Relationship between gut microbiota and thyroid function: a two-sample Mendelian randomization study

BackgroundNumerous observational studies have indicated a link between the composition of gut microbiota and thyroid function. Nevertheless, the precise causal relationship between gut microbiota and thyroid function remains uncertain.MethodsIn this two-sample Mendelian randomization study, we utili...

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Main Authors: Liangzhuo Xie, Huaye Zhao, Wei Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-09-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1240752/full
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author Liangzhuo Xie
Huaye Zhao
Wei Chen
Wei Chen
author_facet Liangzhuo Xie
Huaye Zhao
Wei Chen
Wei Chen
author_sort Liangzhuo Xie
collection DOAJ
description BackgroundNumerous observational studies have indicated a link between the composition of gut microbiota and thyroid function. Nevertheless, the precise causal relationship between gut microbiota and thyroid function remains uncertain.MethodsIn this two-sample Mendelian randomization study, we utilized summary data from a genome-wide association study of gut microbiota composition in 18,340 participants from 24 cohorts, as well as summary statistics on thyroid hormones and thyroid-stimulating hormone from the ThyroidOmics Consortium and summary statistics on hypothyroidism and hyperthyroidism from the FinnGen R8 release. Five different methods, including inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode, were employed to examine the causal relationship between gut microbiota and thyroid function. Reverse Mendelian randomization analysis was conducted for taxa identified as having a causal relationship with thyroid function in the Mendelian randomization analysis. To assess the robustness of the results, sensitivity analyses were conducted employing Cochran’s Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis.ResultsThrough MR analysis of 211 microbial taxa and 4 phenotypes, we identified a total of 34 gut microbiota taxa that were associated with the outcomes. After using the bonferroni method for multiple testing correction, phylum Actinobacteria (id.400) had a protective effect on hypothyroidism (OR=0.883, 95% CI: 0.817-0.955, P=0.002), and class Deltaproteobacteria (id.3087) had a protective effect on hyperthyroidism (OR=0.549, 95% CI: 0.374-0.805, P=0.002). According to the results of reverse MR analysis, no significant causal effect of the four phenotypes was found on gut microbiota. No significant horizontal pleiotropy was detected based on MR-Egger intercept test and MR-PRESSO global test.ConclusionThrough two-sample MR analysis, we identified specific gut microbiota taxa at the genetic level that are predicted to have a causal relationship with thyroid function, which may serve as useful biomarkers for early disease diagnosis.
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spelling doaj.art-511bd1f4a06b4de0adb5697e6d2c80252023-09-27T10:53:08ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-09-011410.3389/fendo.2023.12407521240752Relationship between gut microbiota and thyroid function: a two-sample Mendelian randomization studyLiangzhuo Xie0Huaye Zhao1Wei Chen2Wei Chen3Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, ChinaSchool of Tranditional Chinese, Liaoning University of Traditional Chinese Medicine, Shenyang, ChinaGraduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, ChinaDepartment of Geriatrics, The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, ChinaBackgroundNumerous observational studies have indicated a link between the composition of gut microbiota and thyroid function. Nevertheless, the precise causal relationship between gut microbiota and thyroid function remains uncertain.MethodsIn this two-sample Mendelian randomization study, we utilized summary data from a genome-wide association study of gut microbiota composition in 18,340 participants from 24 cohorts, as well as summary statistics on thyroid hormones and thyroid-stimulating hormone from the ThyroidOmics Consortium and summary statistics on hypothyroidism and hyperthyroidism from the FinnGen R8 release. Five different methods, including inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode, were employed to examine the causal relationship between gut microbiota and thyroid function. Reverse Mendelian randomization analysis was conducted for taxa identified as having a causal relationship with thyroid function in the Mendelian randomization analysis. To assess the robustness of the results, sensitivity analyses were conducted employing Cochran’s Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis.ResultsThrough MR analysis of 211 microbial taxa and 4 phenotypes, we identified a total of 34 gut microbiota taxa that were associated with the outcomes. After using the bonferroni method for multiple testing correction, phylum Actinobacteria (id.400) had a protective effect on hypothyroidism (OR=0.883, 95% CI: 0.817-0.955, P=0.002), and class Deltaproteobacteria (id.3087) had a protective effect on hyperthyroidism (OR=0.549, 95% CI: 0.374-0.805, P=0.002). According to the results of reverse MR analysis, no significant causal effect of the four phenotypes was found on gut microbiota. No significant horizontal pleiotropy was detected based on MR-Egger intercept test and MR-PRESSO global test.ConclusionThrough two-sample MR analysis, we identified specific gut microbiota taxa at the genetic level that are predicted to have a causal relationship with thyroid function, which may serve as useful biomarkers for early disease diagnosis.https://www.frontiersin.org/articles/10.3389/fendo.2023.1240752/fullgut microbiotathyroid functioncausal effecthypothyroidismhyperthyroidismMendelian randomization
spellingShingle Liangzhuo Xie
Huaye Zhao
Wei Chen
Wei Chen
Relationship between gut microbiota and thyroid function: a two-sample Mendelian randomization study
Frontiers in Endocrinology
gut microbiota
thyroid function
causal effect
hypothyroidism
hyperthyroidism
Mendelian randomization
title Relationship between gut microbiota and thyroid function: a two-sample Mendelian randomization study
title_full Relationship between gut microbiota and thyroid function: a two-sample Mendelian randomization study
title_fullStr Relationship between gut microbiota and thyroid function: a two-sample Mendelian randomization study
title_full_unstemmed Relationship between gut microbiota and thyroid function: a two-sample Mendelian randomization study
title_short Relationship between gut microbiota and thyroid function: a two-sample Mendelian randomization study
title_sort relationship between gut microbiota and thyroid function a two sample mendelian randomization study
topic gut microbiota
thyroid function
causal effect
hypothyroidism
hyperthyroidism
Mendelian randomization
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1240752/full
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AT huayezhao relationshipbetweengutmicrobiotaandthyroidfunctionatwosamplemendelianrandomizationstudy
AT weichen relationshipbetweengutmicrobiotaandthyroidfunctionatwosamplemendelianrandomizationstudy
AT weichen relationshipbetweengutmicrobiotaandthyroidfunctionatwosamplemendelianrandomizationstudy