本研究旨在阐明与结直肠癌 (CRC) 相比的自身免疫性疾病，特别是系统性红斑狼疮 (SLE) 和炎症性肠病 (IBD) 相关的微生物特征，以确定独特的生物标志物和共同的微生物机制，为特定的治疗方案提供信息我们分析了患有六种自身免疫性疾病（系统性红斑狼疮、炎症性肠病、多发性硬化症、重症肌无力、格雷夫斯病和强直性脊柱炎）患者队列的宏基因组数据集，并将这些数据与结直肠癌宏基因组进行对比，以描绘疾病特异性微生物谱。该研究的重点是从物种概况和功能基因中识别预测生物​​标志物，整合蛋白质-蛋白质相互作用分析，以探索关键信号通路中的效应蛋白及其靶标。在自身免疫性疾病中发现了不同的微生物特征，其中 SLE 和 IBD 之间存在显着的重叠，表明具有共同的微生物基础。重要的预测生物标志物强调了这些条件下不同微生物的影响。蛋白质-蛋白质相互作用分析揭示了针对糖皮质激素信号传导、抗原呈递和白细胞介素 12 信号传导途径的相互作用，为可能的常见疾病机制提供了见解。实验验证证实了宿主蛋白糖皮质激素受体 (NR3C1) 与特定肠道细菌衍生蛋白之间的相互作用，这可能对 SLE 和 IBD 等炎症性疾病具有治疗意义。我们的研究结果强调了肠道微生物组在自身免疫性疾病中的关键作用，为共享肠道菌群提供了见解。和独特的微生物特征。该研究强调了微生物生物标志物在了解疾病机制和指导治疗策略方面的潜在重要性，为基于微生物谱的新型治疗方法铺平了道路。NCT02394964.© 作者（或其雇主）2024。 重复使用经 CC BY-NC 许可。禁止商业再利用。请参阅权利和权限。由 BMJ 代表 EULAR 出版。

This study aims to elucidate the microbial signatures associated with autoimmune diseases, particularly systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), compared with colorectal cancer (CRC), to identify unique biomarkers and shared microbial mechanisms that could inform specific treatment protocols.We analysed metagenomic datasets from patient cohorts with six autoimmune conditions-SLE, IBD, multiple sclerosis, myasthenia gravis, Graves' disease and ankylosing spondylitis-contrasting these with CRC metagenomes to delineate disease-specific microbial profiles. The study focused on identifying predictive biomarkers from species profiles and functional genes, integrating protein-protein interaction analyses to explore effector-like proteins and their targets in key signalling pathways.Distinct microbial signatures were identified across autoimmune disorders, with notable overlaps between SLE and IBD, suggesting shared microbial underpinnings. Significant predictive biomarkers highlighted the diverse microbial influences across these conditions. Protein-protein interaction analyses revealed interactions targeting glucocorticoid signalling, antigen presentation and interleukin-12 signalling pathways, offering insights into possible common disease mechanisms. Experimental validation confirmed interactions between the host protein glucocorticoid receptor (NR3C1) and specific gut bacteria-derived proteins, which may have therapeutic implications for inflammatory disorders like SLE and IBD.Our findings underscore the gut microbiome's critical role in autoimmune diseases, offering insights into shared and distinct microbial signatures. The study highlights the potential importance of microbial biomarkers in understanding disease mechanisms and guiding treatment strategies, paving the way for novel therapeutic approaches based on microbial profiles.NCT02394964.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.