The Impact of Donor Microbiota Functional Characteristics on Fecal Microbiota Transplantation Efficacy in Inflammatory Bowel Disease

Background: Emerging evidence implicating gut microbial dysbiosis in the pathogenesis of inflammatory bowel disease (IBD) has propelled fecal microbiota transplantation (FMT) into clinical exploration as a microbiota-targeted therapeutic intervention. Nevertheless, heterogeneous therapeutic outcomes across randomized controlled trials underscore the imperative to characterize functional determinants within donor microbiota that mediate clinical efficacy.Objective: We examined how the functional traits of different donor microbiota affect the effectiveness of FMT and its therapeutic benefits in IBD by screening healthy donors with various functional microbiota.Method: Fecal DNA samples from 39 IBD patients and 42 healthy donors underwent 16S rRNA gene sequencing. Differential analysis identified donor-enriched bacterial genera, which were prioritized for functional evaluation based on median abundance thresholds. Dextran sulfate sodium (DSS)-induced colitis mice received fecal microbiota transplants from selected donors, with subsequent assessment of disease activity indices and microbial community shifts through longitudinal 16S sequencing.Results: The gut microbiota's composition and species diversity were found to be different in patients with IBD compared to healthy individuals. IBD patients exhibited a higher presence of the Proteobacteria phylum, as well as the genera Escherichia-Shigella, Megamonas, and Klebsiella. linear discriminant analysis effect size (LEfSe) analysis identified 50 genera of bacteria with varying abundance, revealing that 36 potentially beneficial bacteria were more prevalent in healthy donors. Four high-functioning and four low-functioning donors were selected based on median relative abundance. In experiments with mice receiving FMT, those receiving transplants from high-functioning donors showed significantly better outcomes than those from low-functioning donors and those treated with 5-aminosalicylic acid (5-ASA). The gut microbial diversity and distribution in FMT mice from high-functioning donors resembled that of healthy mice. In comparison to IBD mice, those receiving transplants from high-functioning donors had increased levels of Firmicutes and Bacteroidota phyla, while Verrucomicrobiota and Firmicutes were reduced. Additionally, the abundance of genera such as Lactobacillus and Dubosiella increased, and levels of Lachnospiraceae NK4A136 group, Akkermansia, Turicibacter, and Parabacteroides returned to normal. LEfSe analysis of IBD mice compared to a control group revealed 24 differentially abundant genera, with 11 more prevalent in IBD mice and 13 in normal mice. However, the relative abundance of these 24 genera in FMT-treated mice from high-functioning donors was more similar to that of normal mice, indicating higher treatment success rates.Conclusion: FMT ameliorated IBD symptoms in murine models, with therapeutic efficacy contingent upon donor microbiota functionality. Notably, the transplantation of high-functioning, donor-derived microbial consortia resulted in better outcomes compared to standard interventions.