Advances and challenges in microbiome transplantation

Over the past two decades, the microbiome has emerged as a central modifier of host health, whose manipulation may prevent or treat disease. Fecal microbiome transplantation (FMT) transfers stool from healthy donors to recipients to restore microbial structure and function. It is universally accepted as therapy for recurrent Clostridioides difficile infection (rCDI) and is studied across metabolic, neurological, oncological, and autoimmune disorders. However, challenges remain, including donor selection, possible transmission of infectious or non-communicable risks, and limited understanding of mechanisms driving benefits. This review summarizes FMT designs, mechanisms, indications, and obstacles. It discusses emerging strategies such as the use of microbial consortia and extra-intestinal microbiome transplantation and suggests that a better understanding of FMT functions, limitations, and off-target effects may enable safer, more generalizable modulation of microbiome-regulated diseases. Such a mechanistic understanding may manifest as refined donor screening, standardized protocols, tracked outcomes, and identified microbes and metabolites inducing durable clinical benefits.