Probiotic drug interactions in ulcerative colitis: a microbiota and metabolite perspective

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease that imposes a substantial lifelong burden on patients, particularly as it commonly develops during adolescence or early adulthood. Despite major advances in pharmacological management, including the introduction of biologic agents and small-molecule therapies, considerable interindividual variability in therapeutic response remains a major clinical challenge. Emerging evidence in pharmacomicrobiomics indicates that the gut microbiota contributes to this variability through bidirectional interactions with drugs. These interactions involve direct microbial biotransformation of drugs, modulation of host metabolic pathways and transport systems, and pharmacodynamic effects mediated by microbiota that collectively influence drug efficacy, safety, and therapeutic outcomes. Strategies aimed at restoring microbial homeostasis, including dietary interventions, probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation, have therefore attracted increasing attention as adjunctive approaches in UC. Among these, probiotics are the most extensively investigated, and selected formulations have demonstrated clinical benefit in inducing and maintaining remission of UC. However, while their direct therapeutic effects have been widely reviewed, considerably less attention has been devoted to understanding how probiotics interact with conventional UC therapies and whether they modify treatment efficacy through pharmacokinetic, pharmacodynamic, or microbiota-mediated mechanisms. This review provides an up-to-date overview of probiotic-drug interactions in UC, with particular emphasis on microbiota- and metabolite-mediated mechanisms that may influence therapeutic efficacy and contribute to interindividual variability in treatment response. Finally, we discuss current concepts for the rational use of probiotics as adjuncts to UC pharmacotherapy and highlight key knowledge gaps and future research directions in this rapidly evolving field. A better understanding of these interactions may ultimately support microbiota-informed therapeutic strategies aimed at optimizing treatment outcomes in UC.