A multi-step screening algorithm for fecal microbiota transplantation donors: integrating metagenomic and metabolomic profiling for improved safety and donor quality assessment.

Background: Fecal Microbiota Transplantation (FMT) has emerged as a highly effective treatment for recurrent Methods: In this prospective cross-sectional study we evaluated 178 stool donor candidates using a novel screening algorithm, which combined extended medical history, blood and urine testing, stool metagenomics (16S rRNA gene sequencing) and metabolomics (short-chain fatty acids), and microbiological stool tests to exclude the stool samples with pathogens and ensure their microbial diversity. Results: The FMT donor screening and selection workflow was developed and included four main steps: 1. Potential donors ( Conclusions: This study establishes a data-driven, high-stringency donor selection framework that provides a rational basis for improving FMT safety and donor quality. Our findings advocate for the standardized implementation of advanced screening technologies, particularly SCFA metabolomics, as a critical quality control step in stool banking. While clinical validation of the efficacy-enhancing potential of this protocol requires prospective studies, the strong association between butyrate-producing microbiota and favorable FMT outcomes, combined with our previous clinical observations, supports the utility of our approach.