Researchers from Shanghai Jiaotong University and the University of North Carolina at Greenpolo conducted a systematic study on the toxicity of melamine in mammals, the protagonist of poisonous milk powder incidents in recent years, and the results were recently published in Science The sub-magazine of the magazine "Science-Translational Medicine". Professor Wei Jia of the University of North Carolina (Jia Wei Science Blog) and Associate Professor Aihua Zhao of Shanghai Jiaotong University are co-corresponding authors of this paper.
Melamine is an industrial raw material used to manufacture plastics, paints, fertilizers and other chemical products. Due to its high nitrogen content of 66.6%, in recent years the compound has been added to milk by some illegal manufacturers to increase the protein test content of food. In 2007, cats, dogs and other animals were poisoned and killed in the United States. These poisoned animals were once eaten with melamine-added pet food. In the "Poisonous Milk Powder" incident in China in 2008, tens of thousands of babies in various provinces in China suffered from kidney stones and kidney failure after consuming milk powder supplemented with melamine.
Because melamine is considered not to be absorbed in the human body, it is difficult to form stones alone, and its clinical toxicity mechanism has been unknown so far. This research work found for the first time that melamine in Chinese toxic milk powder caused kidney failure in infants and young children in 2008 is closely related to the metabolism of intestinal bacteria. Some intestinal bacteria, especially those of the genus Klebisella, have the activity of metabolizing nitrogen-containing compounds and can metabolize melamine in the intestine, convert it to cyanuric acid and gradually degrade it. Melamine and cyanuric acid are extremely low in toxicity, but they are easy to combine with each other to form crystals. After these two types of substances enter the blood circulation, they combine with uric acid in the renal tubules to form macromolecular complex stones, block the renal tubules, and cause kidney toxicity.
In the previous research, the researchers found that stones were formed in the kidney of the rat model of nephrotoxicity caused by a single compound of melamine, and the metabolites of intestinal bacteria also changed significantly. Therefore, they proposed the hypothesis that the toxicity of melamine is correlated with the metabolism of intestinal bacteria, and found in the experiment that the renal toxicity of melamine decreased significantly when the intestinal bacteria of rats were inhibited by broad-spectrum antibiotics. In vitro experiments further confirmed that melamine can be degraded by intestinal bacteria cultivated in the feces of experimental animals. These intestinal bacteria use melamine as a nitrogen source for biodegradation, and gradually form melamine diamide and trimer through continuous deamination. Cyanamide monoamide, cyanuric acid. The researchers found bacteria of the genus Klebsiella in a wide variety of intestinal bacteria and verified their ability to transform melamine. They colonized the bacteria of the genus Klebsiella in the intestine of rats and found that the toxicity of melamine increased significantly and the number of stones in the kidneys increased. . This shows that intestinal bacteria, especially Klebsiella, can convert melamine to cyanuric acid, which in turn can cause crystallization and have renal toxicity. The researchers finally inferred the dynamic process of melamine forming stones in the kidney through the ratio of melamine, cyanuric acid, uric acid in the kidney, and in vitro recrystallization experiments, that is, melamine and cyanuric acid first combine to form a nucleus, and then form Melamine-cyanuric acid-uric acid co-crystallizes, and stones block the renal tubules leading to kidney poisoning.
There are significant individual differences in people's daily lives to diet, drug metabolic capacity and biological response, and these individual differences in metabolic and toxic reactions may largely come from differences in intestinal microbes. Related research found that less than 1% of infants and young children developed melamine-induced nephrotoxicity and urinary system diseases after consuming melamine-containing milk powder. Such results suggest that this part of infants and young children are poisoned because of their intestinal The higher abundance of bacteria that can metabolize melamine such as Klebsiella.
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