Microbiome-targeted therapies in gastrointestinal diseases: clinical evidence and emerging innovations

Microbiome-targeted therapies are redefining gastroenterology by delivering precision interventions that align with the body’s natural microbial ecosystem. This narrative review evaluates evidence for established approaches, probiotics, prebiotics, fecal microbiota transplantation (FMT), and postbiotics, and examines emerging innovations such as engineered probiotics, bacteriophage therapy, and metabolite-based interventions. Cure rates for recurrent Clostridium difficile infection in randomized trials range from 67% to 94%, depending on route and donor protocol, while multi-strain probiotics provide moderate benefits in inflammatory bowel disease. New modalities, including engineered bacteria and defined bacterial consortia, have progressed to Phase 3 trials, with several granted FDA breakthrough therapy designation. Approvals of Rebyota and Vowst mark a pivotal milestone, creating validated regulatory pathways for microbiome therapeutics. Despite progress, challenges remain in protocol standardisation, patient selection, cost-effectiveness, and clinical integration. Over 200 active trials and growing pharmaceutical investment signal a robust pipeline, with applications expanding to oncology, metabolic disorders, and immune modulation. Continued progress depends on validated biomarkers and personalized strategies guided by microbiome profiling. International regulatory harmonization will also be required to ensure safe and equitable adoption. The field is shifting toward working with, rather than against, the body’s microbial ecosystem, offering substantial potential for personalized gastrointestinal disease management.