Bugs and drugs: The interplay between IBD therapeutics, inflammation and the gut microbiome - implications for colonic carcinogenesis

With the rising global prevalence of inflammatory bowel disease (IBD) and improved patient longevity, the burden of colitis-associated colorectal cancer (CAC) is increasing. Patients with IBD have a higher risk of developing colorectal cancer (CRC) compared with the general population and are typically diagnosed at a younger age than those with sporadic CRC. This elevated risk is driven by chronic and recurrent inflammatory injury to the intestinal mucosa, which plays a central mechanistic role in carcinogenesis. In contrast to the adenoma–carcinoma sequence observed in sporadic CRC, CAC arises through a distinct inflammation–dysplasia–carcinoma pathway with persistent inflammation initiating and promoting tumorigenesis. Evidence strongly implicates the gut microbiota as being a risk factor in both IBD and CRC. This review synthesises current evidence on the role of the gut microbiota across IBD, CRC and CAC, with a particular focus on the impact of IBD therapeutics on colitis-associated carcinogenesis and the intersection with gut microbiota changes. We identify critical gaps in mechanistic understanding and emphasise the urgent need for mechanism-driven, personalised strategies to enable meaningful clinical translation.