Fusobacterium nucleatum Prompts Colonic Tumorigenesis in Mice and its Potential Mechanism / 胃肠病学

ABSTRACT

Background:Accumulating evidence links colorectal cancer (CRC) with the gut microbiota.Fusobacterium nucleatum (F.nucleatum) has been revealed to be involved in the development of CRC, however, the mechanism of F.nucleatum in mediating colorectal tumorigenesis is still poorly understood.Aims:To investigate the effect and potential mechanism of F.nucleatum on CRC.Methods:Wild type C57BL/6 mice and APC(Min/+) mice characterized by multiple intestinal neoplasia were used in this animal study.After administered with F.nucleatum intragastrically and/or 1,2-dimethylhydrazine (DMH, a carcinogen) subcutaneously, the aberrant crypt foci (ACF) and colonic tumor were counted at 8th and 20th week, respectively.Structural alteration of intestinal microbiota and mucosal immune factors were detected in wild type C57BL/6 mice receiving different interventions by using Roche 454 GS FLX pyrosequencing and Bio-Plex ProTM cytokine assay, respectively.Results:In DMH-treated wild type C57BL/6 mice or APC(Min/+) mice, number of ACF and colonic tumor in those administered with F.nucleatum were significantly higher than those without (P<0.05).F.nucleatum colonization significantly altered the lumen microbial structure, with decreased Cyanobacterium and increased Tenericutes and Verrucomicrobia (P all <0.05).Furthermore, F.nucleatum up-regulated expressions of tumor-related immune factors in colonic mucosa, such as IL-21, IL-22, IL-31 and CD40L (P<0.05).Conclusions:F.nucleatum colonization in intestine may prompt colonic tumorigenesis in mice via inducing intestinal dysbiosis and modulating tumor-related immune factors expression.