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Melamine-Induced Renal Toxicity Is Mediated by the Gut Microbiota

meijin 添加于 2013/2/18 13:31:25  1623次阅读 | 0次推荐 | 1个评论

Melamine poisoning has become widely publicized after a recent occurrence of renal injury in infants and children exposedto melamine-tainted milk in China. This renal damage is believed to result from kidney stones formed from melamine and uricacid or from melamine and its cocrystallizing chemical derivative, cyanuric acid. However, the composition of the stones andthe mechanism by which the stones are formed in the renal tubules are unknown. We report that cyanuric acid can be producedin the gut by microbial transformation of melamine and serves as an integral component of the kidney stones responsible formelamine-induced renal toxicity in rats. Melamine-induced toxicity in rats was attenuated, and melamine excretion decreasedafter antibiotic suppression of gut microbial activity. We further demonstrated that melamine is converted to cyanuric acidin vitro by bacteria cultured from normal rat feces; Klebsiella was subsequently identified in fecal samples by 16S ribosomal DNA sequencing. In culture, Klebsiella terrigena was shown to convert melamine to cyanuric acid directly. Rats colonized by K. terrigena showed exacerbated melamine-induced nephrotoxicity. Cyanuric acid was detected in the kidneys of rats administered melaminealone, and the concentration after Klebsiella colonization was increased. These findings suggest that the observed toxicity of melamine may be conditional on the exactcomposition and metabolic activities of the gut microbiota.

作 者:Xiaojiao Zheng1,2,*, Aihua Zhao1,2,*,†, Guoxiang Xie3, Yi Chi2, Linjing Zhao2, Houkai Li3, Congrong Wang1, Yuqian Bao1, Weiping Jia1, Mike Luther4, Mingming Su4, Jeremy K. Nicholson5 and Wei Jia1,2,3,†
期刊名称: Science Translational Medicine
期卷页: 02/13/2013 第5卷 第172期 172ra22~172ra22页
学科领域:医学科学 » 消化系统 » 药物、毒物及酒精性消化系统疾病
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原文链接:http://stm.sciencemag.org/content/5/172/172ra22
DOI: 10.1126/scitranslmed.3005114
ISBN: 1946-6234
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