Does oral exposure to cadmium and lead mediate susceptibility to colitis? The dark-and-bright sides of heavy metals in gut ecology

Sci Rep. 2016 Jan 11;6:19200. doi: 10.1038/srep19200.


Although the heavy metals cadmium (Cd) and lead (Pb) are known environmental health concerns, their long-term impacts on gut ecology and susceptibility to gastrointestinal autoimmune diseases have not been extensively investigated. We sought to determine whether subchronic oral exposure to Cd or Pb is a risk factor for the development and progression of inflammatory bowel disease (IBD). Mice were exposed to various doses of CdCl2 or PbCl2 in drinking water for 1, 4 or 6 weeks prior to infection with Salmonella, the induction of colitis with dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). In human cell-based models, exposure to Cd and Pb is associated with reduced transepithelial electric resistance and changes in bacteria-induced cytokine responses. Although 1- and 6-week exposures did not have clear effects on the response to Salmonella infectious challenges, 1-week short-term treatments with CdCl2 tended to enhance intestinal inflammation in mice. Unexpectedly, subchronic exposure to Cd and (to a lesser extent) Pb significantly mitigated some of the symptoms of DSS-induced colitis and reduced the severity of TNBS colitis in a dose-dependent manner. The possible adaptive and immunosuppressive mechanisms by which heavy metals might reduce intestinal inflammation are explored and discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cadmium / administration & dosage
  • Cadmium / adverse effects*
  • Colitis / etiology*
  • Colitis / pathology
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Disease Susceptibility*
  • Female
  • Immune System / cytology
  • Immune System / drug effects
  • Immune System / immunology
  • Immunomodulation / drug effects
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Lead / administration & dosage
  • Lead / adverse effects*
  • Metals, Heavy / administration & dosage
  • Metals, Heavy / adverse effects*
  • Mice
  • Salmonella Infections / complications
  • Salmonella Infections / microbiology
  • Salmonella typhimurium
  • Time Factors
  • Trinitrobenzenesulfonic Acid / adverse effects


  • Metals, Heavy
  • Cadmium
  • Lead
  • Trinitrobenzenesulfonic Acid
  • Dextran Sulfate