title: Vancomycin-sensitive bacteria trigger development of colitis-associated colon cancer by attracting neutrophils.
abstract: Inflammatory bowel disease confers an increased risk of developing colitis-associated colon cancer (CAC). During the active colitis or developing tumor stage, commensal bacteria show dynamic translocation. However, whether alteration of the bacterial composition in the gut causes CAC is still unclear. To clarify the effect of commensal bacteria on CAC development, we employed an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced murine CAC model treated with or without antibiotics. In addition, we analyzed the effects of antibiotics on infiltration of myeloid cells, colonic inflammatory responses, and colorectal cancer formation. We found that vancomycin treatment dramatically suppressed tumor development. In addition, AOM/DSS treatment greatly induced the infiltration of Gr-1(high)/CD11b(high) neutrophils to the colon, which led to the production of tumor necrosis factor α and inducible nitric oxide synthase. Vancomycin treatment suppressed the infiltration of neutrophils induced by AOM/DSS. Moreover, vancomycin treatment greatly reduced the colon injury and DNA damage caused by AOM/DSS-induced NO radicals. Our results indicate that vancomycin-sensitive bacteria induced colon inflammation and DNA damage by attracting neutrophils into damaged colon tissue, thus promoting tumor formation.
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.|Department of Food Science and Nutrition, Nagoya Women's University, 3-40 Shioji-cho, Mizuho-ku, Nagoya, Aichi, 467-8610, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Isobe
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000009:adverse effects; D001419:Bacteria / Q000276:immunology*; D003092:Colitis / Q000188:drug therapy* / Q000382:microbiology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D004249:DNA Damage / Q000187:drug effects; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D014640:Vancomycin / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D014640:Vancomycin; D016264:Dextran Sulfate; D001397:Azoxymethane