Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study

BackgroundMultiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism.MethodsTo investigate the connection between the gut microbiota and hy...

Full description

Bibliographic Details
Main Authors: Chao Shi, Jie Chen, Siying He, Yingying Zhang, Yanyue Zhang, Lisha Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Nutrition
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2024.1286593/full
_version_ 1827315510783508480
author Chao Shi
Jie Chen
Siying He
Yingying Zhang
Yanyue Zhang
Lisha Yu
author_facet Chao Shi
Jie Chen
Siying He
Yingying Zhang
Yanyue Zhang
Lisha Yu
author_sort Chao Shi
collection DOAJ
description BackgroundMultiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism.MethodsTo investigate the connection between the gut microbiota and hypothyroidism, two-sample Mendelian randomization was performed using data from a genome-wide association study meta-analysis (n = 18,430) conducted by the MiBioGen consortium. Summary statistics for hypothyroidism (26,342 cases and 59,827 controls) were obtained using the data from the FinnGen consortium R8 release data. To investigate the causal link between the gut microbiota and hypothyroidism, various methods, including MR-Egger, weighted median, weighted model, simple model, MR-PRESSO, and inverse variance weighted (IVW), were employed. The bacteria that were causally linked to hypothyroidism in forward Mendelian randomization analysis were subjected to reverse Mendelian randomization analysis. Cochran’s Q statistics were utilized to gauge the heterogeneity of the instrumental variables.ResultsThe results indicated that Akkermansia had a positive impact on hypothyroidism, with an odds ratio of 0.84 (95% CI 0.74–0.95, p = 0.01) based on the inverse variance-weighted estimates. Additionally, Anaerostipes (OR = 1.17, 95% CI 1.01–1.36, p = 0.04), Butyrivibrio (OR = 0.93, 95% CI 0.88–0.99, p = 0.02), Holdemania (OR = 0.89, 95% CI 0.81–0.99, p = 0.03), Intestinimonas (OR = 1.13, 95% CI 1.02–1.26, p = 0.03), Ruminiclostridium5 (OR = 1.19, 95% CI 1.01–1.41, p = 0.04), and Ruminococcaceae UCG-011 (OR = 0.91, 95% CI 0.84–0.99, p = 0.03) were identified. The gut microbiota was not significantly affected by hypothyroidism, as indicated by the results of the reverse MR analysis. There was no significant variation in the instrumental variables or horizontal pleiotropy.ConclusionThe findings of this study using two-sample Mendelian randomization indicate a causal relationship between Akkermansia and hypothyroidism. Increased Akkermansia inhibits the onset and progression of hypothyroidism. Additional randomized controlled experiments are necessary to elucidate the beneficial impact of probiotics on hypothyroidism and their distinct protective mechanisms.
first_indexed 2024-04-24T22:56:33Z
format Article
id doaj.art-eef88d35593941c089e43260d3f7d56f
institution Directory Open Access Journal
issn 2296-861X
language English
last_indexed 2024-04-24T22:56:33Z
publishDate 2024-03-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Nutrition
spelling doaj.art-eef88d35593941c089e43260d3f7d56f2024-03-18T04:58:03ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2024-03-011110.3389/fnut.2024.12865931286593Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization studyChao ShiJie ChenSiying HeYingying ZhangYanyue ZhangLisha YuBackgroundMultiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism.MethodsTo investigate the connection between the gut microbiota and hypothyroidism, two-sample Mendelian randomization was performed using data from a genome-wide association study meta-analysis (n = 18,430) conducted by the MiBioGen consortium. Summary statistics for hypothyroidism (26,342 cases and 59,827 controls) were obtained using the data from the FinnGen consortium R8 release data. To investigate the causal link between the gut microbiota and hypothyroidism, various methods, including MR-Egger, weighted median, weighted model, simple model, MR-PRESSO, and inverse variance weighted (IVW), were employed. The bacteria that were causally linked to hypothyroidism in forward Mendelian randomization analysis were subjected to reverse Mendelian randomization analysis. Cochran’s Q statistics were utilized to gauge the heterogeneity of the instrumental variables.ResultsThe results indicated that Akkermansia had a positive impact on hypothyroidism, with an odds ratio of 0.84 (95% CI 0.74–0.95, p = 0.01) based on the inverse variance-weighted estimates. Additionally, Anaerostipes (OR = 1.17, 95% CI 1.01–1.36, p = 0.04), Butyrivibrio (OR = 0.93, 95% CI 0.88–0.99, p = 0.02), Holdemania (OR = 0.89, 95% CI 0.81–0.99, p = 0.03), Intestinimonas (OR = 1.13, 95% CI 1.02–1.26, p = 0.03), Ruminiclostridium5 (OR = 1.19, 95% CI 1.01–1.41, p = 0.04), and Ruminococcaceae UCG-011 (OR = 0.91, 95% CI 0.84–0.99, p = 0.03) were identified. The gut microbiota was not significantly affected by hypothyroidism, as indicated by the results of the reverse MR analysis. There was no significant variation in the instrumental variables or horizontal pleiotropy.ConclusionThe findings of this study using two-sample Mendelian randomization indicate a causal relationship between Akkermansia and hypothyroidism. Increased Akkermansia inhibits the onset and progression of hypothyroidism. Additional randomized controlled experiments are necessary to elucidate the beneficial impact of probiotics on hypothyroidism and their distinct protective mechanisms.https://www.frontiersin.org/articles/10.3389/fnut.2024.1286593/fullhypothyroidismgut microbiomecausal effectMendelian randomizationprobiotics
spellingShingle Chao Shi
Jie Chen
Siying He
Yingying Zhang
Yanyue Zhang
Lisha Yu
Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study
Frontiers in Nutrition
hypothyroidism
gut microbiome
causal effect
Mendelian randomization
probiotics
title Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study
title_full Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study
title_fullStr Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study
title_full_unstemmed Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study
title_short Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study
title_sort cross talk between the gut microbiota and hypothyroidism a bidirectional two sample mendelian randomization study
topic hypothyroidism
gut microbiome
causal effect
Mendelian randomization
probiotics
url https://www.frontiersin.org/articles/10.3389/fnut.2024.1286593/full
work_keys_str_mv AT chaoshi crosstalkbetweenthegutmicrobiotaandhypothyroidismabidirectionaltwosamplemendelianrandomizationstudy
AT jiechen crosstalkbetweenthegutmicrobiotaandhypothyroidismabidirectionaltwosamplemendelianrandomizationstudy
AT siyinghe crosstalkbetweenthegutmicrobiotaandhypothyroidismabidirectionaltwosamplemendelianrandomizationstudy
AT yingyingzhang crosstalkbetweenthegutmicrobiotaandhypothyroidismabidirectionaltwosamplemendelianrandomizationstudy
AT yanyuezhang crosstalkbetweenthegutmicrobiotaandhypothyroidismabidirectionaltwosamplemendelianrandomizationstudy
AT lishayu crosstalkbetweenthegutmicrobiotaandhypothyroidismabidirectionaltwosamplemendelianrandomizationstudy