Gut-derived ImP may promote biliary injury

Overview

A gut microbiota-derived metabolite, imidazole propionate (ImP), is associated with the progression of primary sclerosing cholangitis (PSC) and poorer transplant-free survival. Experimental studies suggest that ImP may promote biliary injury through a specific signaling pathway involving p38 signaling.

Background

Primary sclerosing cholangitis is a fibroinflammatory cholangiopathy often linked with inflammatory bowel disease, and it lacks effective medical therapies to alter its course. Understanding the role of gut-derived metabolites like ImP in PSC progression could provide insights into the disease.

Data Highlights

Key Findings

• Higher circulating levels of ImP are linked to poorer transplant-free survival in PSC patients.
• ImP concentrations remain elevated post-liver transplantation, unlike healthy controls.
• Each doubling of ImP concentration correlates with an 18% increased hazard of recurrent PSC.
• ImP is associated with lower gut microbial diversity in PSC patients.
• Experimental studies indicate that ImP exposure increases proinflammatory and profibrotic factors in cholangiocyte organoids.

Clinical Implications

The findings indicate that further research is needed to understand the mechanisms by which ImP influences biliary injury.

Conclusion

Further research is warranted to explore the role of gut-derived ImP in PSC.

Related Resources & Content

1. Gut microbiota-derived imidazole propionate promotes primary sclerosing cholangitis via p38 signalling, Nature Metabolism, 2026 -- Gut-derived ImP may promote biliary injury
2. Infection — Investigating Gut Barrier Dysfunction's Impact on Postoperative Outcomes Following Liver Transplantation: Insights into Pathophysiology and Treatment Options
3. BJS (British Journal of Surgery) — Classification Framework for Biliary Complications Following Liver Transplantation: Recommendations from the BileducTx Conference
4. Journal of Gastrointestinal Surgery — The Impact of Intestinal-Derived Lipopolysaccharides and Gut Barrier Function on Fatty Liver Disorders
5. Journal of Gastrointestinal Surgery — Preoperative Biliary Drainage in Patients Experiencing Obstructive Jaundice: A Historical Perspective and Current Insights
6. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma
7. The 2024 diagnostic criteria for primary sclerosing cholangitis | Journal of Gastroenterology | Springer Nature Link
8. Primary sclerosing cholangitis
9. Cilofexor in non-cirrhotic primary sclerosing cholangitis (PRIMIS): a randomised, double-blind, multicentre, placebo-controlled, phase 3 trial - PubMed
10. Positive results from pivotal phase 3 trial on norucholic acid in PSC: Dr. Falk Pharma UK & Ireland
11. norUrsodeoxycholic acid improves cholestasis in primary sclerosing cholangitis - PubMed
12. Gut microbiota-derived imidazole propionate promotes primary sclerosing cholangitis via p38 signalling | Nature Metabolism
13. VOLUME 84 ISSUE 1, MAY 2026