biostudies-literatureUnknown16Dai Z<h4>Background</h4>Growing evidence links gut microbial dysbiosis to inflammatory bowel disease (IBD) pathogenesis, establishing fecal microbiota transplantation (FMT) as a microbiota-targeted therapy; however, variable outcomes in randomized trials highlight the need to identify compositional features of donor microbiota associated with FMT efficacy.<h4>Objective</h4>This study aimed to investigate how the composition of the donor gut microbiota influences the therapeutic efficacy of FMT in IBD.<h4>Method</h4>Fecal DNA from 39 IBD patients and 42 healthy donors was analyzed via 16S rRNA sequencing. Donor-enriched genera (identified through differential analysis and median abundance thresholds) guided FMT selection. Dextran sulfate sodium (DSS)-induced colitis mice received donor microbiota transplants; disease activity and microbiota dynamics were evaluated through longitudinal sequencing.<h4>Results</h4>IBD patients showed reduced microbial diversity and increased Proteobacteria phylum versus healthy donors, as well as the genera <i>Escherichia-Shigella</i>, <i>Megamonas</i>, and <i>Klebsiella</i>. Linear discriminant analysis effect size (LEfSe) analysis identified 50 differentially abundant genera, with 36 beneficial taxa enriched in donors. Based on median abundance of these health-associated genera, four high- and low-abundance donors were selected. FMT from high-abundance donors outperformed low-abundance donors and 5-ASA in colitis mice, restoring microbial diversity to healthy levels. Recipient mice showed increased Firmicutes and Bacteroidota and decreased Verrucomicrobiota, with <i>Lactobacillus</i> and <i>Dubosiella</i> enrichment and normalization of <i>Lachnospiraceae NK4A136 group</i>, <i>Akkermansia</i>, <i>Turicibacter</i>, and <i>Parabacteroides</i>. LEfSe identified 24 genera distinguishing IBD and control mice; post-FMT microbiota of high-abundance donor recipients more closely resembled controls, correlating with therapeutic success.<h4>Conclusion</h4>FMT ameliorated IBD symptoms in murine models, with therapeutic efficacy associated with the relative abundance of health-associated microbial genera in donor microbiota.Frontiers in immunology1635244https://www.ebi.ac.uk/biostudies/studies/S-EPMC12353733biostudies-literatureMicrobiota composition-based donor selection affects FMT efficacy in a murine colitis model.PMC12353733Li GLv YCai JCheng WSun XZhong ZDai ZWang JPeng HLiu XQiu XChen SSun JfalseMicrobiota composition-based donor selection affects FMT efficacy in a murine colitis model.<h4>Background</h4>Growing evidence links gut microbial dysbiosis to inflammatory bowel disease (IBD) pathogenesis, establishing fecal microbiota transplantation (FMT) as a microbiota-targeted therapy; however, variable outcomes in randomized trials highlight the need to identify compositional features of donor microbiota associated with FMT efficacy.<h4>Objective</h4>This study aimed to investigate how the composition of the donor gut microbiota influences the therapeutic efficacy of FMT in IBD.<h4>Method</h4>Fecal DNA from 39 IBD patients and 42 healthy donors was analyzed via 16S rRNA sequencing. Donor-enriched genera (identified through differential analysis and median abundance thresholds) guided FMT selection. Dextran sulfate sodium (DSS)-induced colitis mice received donor microbiota transplants; disease activity and microbiota dynamics were evaluated through longitudinal sequencing.<h4>Results</h4>IBD patients showed reduced microbial diversity and increased Proteobacteria phylum versus healthy donors, as well as the genera <i>Escherichia-Shigella</i>, <i>Megamonas</i>, and <i>Klebsiella</i>. Linear discriminant analysis effect size (LEfSe) analysis identified 50 differentially abundant genera, with 36 beneficial taxa enriched in donors. Based on median abundance of these health-associated genera, four high- and low-abundance donors were selected. FMT from high-abundance donors outperformed low-abundance donors and 5-ASA in colitis mice, restoring microbial diversity to healthy levels. Recipient mice showed increased Firmicutes and Bacteroidota and decreased Verrucomicrobiota, with <i>Lactobacillus</i> and <i>Dubosiella</i> enrichment and normalization of <i>Lachnospiraceae NK4A136 group</i>, <i>Akkermansia</i>, <i>Turicibacter</i>, and <i>Parabacteroides</i>. LEfSe identified 24 genera distinguishing IBD and control mice; post-FMT microbiota of high-abundance donor recipients more closely resembled controls, correlating with therapeutic success.<h4>Conclusion</h4>FMT ameliorated IBD symptoms in murine models, with therapeutic efficacy associated with the relative abundance of health-associated microbial genera in donor microbiota.2025-01-01T00:00:00Z20252026-05-01T03:31:08.095Z2026-04-07T16:34:43.704ZS-EPMC123537334082182010.3389/fimmu.2025.1635244