Objectives: Observational research shows associations of the gut microbiota and its metabolites with autoimmune thyroid disease (AITD), but the causality is undetermined. Methods: Two-sample Mendelian randomization (MR) was employed to analyze the association of the gut microbiota and its metabolites with AITD. A total of 119 gut microbiotas and nine fecal/circulating metabolites were the exposures. AITD, Graves’ disease (GD), and Hashimoto’s thyroiditis (HT) were the outcomes. Inverse-variance weighting (IVW) was primarily used to assess causality; Cochran’s Q was used to assess heterogeneity. Sensitivity analyses (weighted median, MRPRESSO regression, MRPRESSO intercept, MRPRESSO global, Steiger filtering, leave-one-out) were conducted to assess causal estimate robustness. Multivariable MR (MVMR) was used to estimate the effects of body mass index (BMI) and alcohol consumption frequency on causality. Results: The outcomes were potentially causally associated with 22 gut microbiotas and three metabolites. After multiple-test correction, 3-indoleglyoxylic acid retained significant causality with AITD (IVW: odds ratio [OR] = 1.09, 95% confidence interval [CI] = 1.05–1.14, p = 2.43 × 10⁻⁵, FDR = 0.009). The sensitivity analyses were confirmatory (weighted median: OR = 1.06, 95% CI = 1.01–1.12, p = 0.025; MRPRESSO: OR = 1.09, 95% CI = 1.15–1.14, p = 0.001). MVMR revealed no confounding effects on this association (BMI: OR = 1.21, 95% CI =1.08–1.35, p = 0.001; drinks/week: OR = 1.22, 95% CI = 1.04–1.43, p = 0.014). Conclusions: MR revealed no significant causal effects of the gut microbiota on the outcomes. However, MR revealed the causal effects of 3-indoleglyoxylic acid on the risk of AITD.

Objectives: The objective of this study was to examine the urinary iodine concentration (UIC)–thyroid autoimmunity (TAI) association and UIC–selenium intake interaction in U.S. adults. Methods: We analyzed 2007–2012 National Health and Nutrition Examination Survey (NHANES) data on ≥20-year-old adults (n = 6612). Their food and supplemental selenium intake was measured. The associations of the UIC and selenium intake with thyroid peroxidase antibody (TPOAb) positivity, thyroglobulin antibody (TgAb) positivity, and TAI were assessed via weighted multivariable logistic regression. Interaction and subgroup analyses were conducted. Nonlinear relationships were explored and visualized via restricted cubic splines (RCSs). Results: Compared with a UIC 100~200 μg/L, a UIC 500~800 μg/L was associated with a 57% increased TPOAb positivity risk (OR = 1.57 [CI = 1.07–2.30]; p = 0.022), a one-fold greater TgAb positivity risk (OR = 2.00 [CI = 1.10–3.65]; p = 0.025), and a 62% increased TAI risk (OR = 1.62 [CI = 1.07–2.45]; p = 0.024). Nonlinear relationships between the UIC and thyroid antibody positivity were observed. According to the univariate models, each 1 μg increase in selenium intake was associated with a 0.049 IU/mL decrease in the TPOAb levels (β [95% CI] = −0.049 [−0.092–−0.005]; p = 0.028). In the low-selenium group, a UIC of 200~300 μg/L was a risk factor for TPOAb positivity (p = 0.046). At a moderate level of selenium intake, a UIC of 300~800 μg/L significantly increased the TPOAb positivity risk (all p < 0.05). At a high level of selenium intake, the UIC and TPOAb positivity risks were not significantly associated (all p > 0.05). Conclusions: A UIC of 500~800 μg/L is an independent TAI risk factor. The selenium intake modifies the UIC–thyroid antibody positivity relationship, with the association disappearing at high selenium levels.