<b>Gut microbiota and thyroid diseases: a Mendelian randomization study</b>

Background Recent research indicates a potential association between gut flora and thyroid disease. Yet, the precise nature and direction of this hypothetical causal relationship remain elusive. This study aims to explore the potential causal association between gut microorganisms (GM) and various thyroid conditions, including Nontoxic goitre (NTG), Nontoxic multinodular goitre (NTMG), Thyrotoxicosis with toxic multinodular goitre (TTMG), and Thyroid Cancer (THCA). Methods Genome-wide association study (GWAS) statistics were pooled from MiBioGen and FinnGen for the assessment of gut flora and NTG/NTMG/TTMG/THCA. Various statistical methods including Inverse-Variance Weighting (IVW), MR-Egger regression, Weighted Median, Weighted Mode, Simple Mode, cML-MA, and MR-PRESSO were employed to assess the causal relationship between intestinal flora and NTG/NTMG/TTMG/THCA. Reverse Mendelian randomization (MR) analyses were conducted for intestinal flora identified as causally associated with NTG/NTMG/TTMG/THCA in the forward MR analysis. Furthermore, additional MR analysis was conducted after controlling for common confounders. Results Inverse-Variance Weighting revealed that the Rikenellaceae RC9 gut group (OR=1.144, 95% CI: 1.061–1.234, P&lt;0.001, PFDR=0.095) posed a risk for NTG, while Bifidobacterium (OR=0.747, 95% CI: 0.635–0.878, P&lt;0.001, PFDR=0.075) exhibited a protective effect for NTMG. Additionally, Dorea (OR=2.070, 95% CI: 1.343–3.912, P&lt;0.001, PFDR=0.095) and Phascolarctobacterium (OR=2.287, 95% CI: 1.581–3.308, P&lt;0.001, PFDR=0.002) were identified as risk factors for TTMG, while Family XI (OR=0.711, 95% CI: 0.588–0.859, P&lt;0.001, PFDR=0.078) was protective against THCA. Reverse MR analysis showed no significant causal effect of NTG/NTMG/TTMG/THCA on gut microbiota, and no notable heterogeneity or horizontal pleiotropy of instrumental variables was detected. Conclusions This two-sample Mendelian randomization study identified causal associations between Rikenellaceae RC9 gut group, Bifidobacterium, Dorea, Phascolarctobacterium, and Family XI, and NTG/NTMG/TTMG/THCA. Further randomized controlled trials are warranted to clarify the impact of intestinal flora on thyroid disease and its underlying mechanisms.