Contribution of gut microbiota to colonic and extracolonic cancer development.

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.
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