Intestinal Dysbiosis: Microbial Imbalance Impacts on Colorectal Cancer Initiation, Progression and Disease Mitigation

Abstract

The human gastrointestinal tract houses a diverse range of microbial species that play an integral part in many biological functions. Several preclinical studies using germ-free mice models have demonstrated that the gut microbiome profoundly influences carcinogenesis and progression. Colorectal cancer appears to be associated with microbial dysbiosis involving certain bacterial species, including F. nucleatum, pks+ E. coli, and B. fragilis, with virome commensals also disrupted in patients. A dysbiosis toward these pro-carcinogenic species increases significantly in CRC patients, with reduced numbers of the preventative species Clostridium butyicum, Roseburia, and Bifidobacterium evident. There is also a correlation between Clostridium infection and CRC. F. nucleatum, in particular, is strongly associated with CRC where it is associated with therapeutic resistance and poor outcomes in patients. The carcinogenic mode of action of pathogenic bacteria in CRC is a result of genotoxicity, epigenetic alterations, ROS generation, and pro-inflammatory activity. The aim of this review is to discuss the microbial species and their impact on colorectal cancer in terms of disease initiation, progression, and metastasis. The potential of anticancer peptides as anticancer agents or adjuvants is also discussed, as novel treatment options are required to combat the high levels of resistance to current pharmaceutical options.