Second Clinical College, Anhui University of Chinese Medicine, Hefei, Anhui, China.
School of Sports Health, Shenyang Sport University, Shenyang, Liaoning, China.
Front Immunol. 2024 Oct 16;15:1475529. doi: 10.3389/fimmu.2024.1475529. eCollection 2024.
In patients with rheumatoid arthritis (RA), intestinal flora imbalance and butyrate metabolism disorders precede clinical arthritis and are associated with the pathogenesis of RA. This imbalance can alter the immunology and intestinal permeability of the intestinal mucosa, leading to damage to the intestinal barrier. In this context, bacteria and their metabolites can enter the bloodstream and reach the distant target tissues of the host, resulting in local inflammation and aggravating arthritis. Additionally, arthritis is also exacerbated by bone destruction and immune tolerance due to disturbed differentiation of osteoclasts and adaptive immune cells. Of note, butyrate is a metabolite of intestinal flora, which not only locally inhibits intestinal immunity and targets zonulin and tight junction proteins to alleviate intestinal barrier-mediated arthritis but also inhibits osteoclasts and autoantibodies and balances the immune responses of T and B lymphocytes throughout the body to repress bone erosion and inflammation. Therefore, butyrate is a key intermediate linking intestinal flora to the host. As a result, restoring the butyrate-producing capacity of intestinal flora and using exogenous butyrate are potential therapeutic strategies for RA in the future.
在类风湿关节炎（RA）患者中，肠道菌群失衡和丁酸盐代谢紊乱先于临床关节炎发生，并与 RA 的发病机制相关。这种失衡会改变肠道黏膜的免疫和肠道通透性，导致肠道屏障受损。在这种情况下，细菌及其代谢产物可以进入血液，并到达宿主的远处靶组织，导致局部炎症和关节炎加重。此外，由于破骨细胞和适应性免疫细胞的分化紊乱，关节炎还会因骨破坏和免疫耐受而加重。值得注意的是，丁酸盐是肠道菌群的代谢产物，它不仅可以局部抑制肠道免疫，靶向 zonulin 和紧密连接蛋白，从而缓解肠道屏障介导的关节炎，还可以抑制破骨细胞和自身抗体，并平衡全身 T 和 B 淋巴细胞的免疫反应，抑制骨质侵蚀和炎症。因此，丁酸盐是连接肠道菌群和宿主的关键中间产物。因此，恢复肠道菌群产生丁酸盐的能力并使用外源性丁酸盐是未来治疗 RA 的潜在策略。
