Causal effects between gut microbiology and hyperlipidemia: A 2-sample Mendelian randomization study

Recent studies have confirmed the connection between gut microbiota (GM) and hyperlipidemia. This study used the Mendelian randomization (MR) technique to explore the association between GM and hyperlipidemia. MR was used to examine data derived from a genome-wide association study that combined data from 211 intestinal microbiota and hyperlipidemia. Five statistical tools were used for statistical analyses, including the MR-Egger method, the weighted median method, the inverse variance weighted method, the simple model, and the weighted mode. Inverse variance weighted is the main type among them. The robustness of the results was then assessed using Cochran's Q, MR-Egger regression, and MR pleiotropy residual sum and outlier tests. The results revealed that hyperlipidemia is associated with 9 intestinal microbiotas. This included harmful bacteria, such as Enterobacteriaceae (odds ratio [OR] = 1.307, 95% confidence interval [CI]: 1.054-1.621, P = .015), Adlercreutzia (OR = 1.254, 95% CI: 1.069-1.470, P = .005, LachnospiraceaeUCG001 (OR = 1.201, 95% CI: 1.004-1.446, P = .045), Ruminococcus1 (OR = 1.224, 95% CI: 1.010-1.483, P = .039), and Enterobacteriales (OR = 1.307, 95% CI: 1.054-1.621, P = .015). They had a certain association with the pathogenesis of hyperlipidemia. They increased the risk of developing hyperlipidemia and were positively correlated with its onset. Oxalobacteraceae (OR = 0.897, 95% CI: 0.804-1.000, P = .049), Clostridiumsensustricto1 (OR = 0.728, 95% CI: 0.594-0.894, P = .002), RuminococcaceaeUCG010 (OR = 0.792, 95% CI: 0.628-0.999, P = .049), and Rhodospirillales (OR = 0.846, 95% CI: 0.733-0.977, P = .022) may have reduced the risk of developing hyperlipidemia and were negatively correlated with its onset. Furthermore, there was no evidence of a causal relationship between hyperlipidemia and the intestinal flora. The heterogeneity test, pleiotropy test, and sensitivity analysis did not detect any significant heterogeneity or pleiotropy effects. This study was the first to use the MR method to reveal the potential causal relationship between GM and hyperlipidemia and indicated no bidirectional causal effect. The microbiota information provides new insights for further research on improving the onset and prognosis of hyperlipidemia.