Alterations in the gut microbiota and its metabolic profile of PM_2.5 exposure-induced thyroid dysfunction rats

Fine particulate matter (PM_2.5) has drawn more and more interest due to its adverse effects on health. Thyroid has been demonstrated to be the key organ impacted by PM_2.5. However, the mechanisms for PM_2.5 exposure-induced thyrotoxicity remain unclear. To explore the mechanisms, a rat thyroid injury model was established by exposing rats to PM_2.5 via passive pulmonary inhalation. Thyroid hormones and thyroid function proteins were detected. The thyroid function affected by PM_2.5 exposure was investigated via metabolomics analysis using liquid chromatography-mass spectrometry and 16S rRNA gene sequencing. Results showed that PM_2.5 exposure induced remarkable alterations in gut microbiome evenness, richness, and composition. Metabolomics profiling revealed that the urine metabolites levels were changed by PM_2.5 exposure. The altered gut microbiota and urine metabolites showed significant correlations with thyroid function indicators (total T3, total T4 and thyrotropin hormone, etc.). These metabolites were involved in metabolic pathways including thyroid hormone synthesis, metabolisms of tryptophan, d-Glutamine and D-glutamate, histidine, glutathione, etc. The altered gut microbiota showed significant correlations with urine metabolites (glutathione, citric acid, D-Glutamic acid, kynurenic acid and 5-Aminopentanoic acid, etc.). For example, the taurocholic acid levels positively correlated with the relative abundance of several genera including Elusimicrobium (r = 0.9741, p = 0.000000), Muribaculum (r = 0.9886, p = 0.000000), Candidatus_Obscuribacter (r = 0.8423, p = 0.000585), Eubacterium (r = 0.9237, p = 0.000017), and Parabacteroides (r = 0.8813, p = 0.000150), while it negatively correlated with the relative abundance of Prevotella (r = -0.8070, p = 0.001509). PM_2.5 exposure-induced thyrotoxicity led to remarkable alterations both in gut microbiome composition and some metabolites involved in metabolic pathways. The altered intestinal flora and metabolites can in turn influence thyroid function in rats. These findings may provide novel insights regarding perturbations of the gut-thyroid axis as a new mechanism for PM_2.5 exposure-induced thyrotoxicity.