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Gut microbiota mediated the therapeutic efficacies and the side effects of prednisone in the treatment of MRL/lpr mice
Arthritis Research & Therapy ( IF 4.4 ) Pub Date : 2021-09-14 , DOI: 10.1186/s13075-021-02620-w
Mingzhu Wang 1 , Zhengyang Zhu 2 , Xiaoying Lin 1 , Haichang Li 1 , Chengping Wen 1 , Jie Bao 1 , Zhixing He 1
Affiliation  

Growing evidences indicate that the alterations in gut microbiota are associated with the efficacy of glucocorticoids (GCs) in the treatment of systemic lupus erythematosus (SLE). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs. Using the MRL/lpr mice, this study firstly addressed the effects of three doses of prednisone on gut microbiota. Then, this study used fecal microbiota transplantation (FMT) to transfer the gut microbiota of prednisone-treated MRL/lpr mice into the blank MRL/lpr mice to reveal whether the gut microbiota regulated by prednisone had similar therapeutic efficiency and side effects as prednisone. The effects of prednisone on gut microbiota were dose-dependent in the treatment of MRL/lpr mice. After transplantation into MRL/lpr mice, prednisone-regulated gut microbiota could alleviate lupus, which might be due to decreasing Ruminococcus and Alistipes and retaining the abundance of Lactobacillus. However, prednisone-regulated gut microbiota did not exhibit side effects as prednisone. The reason might be that the pathogens upregulated by prednisone could not survive in the MRL/lpr mice as exogenous microbiota, such as Parasutterella, Parabacteroides, and Escherichia-Shigella. These data demonstrated that the transplantation of gut microbiota may be an effective method to obtain the therapeutic effects of GCs and avoid the side effects of GCs.

中文翻译:

肠道微生物群介导泼尼松治疗 MRL/lpr 小鼠的疗效和副作用

越来越多的证据表明,肠道微生物群的改变与糖皮质激素 (GC) 治疗系统性红斑狼疮 (SLE) 的疗效有关。然而,没有证据证明肠道微生物群是否直接介导了 GC 的作用。使用 MRL/lpr 小鼠,这项研究首先解决了三种剂量的泼尼松对肠道微生物群的影响。然后,本研究使用粪便微生物群移植(FMT)将泼尼松处理的 MRL/lpr 小鼠的肠道微生物群转移到空白 MRL/lpr 小鼠中,以揭示受泼尼松调节的肠道微生物群是否具有与泼尼松相似的治疗效率和副作用。在 MRL/lpr 小鼠的治疗中,泼尼松对肠道微生物群的影响呈剂量依赖性。移植到 MRL/lpr 小鼠后,泼尼松调节的肠道微生物群可以减轻狼疮,这可能是由于减少了瘤胃球菌和 Alistipes 并保留了乳酸杆菌的丰度。然而,泼尼松调节的肠道微生物群并没有像泼尼松那样表现出副作用。原因可能是被泼尼松上调的病原体不能作为外源微生物群在 MRL/lpr 小鼠中存活,例如 Parasutterella、Parabacteroides 和 Escherichia-Shigella。这些数据表明,肠道微生物群的移植可能是获得GCs治疗效果并避免GCs副作用的有效方法。原因可能是被泼尼松上调的病原体不能作为外源微生物群在 MRL/lpr 小鼠中存活,例如 Parasutterella、Parabacteroides 和 Escherichia-Shigella。这些数据表明,肠道微生物群的移植可能是获得GCs治疗效果并避免GCs副作用的有效方法。原因可能是被泼尼松上调的病原体不能作为外源微生物群在 MRL/lpr 小鼠中存活,例如 Parasutterella、Parabacteroides 和 Escherichia-Shigella。这些数据表明,肠道微生物群的移植可能是获得GCs治疗效果并避免GCs副作用的有效方法。
更新日期:2021-09-14
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