Effects of Gut Microbiota and Metabolites on Pancreatitis: A Two-Sample Mendelian Randomization Study.

Abstract

Acute and chronic pancreatitis (AP and CP) has a high incidence and poor prognosis. The early screening of at-risk populations still awaits further study. The limitation was mainly based on observational studies, with limited sample size and the presence of confounding factors. We used a two sample MR analysis based on publicly available data from Genome-Wide Association Studies (GWAS) to reveal the causal impact of gut microbiota and metabolites on pancreatitis. This study collected summary statistics regarding gut microbiota, metabolites, AP, and CP. Two-sample Mendelian randomization analysis was performed using MR-Egger, inverse variance weighted (IVW), MR-PRESSO, maximum likelihood, and weighted median. Two sample Mendelian randomization showed that only Eubacterium coprostanoligenes was an independent protective factor for AP among all gut microbiota, and the other microbiota were not significant for pancreatitis. Unsaturated fatty acids in metabolites are protective factors for both AP (OR=0.730, 95% Cl: 0.593-0.899, P = 0.003) and CP (OR=0.660, 95% Cl: 0.457-0.916, P = 0.013). Furthermore, carnitine was a protective factor but glucose was an independent risk factor for CP. This study provides for the first-time potential evidence which is the causal role of gut microbiota and metabolites on pancreatitis, which may be conducive to design microbiome and metabolite interventions on AP or CP in profound study in the future.