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. 2023 Dec 1:13:1294826.
doi: 10.3389/fcimb.2023.1294826. eCollection 2023.

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

Qilong Zhai #  1 , Hongyu Wu #  1 , Siyuan Zheng #  1 , Tao Zhong  1 , Changjie Du  1 , Jiajun Yuan  1 , Jialun Peng  1 , Can Cai  2 , Jinzheng Li  1
Affiliations

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

Qilong Zhai et al. Front Cell Infect Microbiol. .

Abstract

Background: 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.

Methods: 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.

Results: 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 (P =0.04), Enterobacteriaceae (P =0.04), Lachnospiraceae UCG-004 (P =0.02), and Prevotella9 (P =0.04) and increased risk of NAFLD. Dorea (P =0.03) and Veillonella (P =0.04) could increase the risks of NASH while Oscillospira (P =0.04) and Ruminococcaceae UCG-013 (P=0.005) could decrease them. We also identified that NAFLD was found to potentially cause an increased abundance in Holdemania (P =0.007) and Ruminococcus2 (P =0.002). However, we found no evidence of reverse causation in the microbial taxa associations with NASH.

Conclusion: 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.

Keywords: Mendelian randomization; causality; gut microbiota; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Three assumptions and flowchart of the MR analyses.
Figure 2
Figure 2
The illustration represents significant causal gut microbial taxa associated with NAFLD and NASH.
Figure 3
Figure 3
Forest plot of the associations between genetically determined gut microbial taxa with the risks of NAFLD.
Figure 4
Figure 4
The scatter plots for the causal association between gut microbial taxa and NAFLD.
Figure 5
Figure 5
The leave-one-out plots for the causal association between gut microbial taxa and NAFLD/NASH.
Figure 6
Figure 6
The Forest plot and Scatter plot of Reverse MR.
Figure 7
Figure 7
Forest plot of the associations between genetically determined gut microbial genera with the risks of NASH.
Figure 8
Figure 8
The scatter plots for the causal association between gut microbial taxa and NASH.
See this image and copyright information in PMC

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