In 2008, nearly 300,000 Chinese children were hospitalised with kidney disease brought on by supplies of powdered milk deliberately contaminated with melamine to boost the apparent protein content. Although melamine was known to combine with uric acid in the children's bodies to produce harmful kidney stones, the details of the reaction and the role of specific gut microbes were not well understood.
By studying how melamine contributes to the development of kidney stones in rats, the research groups have shown experimentally that gut microbes may be central to understanding melamine-induced kidney failure in humans.
The formation of kidney stones occurs when melamine reacts with cyanuric acid in the kidney to form crystals which cannot be dissolved in the bloodstream. According to the paper, published today in Science Translational Medicine, certain species of gut microbes are responsible for converting melamine into the toxic cyanuric acid, thereby accelerating the rate at which kidney stones are formed.
Tests on rats showed that the presence of microbes of the Klebsiella family tended to facilitate the process of melamine conversion, potentially making them key players in the formation of kidney stones. This study suggests that toxicity in this case is linked to the make-up of gut microbes in the poisoned organism.
"The metabolic activities of gut microbes strongly influence human health in profound ways and have been linked to the development of multiple medical problems ranging from autoimmune diseases, obesity, diabetes, and cardiovascular disease," said Professor Nicholson, head of the Department of Surgery and Cancer at Imperial. "The specific implication of this research is that the expression of the kidney disease in the Chinese contaminated milk scandal is likely to have been mediated by gut bacteria in affected children. The more general implication is that gut microbial status affects the outcome to exposures to environmental and food contaminants."
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Xiaojiao Zheng, Aihua Zhao, Guoxiang Xie, Yi Chi, Linjing Zhao, Houkai Li, Congrong Wang, Yuqian Bao, Weiping Jia, Mike Luther, Mingming Su, Jeremy K. Nicholson* and Wei Jia *Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, UK.
A copy of the published paper: http://stm.sciencemag.org/content/5/172/172ra22.full.
2. About Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges. In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.
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