Rigorous donor screening is fundamental for the safe and effective delivery of faecal microbiota transplant (FMT) services, whether in the treatment of Clostridioides difficile infection (CDI) or within microbiome intervention clinical trials. Donor screening is of paramount importance given the potential risk of pathogen transmission – a feared complication. While rare in practice, documented cases of FMT-associated infections have resulted in significant morbidity and even mortality. Despite the importance of screening, evidence-based approaches to developing donor 63 screening protocols are lacking. Inadequate screening for transmissible pathogens may lead to infections in recipients, while overly cautious screening for pathogens with negligible transmission potential could strain healthcare resources and unnecessarily exclude donors – already in limited supply. This review aimed to evaluate the evidence underpinning current FMT donor screening protocols. We began by comparing protocols from major FMT guidelines and manufacturers, highlighting their differences in lists of screened pathogens, laboratory assays, and clinical characteristics used for donor selection. We critically appraised the existing literature on transmission dynamics for pathogens. These findings were incorporated into a Delphi process with an expert panel group to develop a rational and streamlined screening approach. We further emphasised the importance of maintaining transparency with regards to donor recruitment, screening, monitoring, and traceback record keeping. Finally, we explored future directions in
donor screening, including approaches to monitoring emerging pathogens, and the potential for integration of new technologies, such as metagenomic assays, to enhance and refine donor selection.