AUTHOR=Zhai Qilong , Wu Hongyu , Zheng Siyuan , Zhong Tao , Du Changjie , Yuan Jiajun , Peng Jialun , Cai Can , Li Jinzheng 

TITLE=Association between gut microbiota and NAFLD/NASH: a bidirectional two-sample Mendelian randomization study

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1294826

DOI=10.3389/fcimb.2023.1294826

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>Recent studies have suggested a relationship between gut microbiota and non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the nature and direction of this potential causal relationship are still unclear. This study used two-sample Mendelian randomization (MR) to clarify the potential causal links.</p></sec><sec><title>Methods</title><p>Summary-level Genome-Wide Association Studies (GWAS) statistical data for gut microbiota and NAFLD/NASH were obtained from MiBioGen and FinnGen respectively. The MR analyses were performed mainly using the inverse-variance weighted (IVW) method, with sensitivity analyses conducted to verify the robustness. Additionally, reverse MR analyses were performed to examine any potential reverse causal associations.</p></sec><sec><title>Results</title><p>Our analysis, primarily based on the IVW method, strongly supports the existence of causal relationships between four microbial taxa and NAFLD, and four taxa with NASH. Specifically, associations were observed between Enterobacteriales (<italic>P</italic> =0.04), <italic>Enterobacteriaceae</italic> (<italic>P</italic> =0.04), <italic>Lachnospiraceae UCG-004</italic> (<italic>P</italic> =0.02), and <italic>Prevotella9</italic> (<italic>P</italic> =0.04) and increased risk of NAFLD. <italic>Dorea</italic> (<italic>P</italic> =0.03) and <italic>Veillonella</italic> (<italic>P</italic> =0.04) could increase the risks of NASH while <italic>Oscillospira</italic> (<italic>P</italic> =0.04) and <italic>Ruminococcaceae UCG-013</italic> (<italic>P</italic>=0.005) could decrease them. We also identified that NAFLD was found to potentially cause an increased abundance in <italic>Holdemania</italic> (<italic>P</italic> =0.007) and <italic>Ruminococcus2</italic> (<italic>P</italic> =0.002). However, we found no evidence of reverse causation in the microbial taxa associations with NASH.</p></sec><sec><title>Conclusion</title><p>This study identified several specific gut microbiota that are causally related to NAFLD and NASH. Observations herein may provide promising theoretical groundwork for potential prevention and treatment strategies for NAFLD and its progression to NASH in future.</p></sec>