Contribution of Gut Microbiota to Colonic and Extracolonic Cancer DevelopmentCompare D. · Nardone G.
Department of Clinical and Experimental Medicine, Gastroenterology Unit, Federico II University of Naples, Naples, Italy
It is estimated that 20% of malignancies worldwide can be attributed to infections, i.e. about 1.2 million cases per year. A typical example of the association between bacterial infection and gastrointestinal malignancies is Helicobacter pylori infection with both gastric cancer and mucosa-associated lymphoid tissue lymphoma. Bacteria are an important component of the human body. The human intestine contains >500 different types of microorganisms, the ‘gut microbiota’, that play important functions such as energetic metabolism, proliferation and survival of epithelial cells, and protection against pathogens. Chronic alteration of intestinal microbiota homeostasis, ‘dysbiosis’, could promote many diseases, including cancer. The mechanisms by which bacteria may induce carcinogenesis include chronic inflammation, immune evasion, and immune suppression. There are three effector pathways of T helper (Th) cell differentiation: Th1 responses promoted by procarcinogenic signal transducer and activator of transcription (Stat)1 and Stat4 signaling, Th2 responses promoted by Stat6 signaling, and Th17 responses promoted by Stat3 signaling. Interestingly, Th1 responses, driven by IL-12 and characterized by IFN-γ production, are typically anticarcinogenic, whereas Th17 responses are activated in various cancers. Furthermore, a T regulatory response, driven by IL-10 and TGF-β, counterbalances the proinflammatory effect of Th17 responses. Elevated numbers of T regulatory cells suppress the innate and adaptive immune responses, thereby contributing to tumor progression. The emerging relationship between gut microbiota and cancer has prompted new ways of thinking about cancer prevention and has led to the development of noninvasive diagnostic tests and innovative treatments, such as with probiotics. However, although in vitro and animal model studies suggest a protective anticancer effect of probiotics, the results of human epidemiological studies are controversial.