Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance
Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance
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DOI：
10.1096/fj.201802659rr
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发表时间：
2019-08-01
期刊：
影响因子：
4.8
通讯作者：
Shi, Liyun
中科院分区：
文献类型：
--
作者：
Ji, Jianjian;Ge, Xiaoyin;Shi, Liyun
炎症性肠病（IBD）的特征在于与广泛的肠道生态失调和肠道炎症相关的慢性病理。因此，正在努力通过操纵肠道微生物群来改善炎症病理学。瑞香素（DAPH）是从金边瑞香中提取的一种香豆素衍生物，具有抗炎和免疫调节作用，已广泛用于治疗炎症性疾病。在此，我们表明DAPH通过减少结肠炎症、改善结肠完整性以及在受损肠中重建免疫和代谢稳态来显著减轻实验性结肠炎。我们的分析表明，DAPH改变了肠道微生物群的组成，并改变了葡聚糖硫酸钠治疗小鼠的代谢特征。特别是，这种药物显著提高了产生短链脂肪酸（SCFA）的肠道微生物群的丰度，这与T-reg细胞的发育增强和促炎性T（h）17细胞分化减少有关。更重要的是，DAPH的保护作用被证明可以通过共居或粪便微生物群移植在结肠炎小鼠中传播，进一步证实了产生SCFA的肠道微生物群在DAPH作用中的重要性。因此，我们首次揭示了DAPH在结肠炎小鼠中重置肠道微生物组和重建免疫稳态的潜力，这可能对治疗IBD具有临床意义。吉，J.，Ge，X.，Chen，Y.，Zhu，B.，吴昆，张杰，Shan，J.，Cheng，H.，什湖，加-地瑞香素通过调节微生物群组成和T-reg/T（h）17平衡改善实验性结肠炎
Inflammatory bowel diseases (IBDs) are characterized by chronic pathologies associated with extensive gut dysbiosis and intestinal inflammation. Hence, endeavors to improve the inflammatory pathology by manipulating gut microbiota are ongoing. Daphnetin (DAPH) is a coumarin derivative extracted from Daphne odora var with anti-inflammatory and immune-regulatory properties that has been widely used in treating inflammatory disorders. Herein, we showed that DAPH remarkably alleviated experimental colitis by reducing colonic inflammation, improving colonic integrity, and reestablishing immune and metabolic homeostasis in the inflicted intestines. Our analysis showed that DAPH modified the composition of gut microbiota and altered the metabolic profiles in dextran sulfate sodium-treated mice. In particular, this agent significantly elevated the abundance of short-chain fatty acid (SCFA)-producing gut microbiota, causatively related with the enhanced development of T-reg cells and the reduced proinflammatory T(h)17 cell differentiation. More critically, the protective effect of DAPH was shown to be transmissible among colitic mice through cohousing or fecal microbiota transplantation, further substantiating the importance of SCFA-producing gut microbiota in DAPH action. We thus for the first time reveal the potential of DAPH in resetting the gut microbiome and reestablishing immune homeostasis in colitic mice, which may have clinical implications for treating IBD.-Ji, J., Ge, X., Chen, Y., Zhu, B., Wu, Q., Zhang, J., Shan, J., Cheng, H., Shi, L. Daphnetin ameliorates experimental colitis by modulating microbiota composition and T-reg/T(h)17 balance.