Gut microbiota imbalance and colorectal cancer

Abstract

The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies.

Keywords: Colorectal cancer; Cyclomodulin; Dysbiosis; Gut microbiota; Oxidative stress.

Figure 1

Suspected mechanisms by which the gut bacterial microbiota participates in colorectal carcinogenesis. The bacterial microbiota induces colorectal carcinogenesis through several mechanisms. The primary suspected mechanisms are bacteria-derived genotoxin production, microbial-derived metabolism, the modulation of host defenses and inflammation pathways, oxidative stress induction, and anti-oxidative defense regulation. These mechanisms result in various cellular effects and alterations of host defenses that lead to genomic instability and epithelial cell proliferation, which are involved in colorectal carcinogenesis. ROS: Reactive oxygen species; NOS: Nitrogen species.