Genome-wide Mendelian randomization study of the pathogenic role of gut microbiota in benign biliary tract diseases

Abstract

Objective: To investigate the causal relationship between intestinal flora and benign biliary diseases by genome-wide Mendelian randomization. Methods: This is a retrospective observational study. The data from the genome-wide association study of the gut microbiota from 18 340 samples from the MiBioGen consortium were selected as the exposure group,and the data from the genome-wide association study of biliary tract diseases were obtained from the FinnGen consortium R8 as the outcome group. There were 1 491 cases of primary sclerosing cholangitis,32 894 cases of cholelithiasis,3 770 cases of acalculous cholecystitis,and 34 461 cases of cholecystitis. Single nucleotide polymorphisms were screened as instrumental variables,and the Mendelian randomization method was used to infer the causal relationship between exposures and outcomes. The inverse variance weighting method (IVW) was used as the main basis, supplemented by heterogeneity,pleiotropy and sensitivity tests. Results: Coprococcus 2 was associated with a reduced risk of cholelithiasis (IVW OR=0.88,95%CI:0.80 to 0.97,P=0.012) and cholecystitis (IVW OR=0.88,95%CI:0.80 to 0.97,P=0.011). Coprococcus 3 was associated with cholelithiasis (IVW OR=1.15,95%CI:1.02 to 1.30,P=0.019) and acalculous cholecystitis(IVW OR=1.48, 95%CI: 1.08 to 2.04,P=0.016) and cholecystitis (IVW OR=1.17, 95%CI: 1.02 to 1.33, P=0.020). Peptococcus was associated with an increased risk of cholelithiasis (IVW OR=1.08, 95%CI:1.02 to 1.13, P=0.005) and cholecystitis (IVW CI=1.07, 95%CI:1.02 to 1.13,P=0.010). Clostridiumsensustricto 1 was associated with an increased risk of cholelithiasis (IVW OR=1.16,95%CI:1.02 to 1.31, P=0.020) and cholecystitis (IVW OR=1.16, 95%CI:1.03 to 1.30, P=0.015). Eubacterium hallii was associated with an increased risk of primary sclerosing cholangitis (IVW OR=1.43, 95%CI: 1.03 to 1.99, P=0.033). Eubacterium ruminantium (IVW OR=0.87, 95%CI: 0.76 to 1.00, P=0.043) and Methanobrevibacter (IVW OR=0.81, 95%CI: 0.68 to 0.98, P=0.027) were associated with a reduced risk of acalculous cholecystitis. Conclusions: Eight intestinal bacterial genera maybe play pathogenic roles in benign biliary diseases. Eubacterium hallii can increase the risk of primary sclerosing cholangitis. Peptococcus and Clostridiumsensustricto 1 can increase the risk of cholelithiasis and generalized cholecystitis. Coprococcus 3 have multiple correlations with biliary stones and inflammation.