Journal of King Saud University-Science ( IF 3.7 ) Pub Date : 2021-07-18 , DOI: 10.1016/j.jksus.2021.101545 Zhexin Fan 1, 2 , Bo Yang 1, 2, 3 , R. Paul Ross 3, 4 , Catherine Stanton 3, 5 , Feng Zhang 6 , Jian Sun 6 , Jianxin Zhao 1, 2, 7 , Hao Zhang 1, 2, 7, 8 , Wei Chen 1, 2, 7
Objective
Gut toxicity of methotrexate restricts its long-term clinical application in patients with rheumatoid arthritis (RA). However, the disturbed gut microbiota especially beneficial bacteria induced by methotrexate remain unclear, and the way to alleviate the disturbances is limited. The aim of present study was to elucidate the effects of methotrexate on gut microbiota in RA patients and collagen-induced-arthritis (CIA) rats, and to explore a way targeted for restoring gut microbiota.
Methods
The gut microbiota including lactobacilli and bifidobacterial communities were analyzed by high-throughput sequencing of samples from RA patients and healthy controls (HCs), furthermore, propionate and butyrate were administrated to CIA rats to confirm the effects on gut microbiota.
Results
The findings showed gut microbiota significantly altered, and bifidobacterial community was tolerant to methotrexate while lactobacilli community such as L. delbrueckii, L. manihotivorans and L. intestinalis species under-represented in RA samples. Propionate supplementation was significantly associated with the rebalance of gut microbiota especially lactobacilli species including L. acidophilus, L. intestinalis and L. amylovorus in CIA rats.
Conclusion
Methotrexate disturbed gut microbiota and lactobacilli community in RA patients, and propionate supplementation contributed to normalize lactobacilli community in CIA rats. These findings suggested that propionate may be a potential alleviator for gut microbiota in RA patients treated with methotrexate.
中文翻译:
丙酸盐恢复甲氨蝶呤在类风湿性关节炎中引起的肠道菌群紊乱:从临床到实验
客观的
甲氨蝶呤的肠道毒性限制了其在类风湿性关节炎(RA)患者中的长期临床应用。然而,甲氨蝶呤引起的肠道菌群紊乱,特别是有益菌的紊乱尚不清楚,缓解紊乱的方法有限。本研究的目的是阐明甲氨蝶呤对 RA 患者和胶原诱导性关节炎 (CIA) 大鼠肠道微生物群的影响,并探索一种靶向恢复肠道微生物群的方法。
方法
通过对来自 RA 患者和健康对照 (HC) 的样本进行高通量测序分析了包括乳酸杆菌和双歧杆菌群落在内的肠道微生物群,此外,将丙酸盐和丁酸盐给药于 CIA 大鼠以确认对肠道微生物群的影响。
结果
研究结果显示肠道微生物群显着改变,双歧杆菌群落对甲氨蝶呤耐受,而乳杆菌群落,如德氏乳杆菌、食肉乳杆菌和肠乳杆菌在 RA 样本中代表性不足。丙酸补充剂显著与肠道微生物特别是乳酸杆菌物种,包括再平衡相关的嗜酸乳杆菌,属肠和食淀粉乳杆菌CIA大鼠。
结论
甲氨蝶呤扰乱了 RA 患者的肠道微生物群和乳酸菌群落,补充丙酸盐有助于使 CIA 大鼠的乳酸菌群落正常化。这些发现表明,丙酸盐可能是接受甲氨蝶呤治疗的 RA 患者肠道微生物群的潜在缓解剂。