基于肠道菌群与肠肝轴相关性的决明子“清肝”物质基础与作用机制研究

Gut microbiota and liver diseases are inextricably linked, through the interaction of the” Gut-liver Axis”. Adjusting and correcting the imbalance of gut microbiota, to achieve a new balance and achieve the function of strengthening and exorcising evil spirits, may be one of the biological mechanism of TCM treat disease.. Semen Cassiae with the function of clearing away liver-fire to improve eyesight, moistening the intestines to relax the bowels. However, the material foundation and action mechanism of its “clearing away liver-fire to improve eyesight” are still not clear. We put forward the hypothesis that the effective substance of Cassia seed is acting with the participation of gut microbiota. At the same time as "moisturizing the intestines"，it can adjust the balance of gut microbiota and achieve the function of "clearing liver heat" (protecting liver) through the effect of intestinal liver axis. We plan to adopt proteomics, metabolomics and microbial metabolomics systems biology approaches to analyze the common metabolite production of Semen Cassiae and gut microbiota, and make correlation analysis among these system biology approaches. Thus, revealing the material foundation of its therapeutic effects and clearing away liver-fire mechanism of Semen Cassiae mediated by gut microbiota.

肠道菌群与肝脏疾病有着密不可分的联系，通过肠肝轴效应相互影响。调整并纠正失衡的肠道菌群，实现新平衡并达到扶正驱邪的作用，可能是中药治疗疾病的生物学机制之一。. 中药决明子具有“清肝明目，润肠通便”功效，但其“清肝”的物质基础及作用机制不明确，我们认为决明子的药效物质通过肠道菌群发挥作用，在“润肠燥”同时，调整肠道菌群的平衡，通过肠肝轴效应，达到“清肝热”（保肝）作用。我们对肝损伤模型小鼠给予决明子提取物，采用代谢组学及微生物组学等系统生物学方法对共代谢产物进行分析，并将多组学进行关联分析，阐明其发挥药效的物质基础以及肠道菌群介导的“清肝”的清肝作用机制。

按照本课题申请书及任务书中提出的研究假说，建立非酒精性脂肪肝小鼠模型，在确认决明子的保肝作用研究基础上，设计了粪便微生物移植对决明子保肝作用转移和抗生素诱导的肠道菌群紊乱对决明子保肝作用影响的实验，从正反两个角度对肠道菌群介导的决明子保肝作用机制进行研究，找出决明子改变的关键菌群，并对其潜在功能进行预测。结果表明，决明子及其组分可以调节具有特定代谢功能的肠道微生物的丰度和组成，诱导产生有益于非酒精性脂肪肝的代谢物，减少有害的代谢物，减轻模型小鼠内毒素血症和脂质积累，从而减少脂质毒性、细菌易位等因素引起的肠屏障损伤、肝损伤和炎症反应。最终阐明决明子通过肠道菌群发挥“清肝”的作用机制，为决明子治疗肝脏疾病的作用机制提供参考。