The Causal Relationship between Gut Microbiota and Non-alcoholic Fatty Liver Disease: A Mendelian Randomization Study

Abstract Aims The association between the gut microbiota and non-alcoholic fatty liver disease (NAFLD) has been documented; however, the causal relationship between them remains unclear. The aim of this study was to explore the causal relationship between the gut microbiota and NAFLD using Mendelian randomization. Methods We conducted a Mendelian randomization study, using gut microbiota data (n = 18340) from MiBioGen consortium as the exposure and the NAFLD dataset from FinnGen R9 release data (n = 377,277) as the outcome. Inverse variance weighted was employed as the primary analysis method, and sensitivity analysis was performed. Additionally, a network graph resembling a phylogenetic tree was created to further reveal the evolutionary relationships among gut microbiota. Results Six bacterial features exhibited causal relationships with NAFLD: Actinomycetales (OR = 1.50, 95% CI: 1.01–2.21, p = 0.043), Actinomycetaceae (OR = 1.49, 95% CI: 1.01–2.20, p = 0.043), Actinomyces (OR = 1.36, 95% CI: 1.09–1.71, p = 0.006), Prevotella 7 (OR = 1.19, 95% CI: 1.01–1.39, p = 0.039) exhibited potential detrimental effects on NAFLD, whereas Anaerofilum (OR = 0.85, 95% CI: 0.72–0.99, p = 0.042) and Gordonibacter (OR = 0.84, 95% CI: 0.72–0.98, p = 0.024) exhibited potential protective effects. Furthermore, Actinomycetales, Actinomycetaceae, and Actinomyces are located on the same evolutionary branch. Conclusions Our study revealed a causal relationship between six gut bacteria and NAFLD. These findings shed light on the role of specific gut bacteria in the pathogenesis of NAFLD and offer valuable insights into future therapeutic interventions and preventive strategies.