Department of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fujian, China.
First Clinical College, Fujian Medical University, Fuzhou, China.
Int J Rheum Dis. 2020 Apr;23(4):472-479. doi: 10.1111/1756-185X.13802. Epub 2020 Feb 26.
Gut microbiota play an important role in rheumatoid arthritis (RA). Biological therapies targeting tumor necrosis factor-α (TNF-α) have been used for treatment in RA patients. However, whether TNF-α antagonist has some influence on gut microbiota is still unknown. This study aims to investigate the distribution of gut microbiota in collagen-induced arthritis (CIA) mice treated with the TNF-α antagonist etanercept.
Collagen-induced arthritis mice were induced by type II collagen. Cytokine expression was detected by real-time polymerase chain reaction. 16S ribosomal RNA sequencing was performed to characterize the gut microbiota in CIA mice treated with vehicle or etanercept. Sequencing reads were processed by Microbial Ecology software program.
Compared with vehicle-treated mice, we showed that CIA mice treated with etanercept led to attenuation of inflammation and reduced expression of TNF-α, interferon (IFN)-γ, interleukin (IL)-6 and IL-21. Meanwhile, results showed operational taxonomic units, richness estimators and the diversity indices of gut microbiota in etanercept-treated mice were lower than that in vehicle-treated mice. Moreover, bacterial abundance analyses showed that genus Escherichia/Shigella was more abundant in etanercept-treated mice, and Lactobacillus, Clostridium XlVa, Tannerella were less abundant. The altered bacterial genus was correlated with TNF-α, IFN-γ, IL-6, IL-21 and IL-10.
Our results revealed that TNF-α antagonist treatment can reduce the abundance and diversity of gut microbiota in CIA mice. Targeted gut microbiota may be a new therapeutic strategy for the treatment of RA.
肠道微生物群在类风湿关节炎（RA）中发挥重要作用。针对肿瘤坏死因子-α（TNF-α）的生物疗法已用于 RA 患者的治疗。然而，TNF-α 拮抗剂是否对肠道微生物群有一些影响尚不清楚。本研究旨在探讨 TNF-α拮抗剂依那西普治疗胶原诱导性关节炎（CIA）小鼠肠道微生物群的分布。
通过 II 型胶原诱导胶原诱导性关节炎小鼠。通过实时聚合酶链反应检测细胞因子表达。通过 16S 核糖体 RNA 测序来描述用载体或依那西普治疗的 CIA 小鼠的肠道微生物群。测序读数通过微生物生态学软件程序进行处理。
与载体处理的小鼠相比，我们发现依那西普治疗的 CIA 小鼠导致炎症减轻，TNF-α、干扰素（IFN）-γ、白细胞介素（IL）-6 和 IL-21 的表达减少。同时，结果表明依那西普治疗的小鼠的操作分类单元、丰富度估计值和肠道微生物群的多样性指数低于载体处理的小鼠。此外，细菌丰度分析表明，依那西普治疗的小鼠中埃希氏菌/志贺氏菌属更为丰富，而乳杆菌属、梭状芽胞杆菌 XlVa 属和 Tannerella 属则较少。改变的细菌属与 TNF-α、IFN-γ、IL-6、IL-21 和 IL-10 相关。
我们的结果表明，TNF-α 拮抗剂治疗可降低 CIA 小鼠肠道微生物群的丰度和多样性。靶向肠道微生物群可能是治疗 RA 的一种新的治疗策略。
