Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease.
Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease.
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DOI：
10.18632/oncotarget.8160
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发表时间：
2016-04-05
期刊：
影响因子：
--
通讯作者：
Zou C
中科院分区：
文献类型：
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作者：
Zeng YQ;Dai Z;Lu F;Lu Z;Liu X;Chen C;Qu P;Li D;Hua Z;Qu Y;Zou C
肠道微生物群在慢性肾病（CKD）中起着双重作用，并与尿毒症毒素的产生密切相关。通过靶向肠道微生物群来减少尿毒症毒素的策略正在出现。据了解，中药大黄灌肠可以减少尿毒症毒素，改善肾功能。然而，它仍然是未知的成分或机制介导其效果。在这里，我们利用5/6肾切除的大鼠CKD模型来评估大黄的主要成分大黄素对CKD中肠道微生物群和尿毒症毒素的影响。大黄素5 ml（1 mg/d）经结肠灌洗4周。我们发现大黄素通过结肠灌洗（ECI）改变了两种重要的尿毒症毒素，尿素和硫酸吲哚酚（IS）的水平，并改变了CKD大鼠的肠道微生物群。ECI能显著降低尿素和IS，改善肾功能。焦磷酸测序和实时qPCR分析显示，ECI从CKD的异常状态恢复了微生物平衡。10个属与尿素含量呈正相关，4个属与尿素含量呈负相关。此外，3个属与IS呈正相关。因此，大黄素改变了肠道微生物群结构。它减少了有害细菌的数量，如梭菌属。这与尿素和IS都呈正相关，但增加了有益细菌的数量，包括乳杆菌属。与尿素呈负相关。因此，大黄素通过结肠灌洗诱导的肠道微生物群的变化与尿毒症毒素的减少和肾损伤的减轻密切相关。
Gut microbiota plays a dual role in chronic kidney disease (CKD) and is closely linked to production of uremic toxins. Strategies of reducing uremic toxins by targeting gut microbiota are emerging. It is known that Chinese medicine rhubarb enema can reduce uremic toxins and improve renal function. However, it remains unknown which ingredient or mechanism mediates its effect. Here we utilized a rat CKD model of 5/6 nephrectomy to evaluate the effect of emodin, a main ingredient of rhubarb, on gut microbiota and uremic toxins in CKD. Emodin was administered via colonic irrigation at 5ml (1mg/day) for four weeks. We found that emodin via colonic irrigation (ECI) altered levels of two important uremic toxins, urea and indoxyl sulfate (IS), and changed gut microbiota in rats with CKD. ECI remarkably reduced urea and IS and improved renal function. Pyrosequencing and Real-Time qPCR analyses revealed that ECI resumed the microbial balance from an abnormal status in CKD. We also demonstrated that ten genera were positively correlated with Urea while four genera exhibited the negative correlation. Moreover, three genera were positively correlated with IS. Therefore, emodin altered the gut microbiota structure. It reduced the number of harmful bacteria, such as Clostridium spp. that is positively correlated with both urea and IS, but augmented the number of beneficial bacteria, including Lactobacillus spp. that is negatively correlated with urea. Thus, changes in gut microbiota induced by emodin via colonic irrigation are closely associated with reduction in uremic toxins and mitigation of renal injury.