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Related Experiment Video

Updated: Jul 8, 2025

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

Qilong Zhai1, Hongyu Wu1, Siyuan Zheng1

  • 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Frontiers in Cellular and Infection Microbiology
|December 18, 2023
PubMed
Summary

This study reveals causal links between specific gut bacteria and non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Findings may guide future prevention and treatment strategies for these liver conditions.

Keywords:
Mendelian randomizationcausalitygut microbiotanon-alcoholic fatty liver diseasenon-alcoholic steatohepatitis

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Area of Science:

  • Gastroenterology and Hepatology
  • Microbiome Research
  • Genetic Epidemiology

Background:

  • Emerging evidence suggests a connection between gut microbiota composition and the development of non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).
  • The precise nature and directionality of the causal relationship between gut microbes and NAFLD/NASH remain largely undetermined.

Purpose of the Study:

  • To elucidate the potential causal associations between specific gut microbial taxa and the risk of NAFLD and NASH.
  • To investigate the directionality of these relationships using Mendelian randomization.

Main Methods:

  • Employed two-sample Mendelian randomization (MR) utilizing summary-level Genome-Wide Association Studies (GWAS) data for gut microbiota (MiBioGen) and NAFLD/NASH (FinnGen).
  • Inverse-variance weighted (IVW) method was the primary analytical approach, supplemented by sensitivity analyses and reverse MR to ensure robustness and explore reverse causality.

Main Results:

  • Identified causal links between four microbial taxa and NAFLD, and four taxa with NASH.
  • Specific taxa like Enterobacteriales, Enterobacteriaceae, Lachnospiraceae UCG-004, and Prevotella9 were associated with increased NAFLD risk.
  • Dorea and Veillonella were linked to increased NASH risk, while Oscillospira and Ruminococcaceae UCG-013 were associated with decreased NASH risk.
  • NAFLD was found to potentially increase the abundance of Holdemania and Ruminococcus2, with no evidence of reverse causation for NASH.

Conclusions:

  • This study provides robust evidence for causal relationships between several specific gut microbes and NAFLD/NASH.
  • These findings offer a theoretical foundation for developing novel strategies for the prevention and treatment of NAFLD and its progression to NASH.