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CONTEXT Recent evidence suggests that modulation of the gut microbiota may help prevent colorectal cancer. OBJECTIVE The aim of this systematic review was to investigate the role of probiotics and synbiotics in the prevention of colorectal cancer and to clarify potential mechanisms involved. DATA SOURCES The PubMed, ScienceDirect, and LILACS databases were searched for studies conducted in humans or animal models and published up to August 15, 2018. STUDY SELECTION Clinical trials and placebo-controlled experimental studies that evaluated the effects of probiotics and synbiotics in colorectal cancer and cancer associated with inflammatory bowel disease were included. Of 247 articles identified, 31 remained after exclusion criteria were applied. A search of reference lists identified 5 additional studies, for a total of 36 included studies. DATA EXTRACTION Two authors independently assessed risk of bias of included studies and extracted data. Data were pooled by type of study, ie, preclinical or clinical. RESULTS The results showed positive effects of probiotics and synbiotics in preventing colorectal cancer. The main mechanisms identified were alterations in the composition and metabolic activity of the intestinal microbiota; reduction of inflammation; induction of apoptosis and inhibition of tumor growth; modulation of immune responses and cell proliferation; enhanced function of the intestinal barrier; production of compounds with anticarcinogenic activity; and modulation of oxidative stress. CONCLUSIONS Probiotics or synbiotics may help prevent colorectal cancer, but additional studies in humans are required to better inform clinical practice.