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Area of Science:

  • Endocrinology
  • Microbiome Research
  • Metabolomics

Background:

  • A bidirectional relationship exists between thyroid function and the gut microbiome.
  • Gut microbiome-derived metabolites, including choline, trimethylamine N-oxide (TMAO), and betaine, are increasingly recognized for their systemic effects.
  • Thyroid dysfunction can influence gut microbial composition and function.

Purpose of the Study:

  • To investigate the association between circulating gut microbiome-derived metabolites (choline, TMAO, betaine) and thyroid function status in euthyroid individuals.
  • To explore the relationship between thyroid stimulating hormone (TSH) levels and specific microbial metabolites.
  • To examine potential interactions between these metabolites, thyroid function, and cardiometabolic risk factors like fatty liver.

Main Methods:

  • Analysis of 4771 euthyroid participants from the PREVEND cohort study.
  • Measurement of plasma choline, TMAO, and betaine using nuclear magnetic resonance spectroscopy.
  • Statistical assessment of associations between TSH levels and metabolite concentrations using linear regression, with adjustments for confounders.

Main Results:

  • Plasma choline levels were significantly higher in participants with higher TSH quartiles (p < 0.001).
  • A positive association was observed between choline and TSH in fully adjusted analyses (std β: 0.04, p = 0.012).
  • The association between choline and TSH was stronger in individuals with an elevated fatty liver index (p = 0.003).

Conclusions:

  • Low-normal thyroid function, indicated by higher TSH levels within the reference range, is associated with increased plasma choline.
  • This association may be mediated by gut microbiome-derived metabolites and could influence cardiometabolic health, particularly in individuals with metabolic dysfunction.
  • Further research is warranted to elucidate the causal pathways and clinical implications of these findings for cardiovascular disease risk.