Advance Microbiota Transplantation: A Novel Addition-Subtraction Paradigm for Optimising Faecal Microbiota...

Faecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection but yields inconsistent benefits in chronic indications. As a crude whole-microbiota transplant, FMT contains numerous undefined active components, complicating efforts to ensure treatment predictability and stability. Therefore, we propose Advance Microbiota Transplantation (AMT), a comprehensive, phase-based hypothesis that employs an addition-subtraction strategy throughout the pre-, peri- and post-transplant stages. AMT comprises donor and recipient pre-treatment, procedural optimisation and post-transplant adjuvant interventions to mitigate donor variability, ecological resistance, procedural heterogeneity and unstable engraftment. Through a systematic synthesis of current evidence-based FMT research, we explored how the addition-subtraction strategy can be operationalised to shape the AMT concept and define testable, phase-specific levers, thereby providing a foundation for future clinical translation. In parallel, we appraised the reporting quality using the Preferred Reporting Items for Microbiotherapy (PRIM) and identified six persistently under-reported items that limit the interpretability, comparability, and reproducibility of FMT research. This review aims to facilitate the integration of AMT into clinical practice.