...........................................................................................................................................4 Key-words ........................................................................................................................................4 Resumo............................................................................................................................................5 Palavras-chave ................................................................................................................................5 Background ......................................................................................................................................6 Colorectal cancer – Impact and carcinogenesis .........................................................................6 Overview of the gut microbiome ..................................................................................................8 Methods .........................................................................................................................................10 Microbiota and Colorectal Cancer .................................................................................................11 Tumorigenesis and dysbiosis – Is there an association? .........................................................11 Microbiome role in tumorigenesis promotion ............................................................................15 Bacterial Driver-Passenger Model and Alpha-bug Hypothesis .......................................................... 15 Mechanisms of interaction with the host ...................................................................................18 Role of individual intestinal bacteria ..........................................................................................20 Fusobacterium nucleatum ................................................................................................................. 20 Escherichia coli.................................................................................................................................. 22 Enteroxigenic Bacteroides fragilis...................................................................................................... 24 Biofilms .......................................................................................................................................25 Beneficial roles of bacteria.........................................................................................................26 Clinical Relevance .........................................................................................................................27 Conclusion and future directions ...................................................................................................29 Appendices ....................................................................................................................................31 Table 1 .......................................................................................................................................31 Table 2 .......................................................................................................................................32 References ....................................................................................................................................34 Beyond Microbiota and Colorectal Cancer: A Critical Review 3 Abbreviations List APC – adenomatous polyposis coli BFT – Bacterioides fragilis toxin BMI – body mass index CEC – colon epithelial cells CRC – colorectal cancer FOBT – fecal occult blood test IBD inflammatory bowel disease MIN – multiple intestinal neoplasia WHO – world health organization