Impact of gut microbiota on metabolic syndrome and its comprising traits: a two-sample mendelian randomization study

Abstract Background The prevalence of metabolic syndrome is on the rise globally. Understanding the etiology and discovering potential treatment target have become a priority. Observational data have linked gut microbiota with metabolic syndrome and its comprising traits. However, whether these rela...

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Main Authors: Yaodong Zhang, Jinhai Fan
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Diabetology & Metabolic Syndrome
Subjects:
Online Access:https://doi.org/10.1186/s13098-024-01520-8
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author Yaodong Zhang
Jinhai Fan
author_facet Yaodong Zhang
Jinhai Fan
author_sort Yaodong Zhang
collection DOAJ
description Abstract Background The prevalence of metabolic syndrome is on the rise globally. Understanding the etiology and discovering potential treatment target have become a priority. Observational data have linked gut microbiota with metabolic syndrome and its comprising traits. However, whether these relations underlie causal effects remains unclear. Methods Using Inver Variance Weighted (IVW) as primary analysis method, we performed two-sample Mendelian Randomization (MR) analyses to explore the causal relationship between gut microbiota and metabolic syndrome with its comprising traits. Methods including MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Weighted Mode, and Weighted Median were chosen for additional MR analysis to test the robustness of MR results. Cochran’s IVW Q test and leave-one-out IVW analysis tested the heterogeneity among instrumental variables (IVs). Steiger filtering was utilized to exclude all IVs with reverse causality. Genome-wide association study (GWAS) data used in this study were all from the largest respective GWAS studies available. Results Out of 1172 tests, a total of 16 associations with evidence of causality were identified after sensitivity analyses, but only 3 remained after multiple testing correction. Class Melainabacteria (β = 0.02, adjusted P = 0.01) with affiliated order Gastranaerophilales (β = 0.02, adjusted P = 1.20*10− 3) and genus Eubacterium hallii (β = 0.03, adjusted P = 0.03) showed a positive effect on abdominal obesity. All effect sizes were small (abs(β) < 0.1). All causal relationships identified were unidirectional. Conclusions Given the study’s limitations, we found little evidence supporting a large causal effect, i.e. absolute effect size > 0.1, of gut microbial taxa abundance on metabolic syndrome and its comprising traits. This study also suggests that previously reported associations between gut microbiota and metabolic syndrome with its comprising traits may not necessarily lead to causal relations. Clinical trial number Not applicable.
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spelling doaj-art-274feeceaff047c3882f1642bb8ad27f2025-08-20T02:22:30ZengBMCDiabetology & Metabolic Syndrome1758-59962024-11-0116111010.1186/s13098-024-01520-8Impact of gut microbiota on metabolic syndrome and its comprising traits: a two-sample mendelian randomization studyYaodong Zhang0Jinhai Fan1Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Urology, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background The prevalence of metabolic syndrome is on the rise globally. Understanding the etiology and discovering potential treatment target have become a priority. Observational data have linked gut microbiota with metabolic syndrome and its comprising traits. However, whether these relations underlie causal effects remains unclear. Methods Using Inver Variance Weighted (IVW) as primary analysis method, we performed two-sample Mendelian Randomization (MR) analyses to explore the causal relationship between gut microbiota and metabolic syndrome with its comprising traits. Methods including MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Weighted Mode, and Weighted Median were chosen for additional MR analysis to test the robustness of MR results. Cochran’s IVW Q test and leave-one-out IVW analysis tested the heterogeneity among instrumental variables (IVs). Steiger filtering was utilized to exclude all IVs with reverse causality. Genome-wide association study (GWAS) data used in this study were all from the largest respective GWAS studies available. Results Out of 1172 tests, a total of 16 associations with evidence of causality were identified after sensitivity analyses, but only 3 remained after multiple testing correction. Class Melainabacteria (β = 0.02, adjusted P = 0.01) with affiliated order Gastranaerophilales (β = 0.02, adjusted P = 1.20*10− 3) and genus Eubacterium hallii (β = 0.03, adjusted P = 0.03) showed a positive effect on abdominal obesity. All effect sizes were small (abs(β) < 0.1). All causal relationships identified were unidirectional. Conclusions Given the study’s limitations, we found little evidence supporting a large causal effect, i.e. absolute effect size > 0.1, of gut microbial taxa abundance on metabolic syndrome and its comprising traits. This study also suggests that previously reported associations between gut microbiota and metabolic syndrome with its comprising traits may not necessarily lead to causal relations. Clinical trial number Not applicable.https://doi.org/10.1186/s13098-024-01520-8Gut microbiotaMetabolic syndromeMendelian randomizationCausal effectGenetic association
spellingShingle Yaodong Zhang
Jinhai Fan
Impact of gut microbiota on metabolic syndrome and its comprising traits: a two-sample mendelian randomization study
Diabetology & Metabolic Syndrome
Gut microbiota
Metabolic syndrome
Mendelian randomization
Causal effect
Genetic association
title Impact of gut microbiota on metabolic syndrome and its comprising traits: a two-sample mendelian randomization study
title_full Impact of gut microbiota on metabolic syndrome and its comprising traits: a two-sample mendelian randomization study
title_fullStr Impact of gut microbiota on metabolic syndrome and its comprising traits: a two-sample mendelian randomization study
title_full_unstemmed Impact of gut microbiota on metabolic syndrome and its comprising traits: a two-sample mendelian randomization study
title_short Impact of gut microbiota on metabolic syndrome and its comprising traits: a two-sample mendelian randomization study
title_sort impact of gut microbiota on metabolic syndrome and its comprising traits a two sample mendelian randomization study
topic Gut microbiota
Metabolic syndrome
Mendelian randomization
Causal effect
Genetic association
url https://doi.org/10.1186/s13098-024-01520-8
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