Gut Microbiota and Colorectal Cancer Development: A Closer Look to the Adenoma-Carcinoma Sequence

Abstract

There is wide evidence that CRC could be prevented by regular physical activity, keeping a healthy body weight, and following a healthy and balanced diet. Many sporadic CRCs develop via the traditional adenoma-carcinoma pathway, starting as premalignant lesions represented by conventional, tubular or tubulovillous adenomas. The gut bacteria play a crucial role in regulating the host metabolism and also contribute to preserve intestinal barrier function and an effective immune response against pathogen colonization. The microbiota composition is different among people, and is conditioned by many environmental factors, such as diet, chemical exposure, and the use of antibiotic or other medication. The gut microbiota could be directly involved in the development of colorectal adenomas and the subsequent progression to CRC. Specific gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, and enterotoxigenic Bacteroides fragilis, could be involved in colorectal carcinogenesis. Potential mechanisms of CRC progression may include DNA damage, promotion of chronic inflammation, and release of bioactive carcinogenic metabolites. The aim of this review was to summarize the current knowledge on the role of the gut microbiota in the development of CRC, and discuss major mechanisms of microbiota-related progression of the adenoma-carcinoma sequence.

Keywords: bacteria; colorectal adenoma; colorectal cancer; gut microbiota; polyps.

Figure 1

Dysbiosis and other factors contributing to the adenoma-carcinoma progression. The adenoma-carcinoma progression may occur because of the genomic instability caused by alterations in the gut microbiota. These changes may be supported by diet and lifestyle, which promote dysbiosis, inflammatory state and epithelial DNA damage, thus contributing to CRC development. The carcinogenesis leads to gut niche changes, which may favor the proliferation of opportunistic pathogens.