Fecal microbiota transplant in the treatment of inflammatory bowel diseases: new perspectives on delivery, mechanism, and clinical positioning

The gut microbiota, a complex and dynamic community of microorganisms, has emerged as a crucial determinant of human health and well-being in recent years. This microbial ecosystem plays a pivotal role in various physiological processes, including nutrient metabolism, immune system regulation, and intestinal homeostasis. Disruptions in the composition and function of the gut microbiota have been implicated in a wide range of diseases, such as Clostridioides difficile infection (CDI) and inflammatory bowel diseases (IBD). The elucidation of the fundamental relationship between human disease and the gut microbiome has positioned fecal microbiota transplantation (FMT) as a transformative strategy in modern clinical practice. However, while FMT is increasingly explored for a diverse range of systemic diseases, its clinical implementation is relatively limited beyond the management of recurrent CDI. This review examines the evolving role of FMT within the therapeutic framework of chronic inflammation, focusing specifically on IBD. We compare the variable clinical outcomes in IBD with the highly successful model of recurrent CDI, highlighting mechanistic and clinical determinants of response in a different disease context. Additionally, we evaluate the progression of delivery strategies, from conventional fecal suspensions to standardized oral capsule formulations, and their implications for efficacy, safety, and scalability. Furthermore, we explore the diversifying clinical scenarios where FMT may be incorporated in the treatment paradigm of IBD, including primary treatment of active inflammation, prevention of relapse, and its place in combination with current immunosuppressive therapies.