UC 为特征。与健康个体相比，IBD 和 IBS 患者的粪便微生物群中变形杆菌的丰度增加，尤其是肠杆菌科。在 IBD 患者的粪便中发现了Adlercreutzia和产丁酸类群的减少。在新诊断的未接受过治疗的成年患者中检测到的微生物群改变表明，微生物群变化在疾病发作时就已确定并可检测到，并且可能在 IBD 病理生理学中具有重要作用。我们的结果证明进一步研究区分疾病组的分类群是合理的，例如H. parainfluenzae、R. gnavus、Turicibacteriaceae、Dialister和Adlercreutzia作为该疾病的潜在生物标志物。