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

OBJECTIVE: There 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. METHODS: Instrumental variables of the gut microbiota (N = 13266) and...

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Autores principales: Zhang, Lilong, Zi, Liuliu, Kuang, Tianrui, Wang, Kunpeng, Qiu, Zhendong, Wu, Zhongkai, Liu, Li, Liu, Rongqiang, Wang, Peng, Wang, Weixing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354516/
https://www.ncbi.nlm.nih.gov/pubmed/37476494
http://dx.doi.org/10.3389/fendo.2023.1159148
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author Zhang, Lilong
Zi, Liuliu
Kuang, Tianrui
Wang, Kunpeng
Qiu, Zhendong
Wu, Zhongkai
Liu, Li
Liu, Rongqiang
Wang, Peng
Wang, Weixing
author_facet Zhang, Lilong
Zi, Liuliu
Kuang, Tianrui
Wang, Kunpeng
Qiu, Zhendong
Wu, Zhongkai
Liu, Li
Liu, Rongqiang
Wang, Peng
Wang, Weixing
author_sort Zhang, Lilong
collection PubMed
description OBJECTIVE: There 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. METHODS: Instrumental 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). RESULTS: IVW 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. CONCLUSION: In conclusion, our research supported causal links between the gut microbiome and its metabolites and NAFLD, ALD, and viral hepatitis.
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spelling pubmed-103545162023-07-20 Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study Zhang, Lilong Zi, Liuliu Kuang, Tianrui Wang, Kunpeng Qiu, Zhendong Wu, Zhongkai Liu, Li Liu, Rongqiang Wang, Peng Wang, Weixing Front Endocrinol (Lausanne) Endocrinology OBJECTIVE: There 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. METHODS: Instrumental 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). RESULTS: IVW 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. CONCLUSION: In conclusion, our research supported causal links between the gut microbiome and its metabolites and NAFLD, ALD, and viral hepatitis. Frontiers Media S.A. 2023-07-05 /pmc/articles/PMC10354516/ /pubmed/37476494 http://dx.doi.org/10.3389/fendo.2023.1159148 Text en Copyright © 2023 Zhang, Zi, Kuang, Wang, Qiu, Wu, Liu, Liu, Wang and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Zhang, Lilong
Zi, Liuliu
Kuang, Tianrui
Wang, Kunpeng
Qiu, Zhendong
Wu, Zhongkai
Liu, Li
Liu, Rongqiang
Wang, Peng
Wang, Weixing
Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study
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 Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354516/
https://www.ncbi.nlm.nih.gov/pubmed/37476494
http://dx.doi.org/10.3389/fendo.2023.1159148
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