A cause–effect relationship between Graves’ disease and the gut microbiome contributes to the thyroid–gut axis: A bidirectional two-sample Mendelian randomization study

Cao, Jun; Wang, Nuo; Luo, Yanyan; Ma, Chao; Chen, Zhuo-Kun; Chenzhao, Changci; Zhang, Feng; Qi, Xin; Wang, Xiong

doi:10.3389/fimmu.2023.977587

Cited by 32 publications

(34 citation statements)

References 48 publications

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“…Individuals with type 2 diabetes exhibit a decreased abundance of Anaerostipes in their gut compared to those in good health ( 63 ). A focused inquiry was conducted to explore the association between the gut microbiota and Graves’ disease (GD), uncovering that Anaerostipes was identified as a safeguarding element ( 64 ). Furthermore, Jiang’s study validated that individuals with GD exhibited reduced quantities of Anaerostipes in their gut microbiota in comparison to the control cohort ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

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

Shi,

Chen,

et al. 2024

Front. Nutr.

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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.

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Section: Discussionmentioning

confidence: 99%

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

Shi,

Chen,

et al. 2024

Front. Nutr.

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“…Therefore, smoking cessation is crucial for managing both diseases. Recently, role of gut microbiota in the pathogenesis of these diseases has been revealed [53][54][55]. Variations in gut microbiota among individuals may impact the pharmacokinetics of anti-rheumatic drugs, resulting in divergent treatment outcomes at an individual level [56].…”

Section: Discussionmentioning

confidence: 99%

Graves’ disease and the risk of immune-mediated diseases: Mendelian randomization and colocalization analyses in East Asian population.

Su,

Gan,

et al. 2023

Preprint

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Background Epidemiological studies have indicated a frequent co-occurrence of Graves' disease (GD) with other immune-mediated diseases (IMDs). However, the causal relationship between them remains uncertain. Objective This study aimed to establish a causal relationship between GD and IMDs, as well as investigate the genetic foundation of comorbidities. Methods We employed Mendelian randomization (MR) to infer a causal relationship between GD and eight IMDs in the East Asian population, namely, systemic lupus erythematosus (SLE), ulcerative colitis (UC), rheumatoid arthritis (RA), atopic dermatitis (AD), Crohn's disease (CD), type 1 diabetes mellitus (T1DM), amyotrophic lateral sclerosis (ALS), and asthma. The causal association was examined using several MR methods. A sensitivity analysis was performed to identify potential heterogeneity and pleiotropy. Finally, we performed colocalization analyses to explore the possible genetic foundation. Results Bidirectional MR analysis indicated that GD increased the risk of SLE (odds ratio [OR]: 1.31, 95% Confidence Interval [CI]: 1.15 to 1.49, P < 0.001) and CD (OR: 1.32, 95%CI: 1.14 to 1.52, P < 0.001), and maybe a risk factor for RA, but a protective factor for AD and asthma. And we found that RA was linked to a higher risk of GD (OR: 1.26, 95%CI: 1.09 to 1.46, P = 0.002). UC and AD may be protective factors for GD, while CD was the opposite. Colocalization analyses suggested that shared causal variants between GD and other IMDs may exist. Conclusion This study has confirmed that GD was associated with IMDs. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.

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“…This implies that upon removal of each SNP, overall error lines remain relatively stable (all error lines either predominantly on the right or left side of 0), indicating reliable outcomes. All methof above use the TwoSampleMR package 46 in R software (4.2.3; The R Foundation for Statistical Computing, Vienna, Austria).…”

Section: Methodsmentioning

confidence: 99%

Causal relationship between gut microbiome and sex hormone‐binding globulin: A bidirectional two‐sample Mendelian randomization study

Yan,

Zheng,

Xia

et al. 2024

American J Rep Immunol

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ProblemCurrently, there is a variety of evidence linking the gut microbiota to changes in sex hormones. In contrast, the causal relationship between SHBG, a carrier of sex hormones, and the gut microbiota is unclear.Method of StudyBidirectional two‐sample Mendelian randomization (MR) analysis was used to detect the causal effect between SHBG and the gut microbiome. Summary statistics of genome‐wide association studies (GWASs) for the gut microbiome and SHBG were obtained from public datasets. Inverse‐variance weighting (IVW), weighted median, weighted mode, MR‐Egger and simple mode methods were used to operate the MR analysis. F‐statistics and sensitivity analyses performed to evaluate bias and reliability.ResultsWhen we set gut microbiome as exposure and SHBG as outcome, we identified nine causal relationships. In males, Coprobacter (PIVW = 2.01 × 10−6), Ruminococcus2 (PIVW = 3.40 × 10−5), Barnesiella (PIVW = 2.79 × 10−2), Actinobacteria (PIVW = 3.25 × 10−2) and Eubacterium fissicatena groups (PIVW = 3.64 × 10−2) were associated with lower SHBG levels; Alphaproteobacteria (PIVW = 1.61 × 10−2) is associated with higher SHBG levels. In females, Lachnoclostridium (PIVW = 9.75 × 10−3) and Defluviitaleaceae UCG011 (PIVW = 3.67 × 10−2) were associated with higher SHBG levels; Victivallaceae (PIVW = 2.23 × 10−2) was associated with lower SHBG levels. According to the results of reverse MR analysis, three significant causal effect of SHBG was found on gut microbiota. In males, Dorea (PIVW = 4.17 × 10−2) and Clostridiales (PIVW = 4.36 × 10−2) were associated with higher SHBG levels. In females, Lachnoclostridium (PIVW = 7.44 × 10−4) was associated with higherr SHBG levels. No signifcant heterogeneity of instrumental variables or horizontal pleiotropy was found in bidirectional two‐sample MR analysis.ConclusionsThis study may provide new insights into the causal relationship between the gut microbiome and sex hormone‐binding protein levels, as well as new treatment and prevention strategies for diseases such as abnormal changes in sex hormones.

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A cause–effect relationship between Graves’ disease and the gut microbiome contributes to the thyroid–gut axis: A bidirectional two-sample Mendelian randomization study

Cited by 32 publications

References 48 publications

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

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

Graves’ disease and the risk of immune-mediated diseases: Mendelian randomization and colocalization analyses in East Asian population.

Causal relationship between gut microbiome and sex hormone‐binding globulin: A bidirectional two‐sample Mendelian randomization study

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