Distance burning: how gut microbes promote extraintestinal cancers

Gut microbes play a major role in carcinogenesis of the gastrointestinal tract. We and others have shown in mouse models that colonic bacteria also influence the development of extraintestinal cancers including hepatocellular and mammary carcinomas. Microbes such as Helicobacter hepaticus invoke a proinflammatory microenvironment in the lower bowel that may extend to distant organs, often in the absence of histologically evident inflammation. Innate immunity plays a crucial role in the promotion of liver cancer and other systemic diseases by gut microbes. Additional mechanisms include type 1 adaptive immunity, altered metabolism, and oxidative stress. Emerging links between host genetics, gut microbes, inflammatory bowel disease and colorectal cancer also may prove useful for the correlation of specific bacterial populations with extraintestinal neoplasms. Interruption of deleterious host-microbe networks through judicious use of antibiotics and targeted molecular therapies may help reduce the incidence of liver, breast, and other human cancers.