Targeted therapies for inflammatory bowel disease and colorectal cancer: An increasing need for microbiota-intestinal mutualism

Abstract

The involvement of intestinal microbiota and dysbiosis in the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC) is a well-established fact to be taken into real consideration when developing tartgeted therapies. This review aimed to depict what advances in our understanding of the role of intestinal flora in the pathogenesis of IBD and CRC is shaping up the therapeutic protocols of their management. It was demonstrated that there is a circadian regulation of colocytes gene expression in response to microbiota. In addition, dysbiosis leading to a decrease in microbiome biodiversity was also described in IBD patients whereby thick layers of adherent mucosa associated bacteria exist both in ulcerative colitis (UC) and Crohn's disease (CD). Probiotics based approaches using lactobacilli and Bibidobacteria improved clinical symptoms of IBD's through the GALT immune modulation. In addition, fecal microbiota transplantation (FMT) has also been used for IBD treatment. It consists of transferring gastrointestinal microbiota from a healthy donor to an IBD patient by duodenal infusion of liquid stool suspension to establish microbial homeostasis. The passage of bacteria in the injured mucosal zone triggers chronic inflammation and eventually CRC development by creating a carcinogenic environment. Actually, high level of Fusobacterium nucleatun and other bacteria are prevalent in CRC patients, thus suggesting a potential role of these organisms in the initiation and progression processes due to the production of genotoxic metabolites causing a direct damage to DNA integrity. Moreover, regular probiotics intake was shown to actively prevent the whole process. In conclusion, the mutualistic relationship between microbiota and colonic mucosa proved useful in depicting some of the dynamics of the initiation and development of IBD and CRC. Therapies oriented towards establishing equilibrium of intestinal microbiota may represent the key strategy to switch off chronic inflammatory processes hitting colonic mucosa, thus preventing the onset of CRC.