Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study

ObjectiveThere is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no studies have explored their causal relationship.MethodsInstrumental variables of the gut microbiota (N = 13266) and gut m...

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Main Authors: Lilong Zhang, Liuliu Zi, Tianrui Kuang, Kunpeng Wang, Zhendong Qiu, Zhongkai Wu, Li Liu, Rongqiang Liu, Peng Wang, Weixing Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1159148/full
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author Lilong Zhang
Lilong Zhang
Lilong Zhang
Liuliu Zi
Liuliu Zi
Liuliu Zi
Tianrui Kuang
Tianrui Kuang
Tianrui Kuang
Kunpeng Wang
Kunpeng Wang
Kunpeng Wang
Zhendong Qiu
Zhendong Qiu
Zhendong Qiu
Zhongkai Wu
Zhongkai Wu
Zhongkai Wu
Li Liu
Li Liu
Li Liu
Rongqiang Liu
Rongqiang Liu
Rongqiang Liu
Peng Wang
Peng Wang
Peng Wang
Weixing Wang
Weixing Wang
Weixing Wang
author_facet Lilong Zhang
Lilong Zhang
Lilong Zhang
Liuliu Zi
Liuliu Zi
Liuliu Zi
Tianrui Kuang
Tianrui Kuang
Tianrui Kuang
Kunpeng Wang
Kunpeng Wang
Kunpeng Wang
Zhendong Qiu
Zhendong Qiu
Zhendong Qiu
Zhongkai Wu
Zhongkai Wu
Zhongkai Wu
Li Liu
Li Liu
Li Liu
Rongqiang Liu
Rongqiang Liu
Rongqiang Liu
Peng Wang
Peng Wang
Peng Wang
Weixing Wang
Weixing Wang
Weixing Wang
author_sort Lilong Zhang
collection DOAJ
description ObjectiveThere is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no studies have explored their causal relationship.MethodsInstrumental variables of the gut microbiota (N = 13266) and gut microbiota-derived metabolites (N = 7824) were acquired, and a Mendelian randomization study was performed to explore their influence on NAFLD (1483 European cases and 17,781 European controls), ALD (2513 European cases and 332,951 European controls), and viral hepatitis risk (1971 European cases and 340,528 European controls). The main method for examining causality is inverse variance weighting (IVW).ResultsIVW results confirmed that Anaerotruncus (p = 0.0249), Intestinimonas (p = 0.0237), Lachnoclostridium (p = 0.0245), Lachnospiraceae NC2004 group (p = 0.0083), Olsenella (p = 0.0163), and Peptococcus (p = 0.0472) were protective factors for NAFLD, and Ruminococcus 1 (p = 0.0120) was detrimental for NAFLD. The higher abundance of three genera, Lachnospira (p = 0.0388), Desulfovibrio (p = 0.0252), and Ruminococcus torques group (p = 0.0364), was correlated with a lower risk of ALD, while Ruminococcaceae UCG 002 level was associated with a higher risk of ALD (p = 0.0371). The Alistipes (p = 0.0069) and Ruminococcaceae NK4A214 group (p = 0.0195) were related to a higher risk of viral hepatitis. Besides, alanine (p = 0.0076) and phenyllactate (p = 0.0100) were found to be negatively correlated with NAFLD, while stachydrine (Op = 0.0244) was found to be positively associated with NAFLD. The phenylacetate (p = 0.0353) and ursodeoxycholate (p = 0.0144) had a protective effect on ALD, while the threonate (p = 0.0370) exerted a detrimental influence on ALD. The IVW estimates of alanine (p = 0.0408) and cholate (p = 0.0293) showed their suggestive harmful effects against viral hepatitis, while threonate (p = 0.0401) displayed its suggestive protective effect against viral hepatitis.ConclusionIn conclusion, our research supported causal links between the gut microbiome and its metabolites and NAFLD, ALD, and viral hepatitis.
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spelling doaj.art-500bfb7e0aac47668bd479a7f8c0c6772023-07-05T17:51:40ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-07-011410.3389/fendo.2023.11591481159148Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization studyLilong Zhang0Lilong Zhang1Lilong Zhang2Liuliu Zi3Liuliu Zi4Liuliu Zi5Tianrui Kuang6Tianrui Kuang7Tianrui Kuang8Kunpeng Wang9Kunpeng Wang10Kunpeng Wang11Zhendong Qiu12Zhendong Qiu13Zhendong Qiu14Zhongkai Wu15Zhongkai Wu16Zhongkai Wu17Li Liu18Li Liu19Li Liu20Rongqiang Liu21Rongqiang Liu22Rongqiang Liu23Peng Wang24Peng Wang25Peng Wang26Weixing Wang27Weixing Wang28Weixing Wang29Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaObjectiveThere is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no studies have explored their causal relationship.MethodsInstrumental variables of the gut microbiota (N = 13266) and gut microbiota-derived metabolites (N = 7824) were acquired, and a Mendelian randomization study was performed to explore their influence on NAFLD (1483 European cases and 17,781 European controls), ALD (2513 European cases and 332,951 European controls), and viral hepatitis risk (1971 European cases and 340,528 European controls). The main method for examining causality is inverse variance weighting (IVW).ResultsIVW results confirmed that Anaerotruncus (p = 0.0249), Intestinimonas (p = 0.0237), Lachnoclostridium (p = 0.0245), Lachnospiraceae NC2004 group (p = 0.0083), Olsenella (p = 0.0163), and Peptococcus (p = 0.0472) were protective factors for NAFLD, and Ruminococcus 1 (p = 0.0120) was detrimental for NAFLD. The higher abundance of three genera, Lachnospira (p = 0.0388), Desulfovibrio (p = 0.0252), and Ruminococcus torques group (p = 0.0364), was correlated with a lower risk of ALD, while Ruminococcaceae UCG 002 level was associated with a higher risk of ALD (p = 0.0371). The Alistipes (p = 0.0069) and Ruminococcaceae NK4A214 group (p = 0.0195) were related to a higher risk of viral hepatitis. Besides, alanine (p = 0.0076) and phenyllactate (p = 0.0100) were found to be negatively correlated with NAFLD, while stachydrine (Op = 0.0244) was found to be positively associated with NAFLD. The phenylacetate (p = 0.0353) and ursodeoxycholate (p = 0.0144) had a protective effect on ALD, while the threonate (p = 0.0370) exerted a detrimental influence on ALD. The IVW estimates of alanine (p = 0.0408) and cholate (p = 0.0293) showed their suggestive harmful effects against viral hepatitis, while threonate (p = 0.0401) displayed its suggestive protective effect against viral hepatitis.ConclusionIn conclusion, our research supported causal links between the gut microbiome and its metabolites and NAFLD, ALD, and viral hepatitis.https://www.frontiersin.org/articles/10.3389/fendo.2023.1159148/fullalcoholic liver diseasenonalcoholic fatty liver diseaseviral hepatitisgut microbiotagut microbiota-derived metabolitesmendelian randomization analysis
spellingShingle Lilong Zhang
Lilong Zhang
Lilong Zhang
Liuliu Zi
Liuliu Zi
Liuliu Zi
Tianrui Kuang
Tianrui Kuang
Tianrui Kuang
Kunpeng Wang
Kunpeng Wang
Kunpeng Wang
Zhendong Qiu
Zhendong Qiu
Zhendong Qiu
Zhongkai Wu
Zhongkai Wu
Zhongkai Wu
Li Liu
Li Liu
Li Liu
Rongqiang Liu
Rongqiang Liu
Rongqiang Liu
Peng Wang
Peng Wang
Peng Wang
Weixing Wang
Weixing Wang
Weixing Wang
Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study
Frontiers in Endocrinology
alcoholic liver disease
nonalcoholic fatty liver disease
viral hepatitis
gut microbiota
gut microbiota-derived metabolites
mendelian randomization analysis
title Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study
title_full Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study
title_fullStr Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study
title_full_unstemmed Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study
title_short Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study
title_sort investigating causal associations among gut microbiota metabolites and liver diseases a mendelian randomization study
topic alcoholic liver disease
nonalcoholic fatty liver disease
viral hepatitis
gut microbiota
gut microbiota-derived metabolites
mendelian randomization analysis
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1159148/full
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