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

Abstract

Several observational studies have reported a correlation between the gut microbiota (GM) and the risk of acute pancreatitis (AP). However, the causal relationship between them remains uncertain. We conducted a 2-sample Mendelian randomization (MR) study using pooled data from genome-wide association studies of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) and AP patients. We evaluated the causal relationship between the GM and AP using methods such as inverse-variance weighting, MR-Egger, weighted medians, simple mode, and weighted mode. Cochran Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to examine the heterogeneity, multipotency, and outlier values of the variables, respectively. The reverse causal relationship between AP and the GM was assessed with reverse MR. In total, 5 gut microbial taxa were significantly associated with AP. The inverse-variance weighting results indicated that Acidaminococcaceae (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.66–1.00, P = .045) and Ruminococcaceae UCG004 (OR: 0.85, 95% CI: 0.72–0.99, P = .040) were protective factors against the occurrence of AP. Coprococcus 3 (OR: 1.32, 95% CI: 1.03–1.70, P = .030), Eisenbergiella (OR: 1.13, 95% CI: 1.00–1.28, P = .043), and the Eubacterium fissicatena group (OR: 1.18, 95% CI: 1.05–1.33, P = .006) were risk factors for the development of AP. A comprehensive sensitivity analysis proved our results to be reliable. Reverse MR analysis did not indicate any causal relationship between AP and the GM. This study revealed a complex causal relationship between 5 GM taxa and AP, providing new insights into the diagnostic and therapeutic potential of the GM in AP patients.