The causal relationship between the gut microbiota and acute pancreatitis: A 2-sample Mendelian randomization study

Area of Science:

• Gastroenterology
• Microbiology
• Genetics

Background:

• Observational studies suggest a link between gut microbiota (GM) and acute pancreatitis (AP) risk.
• The causal relationship between GM and AP remains unclear, necessitating further investigation.

Purpose of the Study:

• To investigate the causal relationship between gut microbiota composition and the risk of acute pancreatitis using a 2-sample Mendelian randomization approach.
• To identify specific gut microbial taxa causally associated with AP development.

Main Methods:

• Utilized a 2-sample Mendelian randomization study with pooled genome-wide association study data for 211 gut microbial taxa and AP patients.
• Employed various statistical methods including inverse-variance weighting, MR-Egger, and weighted medians for causal inference.
• Performed sensitivity analyses (Cochran Q test, MR-Egger intercept, MR-PRESSO) to assess heterogeneity, pleiotropy, and outliers.
• Conducted reverse Mendelian randomization to evaluate potential reverse causality.

Main Results:

• Identified 5 gut microbial taxa significantly associated with AP risk.
• Acidaminococcaceae and Ruminococcaceae UCG004 showed a protective effect against AP (OR < 1).
• Coprococcus 3, Eisenbergiella, and the Eubacterium fissicatena group were identified as risk factors for AP (OR > 1).
• Sensitivity analyses confirmed the reliability of the findings, and reverse MR analysis found no evidence of reverse causality.

Conclusions:

• Established a complex causal relationship between specific gut microbiota taxa and acute pancreatitis.
• Findings suggest potential diagnostic and therapeutic targets within the gut microbiota for managing AP.
• Highlights the importance of considering gut microbial dysbiosis in the context of acute pancreatitis.