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

作者全名："Zhai, Qilong; Wu, Hongyu; Zheng, Siyuan; Zhong, Tao; Du, Changjie; Yuan, Jiajun; Peng, Jialun; Cai, Can; Li, Jinzheng"

作者地址："[Zhai, Qilong; Wu, Hongyu; Zheng, Siyuan; Zhong, Tao; Du, Changjie; Yuan, Jiajun; Peng, Jialun; Li, Jinzheng] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing, Peoples R China; [Cai, Can] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing, Peoples R China"

通信作者："Li, JZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing, Peoples R China.; Cai, C (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing, Peoples R China."

来源：FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001169074200001

JCR分区：Q2

影响因子：5.7

年份：2023

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; gut microbiota; Mendelian randomization; causality

摘要："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."

基金机构：Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University; Senior Medical Talents Program of Chongqing for Young and Middle-aged; Joint project of Chongqing Health Commission and Science and Technology Bureau; Natural Science Foundation of Chongqing [2022GDRC004]; [CSTB2022NSCQ-MSX1235]

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Funding for the study was provided by the Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University (JL), Senior Medical Talents Program of Chongqing for Young and Middle-aged (JL), Joint project of Chongqing Health Commission and Science and Technology Bureau (NO:2022GDRC004, JL) and Natural Science Foundation of Chongqing (NO: CSTB2022NSCQ-MSX1235, CC)."