title: 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.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Breton
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Univ Lille, Inserm, CHRU Lille, Lille Inflammation Research International Center, U995, Lille, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Vignal
authors.affiliation: Univ Lille, Inserm, CHRU Lille, Lille Inflammation Research International Center, U995, Lille, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Body-Malapel
authors.affiliation: Univ. Lille - Center of Biology and Pathology, Toxicology, CHRU of Lille and EA4483, Lille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Garat
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France.
authors.forename: Coline
authors.initials: C
authors.lastname: Plé
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Foligné
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000009:adverse effects*; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D007107:Immune System / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D056747:Immunomodulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007854:Lead / Q000008:administration & dosage / Q000009:adverse effects*; D019216:Metals, Heavy / Q000008:administration & dosage / Q000009:adverse effects*; D051379:Mice; D012480:Salmonella Infections / Q000150:complications / Q000382:microbiology; D012486:Salmonella typhimurium; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects
chemical_list: D019216:Metals, Heavy; D002104:Cadmium; D007854:Lead; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate