Interaction between Acute Pancreatitis and Gastrointestinal Microbiome: A Bidirectional Two-sample Mendelian Randomization Study

Abstract Background: Previous studies have shown that the severity of acute pancreatitis correlates with the gastrointestinal microbiome and that the development of acute pancreatitis causes changes in the gastrointestinal microbiome. However, there is no known genetic mechanism of action to explain the relationship between acute pancreatitis and the gastrointestinal microbiome. Methods: We performed a two-sample MR analysis of publicly available GWAS data on the gastrointestinal microbiome and acute pancreatitis. We applied several MR methods to explore causal associations, including inverse variance weights, weighted medians, MR‒Egger, Wald ratios, and MR-PRESSO. Sensitivity analyses and Cochrane's Q tests were also performed to exclude the effects of pleiotropy and heterogeneity. Results: IVW showed that enrichment of the Eubacterium rectale group, Holdemania and Terrisporobacter was correlated with the severity of acute pancreatitis. Inverse MR analyses revealed that the acute pancreatitis affected the abundance of Allisonella, Anaerotruncus, Paraprevotella, Erysipelotrichaceae UCG003, Family XIII AD3011 group, Haemophilus, Intestinibacter, Turicibacter and Tyzzerella 3. Conclusions: This study elucidates the association between acute pancreatitis and gastrointestinal microbiome at the level of genetic variation, but the mechanism of action needs to be further explored.