The bacteria hypothesis of colorectal cancer: pathogenetic and therapeutic implications

It is estimated that up to 20% of malignancies worldwide can be attributed to infections. The most convincing evidence, in this context, is the link between Helicobacter pylori and both gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. A growing body of evidence in the last years has raised up the question of the putative causal role of gut microbiota in the carcinogenetic process. Bacteria are an important component of the human body. The human intestine contains >500 different types of microorganisms, usually referred to as the commensal intestinal microbiota. A chronic alteration of the intestinal microbiota homeostasis or dysbiosis” underlies many diseases, including cancer. The main mechanisms by which bacteria may induce carcinogenesis include chronic inflammation, immune evasion and immune suppression. If the microbiota is involved in cancer development, being the colon the site where the microbiota reaches its highest concentration, it is expected to be its major site of action. Numerous data from experimental, animal model and human studies support the gut-bacteria hypothesis of colorectal cancer (CRC). Germ-free rats, compared with conventionally reared animals, develop fewer and smaller tumors both spontaneously and after chemically-induced CRC. The absence of the physiological inflammation caused by the commensal microbiota may explain the capability of the germ-free rats to develop a more efficacious anti-cancer immune response. Several microorganisms, including Streptococcus bovis, Bacteroides fragilis and Escherichia coli have been implicated in the pathogenesis of CRC. The emerging relationship between gut microbiota and cancer prompts new ways of thinking about cancer prevention and leads to the development of innovative treatments such as probiotics. However, although in vitro and animal model studies suggest a protective anticancer effect of probiotics, the results of human epidemiological studies are still controversial and very few data are available from interventional studies