Review Article: The Impact of the Gut Microbiome on Ulcerative Colitis Pharmacotherapy

BACKGROUND: Ulcerative colitis (UC) is a chronic immune-mediated condition of the gastrointestinal tract with highly variable treatment responses. Current therapies focus on suppressing inflammation through aminosalicylates, corticosteroids, immunomodulators, biologics, and small molecules, yet many patients experience suboptimal outcomes, including non-response, partial response, or loss of efficacy over time. This variability has prompted increasing attention to the gut microbiome as a contributing factor. AIMS: This review aimed to compile the current evidence on how the gut microbiome modulates the efficacy and pharmacokinetics of UC therapies, including mechanisms of microbial drug metabolism and host-microbe interactions that affect immune regulation. METHODS: Clinical and preclinical studies exploring the role of the microbiome in UC pharmacotherapy were identified through targeted PubMed and Embase searches. RESULTS: Microbial communities in the gut alter UC drug exposure and action by metabolising active compounds, modifying the host immune response, and influencing local drug absorption and clearance. Differences in microbiome composition and function between individuals may explain some of the heterogeneity in drug response, durability and adverse effect profiles. Clinical studies now show that microbiome characteristics at baseline can correlate with UC treatment outcomes and may even predict therapeutic response. CONCLUSIONS: Understanding these microbiome-drug relationships may improve the precision of UC therapy, support the development of microbiome-guided interventions, and inform future drug development and clinical trial design. Recognising the microbiome as an active variable in treatment response reframes pharmacology in UC as not only drug- and host-dependent but also shaped by the dynamic microbial environment of the gut.