Characterization of the fecal microbiome from eight healthy volunteers who qualified as potential FMT donors
Fecal Microbiota Transplantation (FMT) has demonstrated success in treating recurrent Clostridioides difficile infection, but its impact on inflammatory bowel disease (IBD) remains limited. The complexity of donor-recipient interactions, particularly immune responses, has not been fully explored, which may contribute to the inconsistent outcomes observed in IBD. This study introduces a novel approach, Gut Microbiome-Lymphocyte Reaction (GMLR), which evaluates immune responses to donor microbiota in IBD patients to guide optimal donor selection, focusing on cytokines critical to IBD pathophysiology. We observed that the microbiota of eight healthy donors clustered into two distinct microbial groups, with one skewed towards IL17-related downregulation and the other towards IL-22 production. However, despite these distinct clusters, immune responses to FMT were highly individualized across recipients, supporting the high variability of FMT efficacy. To address this issue, we developed an algorithm to calculate a compatibility index, enabling the selection of the most suitable donor for each patient based on their immune response. This tailored approach challenges the "super-donor" model, offering a more precise method to improve FMT outcomes in IBD treatment.
Fecal Microbiota Transplantation (FMT) has demonstrated success in treating recurrent Clostridioides difficile infection, but its impact on inflammatory bowel disease (IBD) remains limited. The complexity of donor-recipient interactions, particularly immune responses, has not been fully explored, which may contribute to the inconsistent outcomes observed in IBD. This study introduces a novel approach, Gut Microbiome-Lymphocyte Reaction (GMLR), which evaluates immune responses to donor microbiota in IBD patients to guide optimal donor selection, focusing on cytokines critical to IBD pathophysiology. We observed that the microbiota of eight healthy donors clustered into two distinct microbial groups, with one skewed towards IL17-related downregulation and the other towards IL-22 production. However, despite these distinct clusters, immune responses to FMT were highly individualized across recipients, supporting the high variability of FMT efficacy. To address this issue, we developed an algorithm to calculate a compatibility index, enabling the selection of the most suitable donor for each patient based on their immune response. This tailored approach challenges the "super-donor" model, offering a more precise method to improve FMT outcomes in IBD treatment.
IRCCS Policlinico Milano