title: Antibiotic suppression of intestinal microbiota reduces heme-induced lipoperoxidation associated with colon carcinogenesis in rats.
abstract: Epidemiological studies show that heme iron from red meat is associated with increased colorectal cancer risk. In carcinogen-induced-rats, a heme iron-rich diet increases the number of precancerous lesions and raises associated fecal biomarkers. Heme-induced lipoperoxidation measured by fecal thiobarbituric acid reagents (TBARs) could explain the promotion of colon carcinogenesis by heme. Using a factorial design we studied if microbiota could be involved in heme-induced carcinogenesis, by modulating peroxidation. Rats treated or not with an antibiotic cocktail were given a control or a hemoglobin-diet. Fecal bacteria were counted on agar and TBARs concentration assayed in fecal water. The suppression of microbiota by antibiotics was associated with a reduction of crypt height and proliferation and with a cecum enlargement, which are characteristics of germ-free rats. Rats given hemoglobin diets had increased fecal TBARs, which were suppressed by the antibiotic treatment. A duplicate experiment in rats given dietary hemin yielded similar results. These data show that the intestinal microbiota is involved in enhancement of lipoperoxidation by heme iron. We thus suggest that microbiota could play a role in the heme-induced promotion of colorectal carcinogenesis.
authors.affiliation: a Université de Toulouse , UMR1331 Toxalim INRA, Toulouse , France.
authors.forename: O C B
authors.initials: OC
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.forename: N
authors.initials: N
authors.lastname: Naud
authors.forename: S
authors.initials: S
authors.lastname: Tache
authors.forename: I
authors.initials: I
authors.lastname: Raymond-Letron
authors.forename: D E
authors.initials: DE
authors.lastname: Corpet
authors.forename: F H
authors.initials: FH
authors.lastname: Pierre
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D063646:Carcinogenesis / Q000187:drug effects*; D002432:Cecum / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D015169:Colony Count, Microbial; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D006418:Heme / Q000009:adverse effects / Q000032:analysis / Q000037:antagonists & inhibitors; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D064307:Microbiota / Q000187:drug effects*; D011897:Random Allocation; D011916:Rats, Inbred F344; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D016588:Anticarcinogenic Agents; D015415:Biomarkers; D017392:Thiobarbituric Acid Reactive Substances; D006418:Heme