Efficacy of Oral Vancomycin in PSC-IBD: Clinical Remission and Microbiome Changes

Overview

In a single-arm study of 15 patients with primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD), oral vancomycin induced clinical remission in 12 patients after 4 weeks of treatment. This remission correlated with significant reductions in fecal calprotectin and distinct shifts in gut microbiota composition, metatranscriptomic pathways, and metabolomic profiles.

Background

PSC is a chronic liver disease frequently associated with colonic IBD, leading to increased risks of colorectal cancer and liver-related morbidity. The pathogenesis of PSC-IBD involves immune dysregulation, gut microbial alterations, and bile acid homeostasis disturbances. Prior observational studies suggested that oral vancomycin, a non-absorbable antibiotic, may reduce biochemical markers of PSC and induce remission in PSC-IBD, but mechanistic insights have been limited. This study aimed to explore mucosal, microbial, and metabolomic changes associated with clinical remission induced by oral vancomycin in PSC-IBD patients.

Data Highlights

Key Findings

• Oral vancomycin induced clinical remission in 12 out of 15 PSC-IBD patients after 4 weeks of treatment.
• Fecal calprotectin levels significantly decreased during treatment, indicating reduced colonic inflammation.
• Gut microbiota composition shifted with decreased Lachnospiraceae, Blautia, and Bacteroides, and increased Enterobacteriaceae, Veillonella, Akkermansia, and Escherichia genera.
• Metatranscriptomic analysis revealed downregulation of pathways involved in short-chain fatty acid metabolism and bile acid biotransformation, alongside reduced host inflammatory and antimicrobial gene expression.
• Genes associated with extracellular matrix repair were upregulated during vancomycin treatment.
• Withdrawal of vancomycin led to relapse of colitis activity and reversal of microbial and host mucosal changes toward baseline.

Clinical Implications

Oral vancomycin shows promise as a therapeutic agent to induce remission in PSC-IBD by modulating gut microbiota and host inflammatory pathways. Monitoring fecal calprotectin can help assess treatment response. However, relapse after treatment cessation suggests the need for strategies to maintain remission or longer-term therapy. These findings support further investigation of microbiome-targeted therapies in PSC-IBD management.

Conclusion

Four weeks of oral vancomycin effectively induces remission in PSC-IBD patients, accompanied by significant shifts in gut microbial diversity and host mucosal biology related to bile acid and short-chain fatty acid metabolism. These results provide mechanistic insights into vancomycin’s therapeutic effects and highlight the dynamic interplay between microbiota and host in PSC-IBD.

References

1. NCT05376228 -- Efficacy of Oral Vancomycin in PSC-IBD Study