Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Hospital, Jinju, Republic of Korea.
Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea.
Front Immunol. 2024 Jan 4;14:1286387. doi: 10.3389/fimmu.2023.1286387. eCollection 2023.
The intricate connection between gut microbiota and rheumatoid arthritis (RA) pathogenesis has gained prominence, although the specific microbial species contributing to RA development remain largely unknown. Recent studies have sought to comprehensively explore alterations in the human microbiome, focusing on identifying disease-related microbial species through blood analysis. Consequently, this study aimed to identify RA-associated microbial species using a serum microbial array system and to investigate the efficacy and underlying mechanisms of potential microbial species for RA treatment.
Serum immunoglobulin M levels against 384 intestinal microbial species were assessed using a microbial microarray in patients with RA and healthy individuals. We investigated the therapeutic potential of the identified microbial candidate regarding arthritis development, immune responses, gut barrier function, and gut microbiome using a collagen-induced arthritis (CIA) mouse model.
Our findings revealed significant alterations in antibody levels against 36 microbial species in patients with RA compared to healthy individuals. Notably, the antibody levels against () were decreased in patients with RA and exhibited an inverse correlation with RA disease activity. experiments demonstrated that produced acetate and butyrate, while exhibiting anti-inflammatory properties. In CIA mice, administration suppressed arthritis symptoms, reduced the accumulation of inflammatory monocytes in the mesenteric lymph nodes, and downregulated gene expression of pro-inflammatory cytokines in the ileum. Additionally, supplementation restored intestinal barrier integrity and partially resolved gut microbial dysbiosis in CIA mice. The fecal microbiota in -treated mice corresponded to improved intestinal barrier integrity and reduced inflammatory responses.
This study highlights the potential of serum-based detection of anti-microbial antibodies to identify microbial targets at the species level for RA treatment. Moreover, our findings suggest that , identified through the microbial microarray analysis, holds therapeutic potential for RA by restoring intestinal barrier integrity and suppressing the immunologic response associated with RA.
肠道微生物群与类风湿关节炎（RA）发病机制之间的复杂联系已引起关注，尽管导致 RA 发展的确切微生物种类仍知之甚少。最近的研究试图全面探索人类微生物组的变化，重点是通过血液分析来确定与疾病相关的微生物种类。因此，本研究旨在使用血清微生物阵列系统来鉴定与 RA 相关的微生物种类，并研究潜在微生物种类治疗 RA 的疗效和潜在机制。
使用微生物微阵列评估 RA 患者和健康个体血清中针对 384 种肠道微生物的免疫球蛋白 M 水平。我们使用胶原诱导关节炎（CIA）小鼠模型研究了鉴定出的微生物候选物在关节炎发展、免疫反应、肠道屏障功能和肠道微生物组方面的治疗潜力。
我们的研究结果表明，与健康个体相比，RA 患者针对 36 种微生物的抗体水平存在显著变化。值得注意的是，（）的抗体水平在 RA 患者中降低，与 RA 疾病活动呈负相关。实验表明，产生乙酸和丁酸，同时具有抗炎特性。在 CIA 小鼠中，给药抑制关节炎症状，减少肠系膜淋巴结中炎症性单核细胞的积累，并下调回肠中促炎细胞因子的基因表达。此外，补充可恢复 CIA 小鼠的肠道屏障完整性并部分解决肠道微生物失调。用治疗的小鼠的粪便微生物群与改善的肠道屏障完整性和减少炎症反应相对应。
本研究强调了基于血清的抗微生物抗体检测在鉴定 RA 治疗的微生物靶标方面的潜力。此外，我们的研究结果表明，通过微生物微阵列分析鉴定出的，通过恢复肠道屏障完整性和抑制与 RA 相关的免疫反应，具有治疗 RA 的潜力。
