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传统草药衍生的萝卜硫素LFS-01通过选择性改变肠道微生物群和促进肠道γδT细胞来逆转小鼠结肠炎。

Traditional Herbal Medicine-Derived Sulforaphene LFS-01 Reverses Colitis in Mice by Selectively Altering the Gut Microbiota and Promoting Intestinal Gamma-Delta T Cells.

作者信息

Li Ming, Gao Jiali, Tang Yan, Liu Meishuo, Wu Sijin, Qu Kunli, Long Xiangyu, Li Huajun, Liu Min, Liu Yinhui, Yuan Jieli, Mao Lei, Liu Yu, Zheng Xiliang, Wang Erkang, Wang Jin, Yang Yongliang

机构信息

Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Center for Molecular Medicine, School of Life Sciences and Biotechnology, Dalian University of Technology, Dalian, China.

出版信息

Front Pharmacol. 2018 Jan 9;8:959. doi: 10.3389/fphar.2017.00959. eCollection 2017.

Abstract

Sulforaphene (LFS-01) is a natural compound derived from traditional herbal medicine. Here, we show that oral administration of LFS-01 is able to dramatically alter the skewed gut microbiota and reverse colitis in model mice associated with an increase of intestinal γδT cells. Through 16S rDNA sequencing, we showed that LFS-01 can selectively suppress enteric pathogens such as and whereas the protective strains including and were significantly expanded after LFS-01 treatment. Interestingly, we demonstrated that LFS-01 administration can significantly promote the IL-17+γδT cells in model mice in response to the expanded . We verified that the intracellular components of can stimulate the growth of IL-17+γδT cells upon preincubation. The increased IL-17A after LFS-01 treatment in turn recovers the disrupted occludin subcellular location and protects the epithelial barrier in the colon of model mice. Remarkably, LFS-01 does not show apparent toxicity to animals and we demonstrated that LFS-01 also exerts strong protective effects in TNBS-induced colitis rats. Therefore, LFS-01 holds great promise for the treatment of inflammatory bowel disease (IBD) and warrants translation for use in clinical trials. Our work provided a new avenue for the treatment of IBD based on the strategy of harnessing intestinal symbiosis.

摘要

萝卜硫素(LFS - 01)是一种源自传统草药的天然化合物。在此,我们表明口服LFS - 01能够显著改变模型小鼠中失衡的肠道微生物群,并逆转与肠道γδT细胞增加相关的结肠炎。通过16S rDNA测序,我们发现LFS - 01可以选择性抑制诸如[具体病原体1]和[具体病原体2]等肠道病原体,而包括[具体有益菌1]和[具体有益菌2]在内的保护性菌株在LFS - 01处理后显著增加。有趣的是,我们证明给予LFS - 01能够显著促进模型小鼠中IL - 17 + γδT细胞对扩增的[具体有益菌]的反应。我们证实,[具体有益菌]的细胞内成分在预孵育后能够刺激IL - 17 + γδT细胞的生长。LFS - 01处理后IL - 17A的增加反过来恢复了模型小鼠结肠中被破坏的闭合蛋白亚细胞定位,并保护了上皮屏障。值得注意的是,LFS - 01对动物未表现出明显毒性,并且我们证明LFS - 01在三硝基苯磺酸(TNBS)诱导的结肠炎大鼠中也发挥了强大的保护作用。因此,LFS - 01在治疗炎症性肠病(IBD)方面具有巨大潜力,值得转化用于临床试验。我们的工作为基于利用肠道共生策略治疗IBD提供了一条新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d442/5767259/3067c356f504/fphar-08-00959-g001.jpg

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