Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria.
Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology, University of Vienna, Vienna, Austria.
Gastroenterology. 2021 Oct;161(4):1245-1256.e20. doi: 10.1053/j.gastro.2021.06.024. Epub 2021 Jun 17.
BACKGROUND & AIMS: Irritable bowel syndrome (IBS) and inflammatory bowel diseases result in a substantial reduction in quality of life and a considerable socioeconomic impact. In IBS, diagnosis and treatment options are limited, but evidence for involvement of the gut microbiome in disease pathophysiology is emerging. Here we analyzed the prevalence of endoscopically visible mucosal biofilms in gastrointestinal disease and associated changes in microbiome composition and metabolism.
The presence of mucosal biofilms was assessed in 1426 patients at 2 European university-based endoscopy centers. One-hundred and seventeen patients were selected for in-depth molecular and microscopic analysis using 16S ribosomal RNA gene amplicon-sequencing of colonic biopsies and fecal samples, confocal microscopy with deep learning-based image analysis, scanning electron microscopy, metabolomics, and in vitro biofilm formation assays.
Biofilms were present in 57% of patients with IBS and 34% of patients with ulcerative colitis compared with 6% of controls (P < .001). These yellow-green adherent layers of the ileum and right-sided colon were microscopically confirmed to be dense bacterial biofilms. 16S-sequencing links the presence of biofilms to a dysbiotic gut microbiome, including overgrowth of Escherichia coli and Ruminococcus gnavus. R. gnavus isolates cultivated from patient biofilms also formed biofilms in vitro. Metabolomic analysis found an accumulation of bile acids within biofilms that correlated with fecal bile acid excretion, linking this phenotype with a mechanism of diarrhea.
The presence of mucosal biofilms is an endoscopic feature in a subgroup of IBS and ulcerative colitis with disrupted bile acid metabolism and bacterial dysbiosis. They provide novel insight into the pathophysiology of IBS and ulcerative colitis, illustrating that biofilm can be seen as a tipping point in the development of dysbiosis and disease.
肠易激综合征（IBS）和炎症性肠病导致生活质量显著下降，并对社会经济产生重大影响。在 IBS 中，诊断和治疗选择有限，但越来越多的证据表明肠道微生物组参与了疾病的病理生理学。在这里，我们分析了胃肠道疾病中可见的黏膜生物膜的患病率，以及微生物组组成和代谢的相关变化。
在 2 个欧洲大学内镜中心对 1426 名患者进行了黏膜生物膜的存在评估。选择了 117 名患者进行深入的分子和显微镜分析，方法是对结肠活检和粪便样本进行 16S 核糖体 RNA 基因扩增子测序、基于深度学习的图像分析的共聚焦显微镜、扫描电子显微镜、代谢组学和体外生物膜形成测定。
与对照组的 6%相比，IBS 患者中有 57%和溃疡性结肠炎患者中有 34%存在生物膜（P<0.001）。这些黄色绿色的黏附层位于回肠和右半结肠，显微镜下证实为密集的细菌生物膜。16S 测序将生物膜的存在与肠道微生物组的失调联系起来，包括大肠杆菌和鲁米诺氏菌过度生长。从患者生物膜中培养的 R. gnavus 分离株也在体外形成生物膜。代谢组学分析发现生物膜内胆汁酸的积累与粪便胆汁酸排泄相关，将这种表型与腹泻的机制联系起来。
黏膜生物膜的存在是 IBS 和溃疡性结肠炎亚组的内镜特征，伴有胆汁酸代谢紊乱和细菌失调。它们为 IBS 和溃疡性结肠炎的病理生理学提供了新的见解，表明生物膜可以被视为失调和疾病发展的转折点。
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