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

Abstract

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.

• Authors: Jérôme Breton, Catherine Daniel, Cécile Vignal, Mathilde Body-Malapel, Anne Garat, Coline Plé, Benoît Foligné
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 19200 (Jan 11 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26752005 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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