title: Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease.
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.
authors.affiliation: 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.
authors.forename: Yu-Qun
authors.initials: YQ
authors.lastname: Zeng
authors.affiliation: 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.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Dai
authors.affiliation: 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.
authors.forename: Fuhua
authors.initials: F
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Cha
authors.initials: C
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Pinghua
authors.initials: P
authors.lastname: Qu
authors.affiliation: Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States of America.
authors.forename: Dingcheng
authors.initials: D
authors.lastname: Li
authors.affiliation: 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, PR China.
authors.forename: Zhengshuang
authors.initials: Z
authors.lastname: Hua
authors.affiliation: 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, PR China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Qu
authors.affiliation: 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.
authors.forename: Chuan
authors.initials: C
authors.lastname: Zou
mesh_terms: D000818:Animals; D004642:Emodin / Q000008:administration & dosage*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D007200:Indican / Q000097:blood*; D008297:Male; D064307:Microbiota / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology*; D007507:Therapeutic Irrigation / Q000379:methods; D014508:Urea / Q000097:blood*
chemical_list: D014508:Urea; D004642:Emodin; D007200:Indican
keywords: Pathology Section; chronic kidney disease; colonic irrigation; emodin; gut microbiota; uremic toxins