Mechanistic insights into fecal microbiota transplantation for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial.

Colonic FMT delivery was superior to nasogastric delivery for clinical response at week 8 in ulcerative colitis patients.

• Clinical response rate at week 8 was 75% (9/12) for colonic FMT versus 25% (2/8) for nasogastric FMT in per-protocol analysis.
• Risk ratio was 2.94 (95% CI 0.84–10.30) favoring colonic delivery.
• The trial was a prospective, open-label, randomized pilot trial (STOP-Colitis) with 30 adults with active ulcerative colitis.
• Patients were randomized to receive multidose FMT via nasogastric tube or colonoscopy with subsequent enemas.

Clinical response to FMT was associated with successful microbial engraftment and significantly increased fecal microbial diversity.

• Responders showed enrichment of SCFA-producing taxa, including Oscillospiraceae and Christensenellaceae.
• Microbial composition was assessed using both 16S rRNA and shotgun metagenomics.
• Increased fecal microbial diversity correlated with reduced fecal calprotectin in responders.
• Multi-omic analyses of stool and biopsies were conducted longitudinally.

FMT responders showed a significant increase in mucosal regulatory T cells and concurrent decreases in pro-inflammatory T cell populations.

• Mucosal regulatory T cells were significantly increased in responders (P = .01).
• Th17 cells showed a significant concurrent decrease in responders (P = 0.03).
• CD8+ T cells also decreased in responders.
• Mucosal T-cell analysis was performed on biopsy samples as part of the multi-omic longitudinal analyses.

Mucosal transcriptomics confirmed an anti-inflammatory shift in FMT responders, with upregulation of metabolic pathways and downregulation of proinflammatory defense pathways.

• Host gene expression analysis was performed on mucosal biopsies.
• Responders showed upregulation of metabolic pathways.
• Responders showed downregulation of proinflammatory defense pathways.
• These transcriptomic findings were consistent with the immunological changes observed in mucosal T-cell analyses.

Short-chain fatty acids (SCFAs) were measured as part of the mechanistic analysis, with SCFA-producing taxa enriched in responders.

• SCFA production was assessed in stool samples as part of longitudinal multi-omic analyses.
• Enrichment of SCFA-producing taxa including Oscillospiraceae and Christensenellaceae was observed in responders.
• SCFA changes correlated with reduced fecal calprotectin.
• SCFA analysis was conducted alongside 16S rRNA, shotgun metagenomics, mucosal T-cell, and host gene expression analyses.