Growing experimental and clinical evidence suggests that a chronic inflammatory response induced by gut microbiome critically contribute to the development of rheumatoid arthritis (RA). Previous studies demonstrated the disturbance of lymphocyte subpopulations in RA patients. The purpose of this study was to explore the characteristics of gut microbiome and the associations between bacterium and lymphocyte subpopulations as well as cytokines in patients with RA. Fecal samples from 205 RA patients and 199 healthy controls (HCs) were collected for bacterial DNA extraction and 16S ribosomal RNA (rRNA) gene sequencing. The levels of peripheral lymphocyte subpopulation such as T, B, CD4⁺T, CD8⁺T, NK, T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs) of these subjects were detected by flow cytometry combined with standard absolute counting beads. The serum levels of cytokines interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17, tumour necrosis factor-α (TNF-α), and interferon-γ (INF-γ) were tested by flow cytometric bead array (CBA). Alpha and beta diversity of gut microbiome were explored by bioinformatics analysis. Spearman rank correlation test was used to explore the relationships between gut microbiome and lymphocyte subsets as well as serum cytokines. The diversity and relative abundance of intestinal microbiota in patients with RA were significantly different from those in HCs. Detailly, the abundant of phylum Proteobacteria in RA patients was more than that in HCs, while Firmicutes was less than in HCs. There was increased relative abundance of genus Clostridium_XlVa as well as genus Blautia, more abundance of Ruminococcus2 in patients with lower levels of T, B, CD4⁺T, and Tregs. In addition, the relative abundances of Pelagibacterium, Oxalobacter, ClostridiumXlVb, and ClostridiumXVIII were correlated with cytokines. Gut microbiome of RA patients was clearly different from that of HCs. Abnormal bacteria communities are associated with the altered levels of lymphocyte subpopulation and cytokines, which might be one of the pathogenesis of RA.

中文翻译：

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类风湿性关节炎患者的肠道微生物群及其与外周淋巴细胞亚群和细胞因子的相关性

越来越多的实验和临床证据表明，由肠道微生物组诱导的慢性炎症反应对类风湿性关节炎 (RA) 的发展起关键作用。以前的研究证明了 RA 患者淋巴细胞亚群的紊乱。本研究的目的是探讨 RA 患者肠道微生物组的特征以及细菌和淋巴细胞亚群以及细胞因子之间的关联。收集了 205 名 RA 患者和 199 名健康对照 (HC) 的粪便样本，用于细菌 DNA 提取和 16S 核糖体 RNA (rRNA) 基因测序。外周淋巴细胞亚群的水平，如 T、B、CD4 ⁺ T、CD8 ⁺这些受试者的 T、NK、T 辅助 1 (Th1)、Th2、Th17 和调节性 T 细胞 (Tregs) 通过结合标准绝对计数珠的流式细胞术检测。血清细胞因子白细胞介素2（IL-2）、IL-4、IL-6、IL-10、IL-17、肿瘤坏死因子-α（TNF- α）和干扰素-γ（INF- γ）的水平通过流式细胞计数珠阵列（CBA）测试。通过生物信息学分析探索了肠道微生物组的 Alpha 和 Beta 多样性。Spearman秩相关检验用于探讨肠道微生物组与淋巴细胞亚群以及血清细胞因子之间的关系。RA 患者肠道菌群的多样性和相对丰度与 HC 患者显着不同。详细地，丰富的门RA 患者的变形菌比 HC 多，而厚壁菌门比 HC 少。有增加属的相对丰度Clostridium_XlVa以及属Blautia，更丰富的Ruminococcus2患者具有较低水平T，B，CD4的⁺ T，和调节性T细胞。此外，Pelagibacterium、Oxalobacter、ClostridiumXlVb和ClostridiumXVIII的相对丰度与细胞因子有关。RA 患者的肠道微生物组与 HC 的肠道微生物组明显不同。异常细菌群落与淋巴细胞亚群和细胞因子水平的改变有关，这可能是 RA 的发病机制之一。