Targeted Therapies for Inflammatory Bowel Disease and Colorectal Cancer: An Increasing Need for Microbiota-Intestine Mutualism

Journal of International Translational Medicine

Jurjus Abdo¹  Hisham Daouk¹  Matar 0Michel¹  Inaya Hajj Hussein²  Tralongo Pietro³  Leone Angelo³  Tomasello Giovanni⁴ 

[1] Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine American University of Beirut, 1107-2020 Beirut, Lebanon;Department of Biomedical Sciences, Oakland University William Beaumont School of Medicine Rochester, MI 48309, USA;Department of Experimental and Clinical Neurosciences, Section of Histology, University of Palermo, 90133 Palermo, Italy;Euro-Meditteranean Institute of Science and Technology, 90139 Palermo, Italy;

关键词: Microbiota;    Inflammatory bowel disease;    Colorectal cancer;    Ulcerative colitis;    Therapy;   

DOI  :  10.11910/2227-6394.2015.03.02.11

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown