title: Gut microbiota protects against gastrointestinal tumorigenesis caused by epithelial injury.
abstract: Inflammation is a critical player in the development of both colitis-associated and sporadic colon cancers. Several studies suggest that the microbiota contribute to inflammation and tumorigenesis; however, studies to understand the role of the microbiota in colon tumor development in germ-free (GF) mice are limited. We therefore studied the effects of the microbiota on the development of inflammation and tumors in GF and conventionally raised specific pathogen-free (SPF) mice treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). We discovered that GF mice developed significantly more and larger tumors compared with that in SPF mice after AOM and DSS treatment despite the lack of early acute inflammation in response to chemically induced injury by DSS. Although the extent of intestinal epithelial damage and apoptosis was not significantly different in GF and SPF mice, there was a delay in intestinal epithelial repair to DSS-induced injury in GF mice resulting in a late onset of proinflammatory and protumorigenic responses and increased epithelial proliferation and microadenoma formation. Recolonization of GF mice with commensal bacteria or administration of lipopolysaccharide reduced tumorigenesis. Thus, although commensal bacteria are capable of driving chronic inflammation and tumorigenesis, the gut microbiota also have important roles in limiting chemically induced injury and proliferative responses that lead to tumor development.
authors.affiliation: Authors' Affiliations: Division of Hematology and Oncology, Department of Internal Medicine, Department of Pathology, Comprehensive Cancer Center, Unit for Laboratory Animal Medicine, and Department of Microbiology and Immunology, University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhan
authors.forename: Po-Ju
authors.initials: PJ
authors.lastname: Chen
authors.forename: William D
authors.initials: WD
authors.lastname: Sadler
authors.forename: Fuyuan
authors.initials: F
authors.lastname: Wang
authors.forename: Sara
authors.initials: S
authors.lastname: Poe
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Eaton
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D063646:Carcinogenesis; D003092:Colitis / Q000382:microbiology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D041981:Gastrointestinal Tract / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016207:Cytokines