J Crohns Colitis. 2024 Oct 15;18(10):1713-1725. doi: 10.1093/ecco-jcc/jjae061.

David A Muñiz Pedrogo ¹, Cynthia L Sears ^2 3, Joanna M P Melia ¹

Author information

¹Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

²Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

³Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

The risk of colorectal cancer [CRC] is increased in patients with inflammatory bowel disease [IBD], particularly in extensive ulcerative colitis [UC] and Crohn's colitis. Gut microbiota have been implicated in the pathogenesis of CRC via multiple mechanisms, including the release of reactive oxygen species and genotoxins, and induction of inflammation, as well as activation of the immune response. Gut microbiota can enhance their carcinogenic and proinflammatory properties by organising into biofilms, potentially making them more resistant to the host's immune system and to antibiotics. Colonic biofilms have the capacity to invade colonic tissue and accelerate tumorigenesis in tumour-prone models of mice. In the context of IBD, the prevalence of biofilms has been estimated to be up to 95%. Although the relationship between chronic inflammation and molecular mediators that contribute to IBD-associated CRC is well established, the role of gut microbiota and biofilms in this sequence is not fully understood. Because CRC can still arise in the absence of histological inflammation, there is a growing interest in identifying chemopreventive agents against IBD-associated CRC. Commonly used in the treatment of UC, 5-aminosalicylates have antimicrobial and anticarcinogenic properties that might have a role in the chemoprevention of CRC via the inhibition or modulation of carcinogenic gut microbiota and potentially of biofilm formation. Whether biologics and other IBD-targeted therapies can decrease the progression towards dysplasia and CRC, via mechanisms independent of inflammation, is still unknown. Further research is warranted to identify potential new microbial targets in therapy for chemoprevention of dysplasia and CRC in IBD.