Oncotarget

Research Papers: Pathology:

Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease

Yu-Qun Zeng, Zhenhua Dai, Fuhua Lu, Zhaoyu Lu, Xusheng Liu, Cha Chen, Pinghua Qu, Dingcheng Li, Zhengshuang Hua, Yanni Qu and Chuan Zou _

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Oncotarget. 2016; 7:17468-17478. https://doi.org/10.18632/oncotarget.8160

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Abstract

Yu-Qun Zeng1,*, Zhenhua Dai2,*, Fuhua Lu1, Zhaoyu Lu1, Xusheng Liu1, Cha Chen3, Pinghua Qu3, Dingcheng Li4, Zhengshuang Hua5, Yanni Qu5 and Chuan Zou1

1 Department of Nephrology, The Second Clinical College, Guangzhou University of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, P.R. China

2 Section of Immunology, The Second Clinical College, Guangzhou University of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, P.R. China

3 Department of Laboratory Medicine, The Second Clinical College, Guangzhou University of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, P.R. China

4 Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States of America

5 State Key Laboratory of Biocontrol, Key Laboratory of Biodiversity Dynamics and Conservation of Guangdong Higher Education Institutes, College of Ecology and Evolution, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China

* These authors have contributed equally to this study

Correspondence to:

Chuan Zou, email:

Keywords: emodin, colonic irrigation, gut microbiota, uremic toxins, chronic kidney disease, Pathology Section

Received: November 18, 2015 Accepted: March 01, 2016 Published: March 17, 2016

Abstract

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.


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