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Melamine-induced renal toxicity is mediated by the gut microbiota

Xiaojiao Zheng1, Aihua Zhao, Guoxiang Xie

  • 1Center for Translational Medicine, and Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Science Translational Medicine
|February 15, 2013
PubMed

Insights

Gut microbes transform melamine into cyanuric acid, a key component of kidney stones causing melamine poisoning. Suppressing gut bacteria reduced toxicity, indicating microbiota

Area of Science:

  • Toxicology
  • Microbiology
  • Nephrology

Background:

  • Melamine poisoning, particularly renal injury in infants, gained attention due to tainted milk.
  • Kidney stones, potentially from melamine and uric acid or cyanuric acid, are implicated in melamine-induced renal toxicity.
  • The exact composition and formation mechanism of these stones remain unclear.

Purpose of the Study:

  • To investigate the role of gut microbiota in melamine-induced renal toxicity.
  • To determine if gut bacteria convert melamine to cyanuric acid.
  • To elucidate the mechanism of kidney stone formation in melamine poisoning.

Main Methods:

  • Antibiotic treatment to suppress gut microbial activity in rats.
  • In vitro bacterial culture to assess melamine conversion to cyanuric acid.
  • 16S ribosomal DNA sequencing to identify gut bacteria.
  • Colonization of rats with specific bacterial strains (Klebsiella terrigena).
  • Analysis of kidney stone composition and melamine/cyanuric acid levels.

Main Results:

  • Antibiotic suppression of gut microbes attenuated melamine toxicity and increased melamine excretion.
  • Bacteria from rat feces, identified as Klebsiella, converted melamine to cyanuric acid in vitro.
  • Klebsiella terrigena directly converted melamine to cyanuric acid.
  • Rats colonized with K. terrigena exhibited exacerbated melamine-induced nephrotoxicity.
  • Cyanuric acid was detected in rat kidneys, with higher concentrations after Klebsiella colonization.

Conclusions:

  • Gut microbial transformation of melamine to cyanuric acid is a critical factor in melamine-induced renal toxicity.
  • The gut microbiota composition and metabolic activity influence the severity of melamine poisoning.
  • Targeting gut microbial activity may offer a therapeutic strategy for melamine toxicity.

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