Investigating Causal Links between Metabolite Profiles and Ulcerative Colitis: A Bidirectional Mendelian...

Area of Science:

• Genetics
• Metabolomics
• Gastroenterology

Background:

• Ulcerative colitis (UC) development is influenced by metabolic biomarkers, but causal links remain unclear.
• Investigating the relationship between blood metabolites and UC is crucial for understanding disease mechanisms.

Purpose of the Study:

• To evaluate the causal relationships between 503 blood metabolites and ulcerative colitis (UC) using a bidirectional Mendelian randomization study.
• To identify potential metabolic biomarkers for UC screening, prevention, and therapeutic target discovery.

Main Methods:

• Utilized genome-wide association study (GWAS) data for 503 blood metabolites and UC from European ancestry cohorts.
• Employed inverse variance weighted (IVW) method for primary analysis and various sensitivity analyses (MR-Egger, weighted median) to ensure robustness.

Main Results:

• A marginal significant positive association was observed between total lipids in small high-density lipoprotein levels (S.HDL.L) and UC development (OR = 1.167, P = 0.051).
• No statistically significant causal effect of UC on the studied metabolites was detected.

Conclusions:

• Total lipids in S.HDL.L may serve as a potential circulating biomarker for UC screening and prevention.
• These lipids could be candidate molecules for elucidating UC pathogenesis and identifying drug targets.