A bidirectional two-sample Mendelian randomization using the gut microbiota to reveal potential therapeutic targets for acute pancreatitis

Author:

He Lin1,Luo Haojun2,Li Yu1,Lu Jing1,Li Jinzhi1,Peng Li1,Xu Yan1,Liu Hang1

Affiliation:

1. People’s Hospital of Deyang City

2. The Second Affiliated Hospital of Chongqing Medical University

Abstract

Abstract

Background: Numerous studies have indicated a correlation between the gut microbiota (GM) and acute pancreatitis (AP), yet the precise causal relationship between them remains ambiguous. Methods: A two-sample Mendelian randomization (MR) study was conducted utilizing aggregated data from genome-wide association studies (GWASs) of 471 taxa (11 phyla, 19 orders, 24 orders, 62 families, 146 genera, and 209 species) and AP patients. Various methods, including inverse variance weighting (IVW), MR‒Egger, weighted medians, simple mode, and weighted mode, were employed to assess the causal association between the GM and AP. Sensitivity analyses were conducted utilizing Cochran's Q test, MR-Egger regression intercept analysis, and MR-PRESSO, followed by reverse MR analysis to evaluate the potential reverse causality between AP and GM. Results: Three gut microbial taxa were found to have significant associations with acute pancreatitis (AP). The inverse variance weighted (IVW) results revealed that Coprobacillus (OR 1.19, 95% CI 1.01 to 1.40, p=0.035) and Holdemania sp900120005 (OR 1.18, 95% CI 1.02 to 1.35, p=0.023) were identified as risk factors for the development of AP, while Megamonas (OR: 0.87, 95% CI: 0.77 to 0.98, p=0.023) was found to be a protective factor against the occurrence of AP. A thorough sensitivity analysis confirmed the reliability of our findings. Reverse Mendelian randomization (MR) analysis did not indicate any causal relationship between AP and the gut microbiota (GM). Conclusions: This study revealed a complex causal relationship between 3 GM taxa and AP, providing new evidence for the development of AP from a genetic perspective.

Publisher

Research Square Platform LLC

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