肠道微生物能影响三聚氰胺诱发肾病

北卡罗来纳大学的Wei Jia教授与英国伦敦帝国学院的Jeremy Nicholson教授研究小组合作进行了一项国际研究，研究显示，肠道内的微生物可影响三聚氰胺中毒引起的肾脏疾病的严重程度。

2008年，近30万中国儿童因食用受三聚氰胺（故意添加以提高蛋白质含量）污染的奶粉引发肾脏疾病而住院。虽然已知三聚氰胺与尿酸结合，可在儿童体内产生有害的肾结石，但其细节以及特异性肠道微生物的作用并没有得到很明白。

通过研究三聚氰胺如何引起小鼠肾结石，研究小组的实验结果显示，肠道微生物可能对理解三聚氰胺引起的人肾功能衰竭非常重要。

当三聚氰胺与氰尿酸在肾脏发生反应形成血液中不溶的结晶时，就形成了肾结石。根据最近发表在《科学转化医学》上的一篇文章称，某些种类的肠道菌群在三聚氰胺转化为有毒的氰尿酸过程中发挥作用，从而加速肾结石形成的速度。

小鼠试验表明，克雷伯氏菌家族微生物的存在可促进三聚氰胺的转化，这使他们成为形成肾结石的主要参与者。这项研究表明，在这种情况下，毒性与受损组织的肠道菌群有关。

帝国学院外科与癌症部的负责人，Nicholson 教授说，“肠道微生物的代谢活动在许多方面严重影响了人类健康，与涉及自身免疫性疾病，肥胖，糖尿病和心血管疾病的多种医疗问题有关”。“这项研究的特殊意义在于，中国受污染牛奶丑闻中出现的肾脏疾病可能是受累儿童的肠道细菌所介导。更具普遍的意义是，肠道微生物状态影响环境和食品污染物暴露预后。”

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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