Causal impact of gut microbiota on five liver diseases: insights from mendelian randomization and single-cell RNA sequencing

BackgroundLiver disease is among the top ten causes of death globally. With studies suggesting a link between gut microbiota (GM) and liver disease.MethodWe selected summary statistics data from the largest available whole-genome association study (n = 13,266) of GM by the MiBioGen consortium as the...

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Main Authors: Na Li, Xuanyi Chen, Shuai Xiong, Yuxin Cheng, Jiali Deng, Junli Zhang, Fei Yu, Liyuan Hao, Shenghao Li, Xiaoyu Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2024.1362139/full
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author Na Li
Na Li
Xuanyi Chen
Shuai Xiong
Shuai Xiong
Yuxin Cheng
Jiali Deng
Jiali Deng
Junli Zhang
Fei Yu
Fei Yu
Liyuan Hao
Liyuan Hao
Shenghao Li
Shenghao Li
Xiaoyu Hu
author_facet Na Li
Na Li
Xuanyi Chen
Shuai Xiong
Shuai Xiong
Yuxin Cheng
Jiali Deng
Jiali Deng
Junli Zhang
Fei Yu
Fei Yu
Liyuan Hao
Liyuan Hao
Shenghao Li
Shenghao Li
Xiaoyu Hu
author_sort Na Li
collection DOAJ
description BackgroundLiver disease is among the top ten causes of death globally. With studies suggesting a link between gut microbiota (GM) and liver disease.MethodWe selected summary statistics data from the largest available whole-genome association study (n = 13,266) of GM by the MiBioGen consortium as the exposure, and obtained liver disease-related data from IEU Open GWAS and The NHGRI-EBI GWAS Catalog. A two-sample Mendelian Randomization (MR) analysis employing various methods, to establish the causal relationship between GM and five liver diseases. Meanwhile, single-cell RNA sequencing data were used to examine Prevotella-related genes expression under healthy and disease liver.ResultsThe IVW analysis indicate a causal relationship between GM and liver diseases, with Prevotella exhibiting a protective effect in all five liver diseases: Alcoholic liver disease (OR:0.81,95% confidence interval:0.66-1.00,PIVW = 0.0494); Cirrhosis (OR: 0.85,95% confidence interval: 0.73-0.99,PIVW = 0.0397); Hepatic failure, not elsewhere classified (OR:0.60,95% confidence interval:0.37-0.95,PIVW = 0.0305); Benign neoplasm:Liver (OR:0.39,95% confidence interval:0.2-0.75,PIVW = 0.0046); Malignant neoplasm of liver, primary (OR:0.41, 95% confidence interval:0.18-0.93,PIVW = 0.0334). The single-cell results suggest differential expression of Prevotella-related genes between liver disease patients and healthy individuals.ConclusionOur MR results show a causal relationship between the GM and liver disease. Prevotella displays a notable protective effect. This finding may enhance the precision of GM-based therapies and offer new insights for clinical research.
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spelling doaj-art-1c6f7441b83046598ae9e14d55c56d6c2024-11-11T06:10:40ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-11-011510.3389/fgene.2024.13621391362139Causal impact of gut microbiota on five liver diseases: insights from mendelian randomization and single-cell RNA sequencingNa Li0Na Li1Xuanyi Chen2Shuai Xiong3Shuai Xiong4Yuxin Cheng5Jiali Deng6Jiali Deng7Junli Zhang8Fei Yu9Fei Yu10Liyuan Hao11Liyuan Hao12Shenghao Li13Shenghao Li14Xiaoyu Hu15Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaAcupunctureand Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Ophthalmology, Key Laboratory of Sichuan Province Ophthalmopathy Prevention and Cure and Visual Function Protection with TCM, Chengdu, Sichuan, ChinaDepartment of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Infectious Diseases, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaBackgroundLiver disease is among the top ten causes of death globally. With studies suggesting a link between gut microbiota (GM) and liver disease.MethodWe selected summary statistics data from the largest available whole-genome association study (n = 13,266) of GM by the MiBioGen consortium as the exposure, and obtained liver disease-related data from IEU Open GWAS and The NHGRI-EBI GWAS Catalog. A two-sample Mendelian Randomization (MR) analysis employing various methods, to establish the causal relationship between GM and five liver diseases. Meanwhile, single-cell RNA sequencing data were used to examine Prevotella-related genes expression under healthy and disease liver.ResultsThe IVW analysis indicate a causal relationship between GM and liver diseases, with Prevotella exhibiting a protective effect in all five liver diseases: Alcoholic liver disease (OR:0.81,95% confidence interval:0.66-1.00,PIVW = 0.0494); Cirrhosis (OR: 0.85,95% confidence interval: 0.73-0.99,PIVW = 0.0397); Hepatic failure, not elsewhere classified (OR:0.60,95% confidence interval:0.37-0.95,PIVW = 0.0305); Benign neoplasm:Liver (OR:0.39,95% confidence interval:0.2-0.75,PIVW = 0.0046); Malignant neoplasm of liver, primary (OR:0.41, 95% confidence interval:0.18-0.93,PIVW = 0.0334). The single-cell results suggest differential expression of Prevotella-related genes between liver disease patients and healthy individuals.ConclusionOur MR results show a causal relationship between the GM and liver disease. Prevotella displays a notable protective effect. This finding may enhance the precision of GM-based therapies and offer new insights for clinical research.https://www.frontiersin.org/articles/10.3389/fgene.2024.1362139/fullgut microbiotafive liver diseasesPrevotellaMendelian randomizationSNPs
spellingShingle Na Li
Na Li
Xuanyi Chen
Shuai Xiong
Shuai Xiong
Yuxin Cheng
Jiali Deng
Jiali Deng
Junli Zhang
Fei Yu
Fei Yu
Liyuan Hao
Liyuan Hao
Shenghao Li
Shenghao Li
Xiaoyu Hu
Causal impact of gut microbiota on five liver diseases: insights from mendelian randomization and single-cell RNA sequencing
Frontiers in Genetics
gut microbiota
five liver diseases
Prevotella
Mendelian randomization
SNPs
title Causal impact of gut microbiota on five liver diseases: insights from mendelian randomization and single-cell RNA sequencing
title_full Causal impact of gut microbiota on five liver diseases: insights from mendelian randomization and single-cell RNA sequencing
title_fullStr Causal impact of gut microbiota on five liver diseases: insights from mendelian randomization and single-cell RNA sequencing
title_full_unstemmed Causal impact of gut microbiota on five liver diseases: insights from mendelian randomization and single-cell RNA sequencing
title_short Causal impact of gut microbiota on five liver diseases: insights from mendelian randomization and single-cell RNA sequencing
title_sort causal impact of gut microbiota on five liver diseases insights from mendelian randomization and single cell rna sequencing
topic gut microbiota
five liver diseases
Prevotella
Mendelian randomization
SNPs
url https://www.frontiersin.org/articles/10.3389/fgene.2024.1362139/full
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