P173 急性重度溃疡性结肠炎肠道微生物群和结肠免疫反应的特征:多组学 ITAC 项目

P Riviere, M Dallmann-Sauer, R Enaud, T Bessissow, X Treton, M Uzzan, F Poullenot, F Zerbib, D Laharie, E Schurr
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We analyzed gut microbiota using 16S rRNA gene sequencing and conducted single-cell RNA-Seq on rectal biopsies in a subgroup of patients to uncover cellular subtypes and pathways involved in mucosal inflammation. We utilized whole blood RNA-Seq to investigate the host pathways involved in mediating systemic inflammation. Results Forty-one patients (23 (56%) female, median (interquartile range IQR) age 42 (34 – 57) years were included: 19 with acute severe UC and 22 with non-severe UC. Compared to patients with non-severe UC, those with acute severe UC displayed distinct gut microbiota with reduced diversity, increased Proteobacteria (Escherichia/Shigella genus), and decreased Lachnospiraceae and Ruminococcaceae. 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引用次数: 0

摘要

背景 对急性重度溃疡性结肠炎(UC)发病机制的了解有限。由于微生物与感染性结肠炎的相似性以及肠道微生物群在 UC 相关炎症中的重要作用,微生物被认为是潜在的诱发因素。我们的目的是确定与急性重症 UC 相关的微生物组要素和宿主因素。方法 这是一项前瞻性研究,比较了三个转诊中心的两组 UC 患者:急性重症住院 UC(根据 Truelove 和 Witts 标准)和非重症 UC。我们使用 16S rRNA 基因测序分析了肠道微生物群,并对亚组患者的直肠活检组织进行了单细胞 RNA-Seq 分析,以揭示参与粘膜炎症的细胞亚型和通路。我们利用全血 RNA-Seq 研究了参与介导全身炎症的宿主通路。结果 共纳入 41 名患者(23(56%)名女性,中位数(四分位数间距 IQR)年龄 42(34 - 57)岁):其中 19 人患有急性重症 UC,22 人患有非重症 UC。与非重度 UC 患者相比,急性重度 UC 患者表现出独特的肠道微生物群,其多样性降低,变形杆菌(埃希氏菌/志贺氏菌属)增加,拉赫诺斯皮拉菌科(Lachnospiraceae)和反刍球菌科(Ruminococcaceae)减少。与非重症病例(n=5 - 18,433 cells)相比,重症病例(n=4 - 13,047 cells)直肠活检的单细胞 RNA-Seq 分析显示出独特的模式:浆细胞显示出改变的转录组特征,IgG 表达增加,白细胞介素 (IL) 26 表达的 T 细胞群扩大。先天性免疫细胞表现出亲炎特征,IL1B 基因表达增加。在血液样本中,我们观察到重症和非重症病例的转录组没有明显的差异。结论 我们的多组学研究揭示了急性重症 UC 发病机制中的关键细胞和细菌成分。我们发现蛋白质细菌,尤其是大肠杆菌是急性重症 UC 的潜在致病菌。在结肠水平,我们观察到 IgG/IgA 比值升高,而 T 细胞和先天性免疫细胞均显示出有利于 Th17 的粘膜环境。急性重症 UC 全身炎症的加剧并没有通过免疫循环细胞的特定变化反映出来。这些见解可能会为未来的研究铺平道路,这些研究的重点是微生物组调节、针对浆细胞的干预措施或对急性重症 UC 中 Th17/IL-23 轴的细微抑制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
P173 Characterization of the gut microbiota and the colonic immune response in acute severe ulcerative colitis : the multi-omics ITAC project
Background Limited understanding exists regarding the pathogenesis of acute severe ulcerative colitis (UC). Microorganisms are proposed as potential triggers due to the resemblances to infectious colitis and the essential role played by gut microbiota in UC-related inflammation. Our aim was to identify microbiome elements and host factors associated with acute severe UC. Methods This was a prospective study across three referral centers comparing two UC patient groups: acute severe hospitalized UC (as per Truelove and Witts criteria) and non-severe UC. We analyzed gut microbiota using 16S rRNA gene sequencing and conducted single-cell RNA-Seq on rectal biopsies in a subgroup of patients to uncover cellular subtypes and pathways involved in mucosal inflammation. We utilized whole blood RNA-Seq to investigate the host pathways involved in mediating systemic inflammation. Results Forty-one patients (23 (56%) female, median (interquartile range IQR) age 42 (34 – 57) years were included: 19 with acute severe UC and 22 with non-severe UC. Compared to patients with non-severe UC, those with acute severe UC displayed distinct gut microbiota with reduced diversity, increased Proteobacteria (Escherichia/Shigella genus), and decreased Lachnospiraceae and Ruminococcaceae. In severe cases (n=4 - 13,047 cells), single-cell RNA-Seq analysis of rectal biopsies revealed distinctive patterns compared to non-severe cases (n=5 - 18,433 cells): plasmablasts showed an altered transcriptomic profile with heightened IgG expression, and there was an expanded cluster of interleukin (IL) 26 expressing T cell population. Innate immune cells exhibited a pro-inflammatory profile marked by increased expression of the IL1B gene. In blood samples, we observed no distinct differentiation of transcriptomic profiles between severe and non-severe cases. Conclusion Our multi-omics study reveals key cellular and bacterial components in acute severe UC pathogenesis. We identified Proteobacteria, especially Escherichia coli as a potential pathobiont in acute severe UC. At the colonic level, we observed an increased IgG/IgA ratio, while both T cells and innate immune cells indicated a pro-Th17 mucosal environment. Enhanced systemic inflammation in acute severe UC was not reflected by specific changes in immune circulating cells. These insights may pave the way for future research focusing on microbiome modulation, interventions targeting plasmablasts, or nuanced inhibition of the Th17/IL-23 axis in acute severe UC.
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