Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China.
Arthritis Res Ther. 2024 Jan 13;26(1):21. doi: 10.1186/s13075-023-03260-y.
Patients with rheumatoid arthritis (RA) showed impaired immune tolerance characterized by reduced follicular regulatory T (Tfr) cells, and they also exhibited altered gut microbiotas and their metabolites in RA. However, the association of gut microbiotas and their metabolites with the immune tolerance mediated by Tfr cells in RA remains unclear.
Peripheral blood and stool samples were collected from 32 new-onset RA patients and 17 healthy controls (HCs) in the Second Hospital of Shanxi Medical University between January 2022 and June 2022. The peripheral blood was used to detect the circulating regulatory T (Treg), helper T(Th)17, Tfr, and follicular helper T (Tfh) cells by modified flow cytometry. The stool samples were used to analyze the gut microbiotas and their metabolites via 16S rDNA sequencing and metabolomic profiling. We aimed to characterize the gut microbiotas and their metabolites in RA and identified their association with Tfr cell-mediated immune tolerance.
The new-onset RA demonstrated reduced Treg and Tfr cells, associated with the disease activity and autoantibodies. There were significant differences in gut microbiotas between the two groups as the results of β diversity analysis (P = 0.039) including 21 differential gut microbiotas from the phylum to genus levels. In which, Ruminococcus 2 was associated with the disease activity and autoantibodies of RA, and it was identified as the potential biomarker of RA [area under curve (AUC) = 0.782, 95% confidence interval (CI) = 0.636-0.929, P = 0.001]. Eleven differential metabolites were identified and participated in four main pathways related to RA. Arachidonic acid might be the potential biomarker of RA (AUC = 0.724, 95% CI = 0.595-0.909, P = 0.038), and it was the core metabolite as the positive association with six gut microbiotas enriched in RA. The reduced Tfr cells were associated with the altered gut microbiotas and their metabolites including the Ruminococcus 2, the arachidonic acid involved in the biosynthesis of unsaturated fatty acid pathway and the 3-methyldioxyindole involved in the tryptophan metabolism pathway.
The breakdown of immune tolerance mediated by reduced Tfr cells was associated with the altered gut microbiotas and their metabolites implying the possible mechanism of RA pathogenesis from the perspective of microecology-metabolism-immune.
类风湿关节炎（RA）患者表现出免疫耐受受损的特征，其滤泡调节性 T（Tfr）细胞减少，同时 RA 患者的肠道微生物群及其代谢物也发生了改变。然而，肠道微生物群及其代谢物与 RA 中 Tfr 细胞介导的免疫耐受之间的关联尚不清楚。
2022 年 1 月至 6 月，在山西医科大学第二医院收集了 32 例新诊断的 RA 患者和 17 例健康对照者（HCs）的外周血和粪便样本。通过改良的流式细胞术检测外周血中的循环调节性 T（Treg）、辅助性 T（Th）17、Tfr 和滤泡辅助性 T（Tfh）细胞。通过 16S rDNA 测序和代谢组学分析粪便样本中的肠道微生物群及其代谢物。我们旨在描述 RA 患者的肠道微生物群及其代谢物，并确定其与 Tfr 细胞介导的免疫耐受之间的关系。
新诊断的 RA 患者的 Treg 和 Tfr 细胞减少，与疾病活动度和自身抗体有关。两组之间的肠道微生物群存在显著差异，这是基于β多样性分析的结果（P=0.039），包括从门到属水平的 21 种差异肠道微生物群。其中，瘤胃球菌 2 与 RA 的疾病活动度和自身抗体有关，被鉴定为 RA 的潜在生物标志物[曲线下面积（AUC）=0.782，95%置信区间（CI）=0.636-0.929，P=0.001]。共鉴定出 11 种差异代谢物，它们参与了与 RA 相关的四条主要途径。花生四烯酸可能是 RA 的潜在生物标志物（AUC=0.724，95%CI=0.595-0.909，P=0.038），它是与 RA 中六种富集的肠道微生物群呈正相关的核心代谢物。减少的 Tfr 细胞与改变的肠道微生物群及其代谢物有关，包括瘤胃球菌 2、参与不饱和脂肪酸生物合成途径的花生四烯酸和参与色氨酸代谢途径的 3-甲氧基二吲哚。
由减少的 Tfr 细胞介导的免疫耐受的破坏与改变的肠道微生物群及其代谢物有关，这暗示了从微生态-代谢-免疫角度研究 RA 发病机制的可能机制。
