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首页 » 华人研究 » Sci Transl Med:贾伟等揭示三聚氰胺引发肾衰竭与肠道细菌代谢有关

Sci Transl Med:贾伟等揭示三聚氰胺引发肾衰竭与肠道细菌代谢有关

来源:中国科学报 2013-03-06 00:53

近日,来自上海交大附属第六人民医院转化医学中心主任贾伟带领研究团队,通过发现三聚氰胺引发的婴幼儿肾衰竭与肠道细菌的代谢有着密切关系。相关论文近日在《科学—转化医学》(Science Translational Medicine)上发表,该项研究将进一步加深对于人体肠道细菌在食品安全、药物副作用、环境污染等领域重要性的认识,并对促进个性化治疗有着十分重要的意义。

在“毒奶粉”事件中,因为食用被添加了三聚氰胺的奶粉,中国数万名婴儿出现肾结石,甚至肾功能衰竭。研究人员在实验中发现,三聚氰胺的肾毒性在大鼠肠道细菌通过广谱抗生素抑制时出现显著的下降。体外实验进一步证实,三聚氰胺可以被实验动物的粪便中培养出的肠道细菌所降解,这些肠道菌利用三聚氰胺作为氮源进行生物降解,通过连续脱氨基作用逐步形成三聚氰酸二酰胺、三聚氰酸一酰胺、三聚氰酸。

研究者在种类繁多的肠道细菌中发现Klebsiella属的细菌并验证了其对三聚氰胺的转化能力。他们将Klebsiella属细菌定植于大鼠的肠道中,发现三聚氰胺的毒性显著增加,肾脏中的结石数目增多。由此明确肠道细菌尤其是Klebsiella属能转化三聚氰胺生成三聚氰酸,进而产生结晶而具有肾毒性。

研究者最后通过肾脏中三聚氰胺、三聚氰酸、尿酸的比例以及体外重结晶实验,推断出三聚氰胺在肾脏中形成结石的动态过程,即三聚氰胺和三聚氰酸首先结合形成晶核,继而形成三聚氰胺—三聚氰酸—尿酸的共结晶,结石堵塞肾小管导致肾脏中毒。

该研究还发现,不到1%的婴幼儿在食用含三聚氰胺奶粉后出现三聚氰胺所致的肾毒性和泌尿系统疾病,这样的结果提示这一部分婴幼儿肠道含有较高丰度的能够代谢三聚氰胺的细菌。(生物谷Bioon.com)

Melamine-Induced Renal Toxicity Is Mediated by the Gut Microbiota

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,†

Melamine poisoning has become widely publicized after a recent occurrence of renal injury in infants and children exposed to melamine-tainted milk in China. This renal damage is believed to result from kidney stones formed from melamine and uric acid or from melamine and its cocrystallizing chemical derivative, cyanuric acid. However, the composition of the stones and the mechanism by which the stones are formed in the renal tubules are unknown. We report that cyanuric acid can be produced in the gut by microbial transformation of melamine and serves as an integral component of the kidney stones responsible for melamine-induced renal toxicity in rats. Melamine-induced toxicity in rats was attenuated, and melamine excretion decreased after antibiotic suppression of gut microbial activity. We further demonstrated that melamine is converted to cyanuric acid in 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 melamine alone, and the concentration after Klebsiella colonization was increased. These findings suggest that the observed toxicity of melamine may be conditional on the exact composition and metabolic activities of the gut microbiota.

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