Fecal Microbiota Transplantation Induces Sustained Gut Microbiome Changes in Pediatric Ulcerative Colitis: A Combined Randomized and Open-Label Study.

BACKGROUND AND AIMS

Fecal microbiota transplantation (FMT) is a promising tool to modulate the gut microbiome in pediatric ulcerative colitis (UC). We investigated the long-term impact of FMT on the gut microbiome and identified microbial signatures associated with disease severity and clinical outcomes.

METHODS

This study combined a randomized, double-blind trial comparing FMT to autologous placebo with an open-label extension to assess FMT's effects on the gut microbiome in pediatric UC patients over 48 weeks. Stool samples were collected at baseline and postintervention, and clinical response was evaluated using the Pediatric Ulcerative Colitis Activity Index. Shotgun metagenomic sequencing characterized the fecal microbiome's composition and functional potential. Taxon set enrichment analysis identified microbial taxon sets associated with UC and FMT.

RESULTS

FMT induced significant, sustained increases in gut microbial diversity over 48 weeks. Key changes included decreases in and increases in post-FMT. Microbial signatures were associated with disease severity, including increased indole producers and decreased mucin degraders in mild UC compared to remission. Patients with clinical improvement post-FMT showed decreased and . and decreased after open-label FMT.

CONCLUSION

FMT induces sustained changes in the pediatric UC gut microbiome, with distinct microbial signatures associated with disease severity and clinical outcomes. However, the high autologous placebo response rate underscores the need for further research to elucidate the mechanisms underlying FMT and placebo responses. Our study provides insights into the gut microbiome's role in pediatric UC, laying the foundation for developing personalized microbiome-targeted therapies. ClinicalTrials.gov number, NCT02291523.