Causal relationships between gut microbiota and hypothyroidism: a Mendelian randomization study.

Background: Previous studies have shown that the gut microbiota plays an important role in the maintenance of thyroid homeostasis. We aimed to evaluate the causal relationships between gut microbiota and hypothyroidism.

Methods: Summary statistics for 211 gut microbiota taxa were obtained from the largest available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen consortium. Summary statistics for hypothyroidism were obtained from two distinct sources: the FinnGen consortium R9 release data (40,926 cases and 274,069 controls) and the UK Biobank data (22,687 cases and 440,246 controls), respectively. A two-sample Mendelian randomization (MR) design was employed, and thorough sensitivity analyses were carried out to ensure the reliability of the results.

Results: Based on the FinnGen consortium, we found increased levels of Intestinimonas (OR = 1.09; 95%CI = 1.02-1.16; P = 0.01) and Ruminiclostridium5 (OR = 1.11; 95%CI = 1.02-1.22; P = 0.02) may be associated with a higher risk of hypothyroidism, while increased levels of Butyrivibrio (OR = 0.95; 95%CI = 0.92-0.99; P = 0.02), Eggerthella (OR = 0.93; 95%CI = 0.88-0.98; P = 0.01), Lachnospiraceae UCG008 (OR = 0.92; 95%CI = 0.85-0.99; P = 0.02), Ruminococcaceae UCG011 (OR = 0.95; 95%CI = 0.90-0.99; P = 0.02), and Actinobacteria (OR = 0.88; 95%CI = 0.80-0.97; P = 0.01) may be associated with a lower risk. According to the UK Biobank data, Eggerthella and Ruminiclostridium5 remain causally associated with hypothyroidism. The sensitivity analysis demonstrates consistent results without evidence of heterogeneity or pleiotropy.

Conclusion: This study highlights the impact of specific gut microbiota on hypothyroidism. Strategies to change composition of gut microbiota may hold promise as potential interventions.