Qi Xiang-Yu, Liu Meng-Xia, Jiang Xiao-Jing, Gao Tian, Xu Guo-Qiang, Zhang He-Yi, Su Qin-Yi, Du Yi, Luo Jing, Zhang Sheng-Xiao
Department of Second Clinical Medicine, Shanxi Medical University, Shanxi Province, Taiyuan, China; Shanxi Provincial Key Laboratory of Rheumatism Immune Microecology, Shanxi Province, Taiyuan, China; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Province, Taiyuan, China.
Department of Second Clinical Medicine, Shanxi Medical University, Shanxi Province, Taiyuan, China; Shanxi Provincial Key Laboratory of Rheumatism Immune Microecology, Shanxi Province, Taiyuan, China; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Province, Taiyuan, China; Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Autoimmun Rev. 2025 Aug 16;24(12):103912. doi: 10.1016/j.autrev.2025.103912.
Rheumatoid arthritis (RA) is a systemic autoimmune disease shaped by complex interactions between genetics and environmental factors, among which gut microbiota has emerged as a critical modulator. Recent advances have implicated gut microbiota dysbiosis in RA pathophysiology, with evidence spanning mechanistic, diagnostic, and therapeutic dimensions. This review summarizes current knowledge of the gut-joint axis and outlines microbiota-based strategies for RA management. Numerous studies have demonstrated consistent alterations in gut microbial communities in patients with RA, with enrichment of Prevotella copri observed in 75% of patients with new-onset RA compared to 21.4% of healthy controls, suggesting a potential association with disease initiation. Mechanistically, we detail how microbial dysbiosis, including that of bacteria, fungi, and viruses, disrupts intestinal barrier integrity, skews T helper 17/T regulatory and T follicular helper/T follicular regulatory immune axes, induces molecular mimicry, and alters the profiles of microbial metabolites such as short-chain fatty acids. Diagnostically, microbial taxa and metabolites serve as promising biomarkers. Machine learning models based on microbiota profiles have achieved area under the curve (AUC) values exceeding 0.88, with discriminatory taxa such as Ruminococcus gnavus and Fusicatenibacter. Therapeutically, we reviewed microbiota-targeted interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, diet, and herbal medicines, highlighting the emerging field of pharmacomicrobiomics. Gut microbial signatures have shown promise in predicting treatment responses, including methotrexate efficacy via the enterotype-based gut microbial human index model (AUC = 0.945). This review proposes an integrated framework linking microbial alterations with RA onset and progression and presents gut microbiota as a promising frontier for biomarker discovery, personalized intervention, and precision medicine.
类风湿性关节炎（RA）是一种由遗传和环境因素之间复杂相互作用所塑造的全身性自身免疫性疾病，其中肠道微生物群已成为关键调节因子。最近的进展表明肠道微生物群失调与RA病理生理学有关，证据涵盖机制、诊断和治疗等方面。本综述总结了目前关于肠-关节轴的知识，并概述了基于微生物群的RA管理策略。大量研究表明，RA患者的肠道微生物群落存在一致的改变，75%的新发RA患者中观察到普氏粪杆菌富集，而健康对照中这一比例为21.4%，提示其与疾病起始可能存在关联。从机制上讲，我们详细阐述了微生物失调，包括细菌、真菌和病毒的失调，如何破坏肠道屏障完整性、扭曲辅助性T细胞17/调节性T细胞以及滤泡辅助性T细胞/滤泡调节性T细胞免疫轴、诱导分子模拟，并改变微生物代谢产物如短链脂肪酸的谱。在诊断方面，微生物分类群和代谢产物是很有前景的生物标志物。基于微生物群谱的机器学习模型的曲线下面积（AUC）值超过0.88，具有鉴别意义的分类群如纤细瘤胃球菌和梭形粪杆菌。在治疗方面，我们综述了针对微生物群的干预措施，如益生菌、益生元、抗生素、粪便微生物群移植、饮食和草药，突出了药物微生物组学这一新兴领域。肠道微生物特征在预测治疗反应方面已显示出前景，包括通过基于肠型的肠道微生物人类指数模型预测甲氨蝶呤疗效（AUC = 0.945）。本综述提出了一个将微生物改变与RA发病和进展联系起来的综合框架，并将肠道微生物群作为生物标志物发现、个性化干预和精准医学的一个有前景的前沿领域。
