Liu Xiaoyang, Wu Ruihe, Fan Yuxin, Qin Kaili, Li Baochen, Li Xiaofeng, Gao Chong, Wang Caihong
Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Rheumatism Immune Microecology, Taiyuan, Shanxi, China.
Front Immunol. 2025 Jul 25;16:1607804. doi: 10.3389/fimmu.2025.1607804. eCollection 2025.
Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex and diverse etiology. The onset of RA is closely associated with intestinal flora, which is essential for immune regulation.
Fecal samples of 22 healthy controls and 38 patients with newly diagnosed RA were used for performing 16S rRNA sequencing, microbiota diversity assessment, and functional enrichment analysis. Through integrative analysis of random forest feature selection and bidirectional Mendelian randomization (MR), was prioritized as a key bacterial candidate associated with RA. Furthermore, was used to treat the arthritis model mice by gavage treatment, and we evaluated joint inflammation and immune cell profile in mice. Finally, untargeted metabolomics was used to evaluate the changes in serum and fecal metabolites in the arthritis mouse model before and after intervention.
The beta diversity of the intestinal flora exhibited significant differences between RA patients and healthy controls (HC). Functional enrichment analysis revealed that RA patients' intestinal microbiota functions were enriched in pathways like genetic information processing and material metabolism. Further random forest model revealed , etc., and twelve genera with characteristic significance in RA patients. According to further MR analysis, and had a protective effect on RA, and reverse MR analysis showed no evidence of a causal relationship between these groups and RA. experiments showed that after the administration of , the joint inflammation of the mice was relatively slight, the bone destruction and bone density of the joints improved, the proportion of Treg and follicular regulatory T cells (Tfr) cells increased, and the proportion of follicular helper T cells (Tfh) cells decreased. Metabolomic analysis revealed significant changes in both serum and fecal metabolites in mice with collagen-induced arthritis (CIA) compared with healthy controls. The changes in metabolites such as butyric acid were reversed after treatment with .
The study demonstrates that has a protective effect on RA. significantly attenuates joint inflammation in mouse models by may regulating the expression level of butyrate, ameliorating the Treg and Tfr/Tfh immune imbalance status, and re-establishing the immune tolerance. These findings serve as valuable references for future studies on the pathogenesis of RA and the development of new therapeutic approaches.
类风湿关节炎（RA）是一种病因复杂多样的慢性自身免疫性疾病。RA的发病与肠道菌群密切相关，肠道菌群对免疫调节至关重要。
采集22名健康对照者和38例新诊断RA患者的粪便样本，进行16S rRNA测序、微生物群多样性评估和功能富集分析。通过随机森林特征选择和双向孟德尔随机化（MR）的综合分析，将[具体细菌名称1]优先作为与RA相关的关键细菌候选物。此外，通过灌胃治疗用[具体细菌名称1]处理关节炎模型小鼠，并评估小鼠的关节炎症和免疫细胞谱。最后，采用非靶向代谢组学评估关节炎小鼠模型在[具体细菌名称1]干预前后血清和粪便代谢物的变化。
RA患者与健康对照者（HC）的肠道菌群β多样性存在显著差异。功能富集分析显示，RA患者的肠道微生物群功能在遗传信息处理和物质代谢等途径中富集。进一步的随机森林模型显示了[具体细菌名称2]等，以及在RA患者中具有特征意义的12个菌属。根据进一步的MR分析，[具体细菌名称1]和[具体细菌名称2]对RA有保护作用，反向MR分析显示这些菌群与RA之间没有因果关系的证据。[具体细菌名称1]实验表明，给予[具体细菌名称1]后，小鼠的关节炎症相对较轻，关节的骨质破坏和骨密度得到改善，调节性T细胞（Treg）和滤泡调节性T细胞（Tfr）的比例增加，滤泡辅助性T细胞（Tfh）的比例降低。代谢组学分析显示，与健康对照相比，胶原诱导性关节炎（CIA）小鼠的血清和粪便代谢物均有显著变化。用[具体细菌名称1]治疗后，丁酸等代谢物的变化得到逆转。
该研究表明[具体细菌名称1]对RA有保护作用。[具体细菌名称1]可能通过调节丁酸表达水平、改善Treg和Tfr/Tfh免疫失衡状态以及重新建立免疫耐受，显著减轻小鼠模型中的关节炎症。这些发现为未来RA发病机制研究和新治疗方法的开发提供了有价值的参考。
