Dunyach-Remy Catherine, Pouget Cassandra, Pers Yves-Marie, Gaujoux-Viala Cécile, Demattei Christophe, Salipante Florian, Grenga Lucia, Armengaud Jean, Lavigne Jean-Philippe, Jorgensen Christian
Bacterial Virulence and Chronic Infections, INSERM U1047, Univ Montpellier, Department of Microbiology and Hospital Hygiene, CHU Nîmes, Nîmes, France.
Department of Rheumatology, Stem cells, Cellular plasticity, Regenerative medicine and Immunotherapies, IRMB, INSERM UMR1183, University of Montpellier & University Hospital of Montpellier, Montpellier, France.
Curr Res Microb Sci. 2025 Feb 24;8:100366. doi: 10.1016/j.crmicr.2025.100366. eCollection 2025.
The objective of this study was to investigate the link between gut microbiota (GM) dysbiosis, gut inflammation, and bacterial translocation (BT) in recently diagnosed rheumatoid arthritis (RA). This case-control, observational study prospectively recruited recently diagnosed (<12 months) RA patients and age-matched healthy controls (HC) from two French hospitals between July 2014 to March 2018. The primary objective was to investigate GM composition in each group using 16S rRNA sequencing and metaproteomics approaches. Three plasmatic BT markers (sCD14, LPS-binding protein, and number of 16S rRNA gene copies) and one intestinal permeability marker (I-FABP) were quantified in blood samples. Twenty-five were included in each group, and 50 stools and blood samples were analyzed. 16S rRNA gene analysis showed an decrease in in RA patients after Body Mass Index and HLA status. Circulating bacterial DNA (number of copies of the 16S rRNA gene) and plasmatic I-FABP were higher in RA patients compared to HCs ( < 0.01), indicating increased BT and intestinal permeability in these patients. Metaproteomics from stool samples highlighted an increased host humoral immune response in RA, with elevated levels of inflammatory proteins (azurocidin, cathepsin G, neutrophil defensing 1). Gut inflammation may contribute to increased intestinal permeability, leading to BT into the systemic circulation and thus chronic inflammation.
本研究的目的是调查新诊断的类风湿性关节炎（RA）患者肠道微生物群（GM）失调、肠道炎症和细菌易位（BT）之间的联系。这项病例对照观察性研究于2014年7月至2018年3月期间，从两家法国医院前瞻性招募了新诊断（<12个月）的RA患者和年龄匹配的健康对照（HC）。主要目的是使用16S rRNA测序和宏蛋白质组学方法研究每组中的GM组成。在血样中对三种血浆BT标志物（可溶性CD14、脂多糖结合蛋白和16S rRNA基因拷贝数）和一种肠道通透性标志物（I-FABP）进行定量。每组纳入25例，共分析50份粪便和血样。16S rRNA基因分析显示，在调整体重指数和HLA状态后，RA患者中该基因减少。与HC相比，RA患者的循环细菌DNA（16S rRNA基因拷贝数）和血浆I-FABP更高（<0.01），表明这些患者的BT和肠道通透性增加。粪便样本的宏蛋白质组学突出显示RA患者宿主体液免疫反应增强，炎症蛋白（天青杀素、组织蛋白酶G、中性粒细胞防御素1）水平升高。肠道炎症可能导致肠道通透性增加，导致BT进入体循环，从而引发慢性炎症。
