Microplastics and Nanoplastics Cause Thyroid Dysfunction in Adolescent Mice through the Intestinal Microbiota-Mediated Hypothalamus-Pituitary-Thyroid Axis

Polypropylene (PP) and poly-(ethylene terephthalate) (PET) plastic products are widely used in diet packaging and may generate microplastics (MPs) and nanoplastics (NPs) during use. However, their effects and mechanisms on causing endocrine system diseases remain unclear. Here, we established a dietary exposure mouse model using micro and nanoplastics (MNPs) and found that MNPs caused a decrease in thyroid function in adolescent mice. Fecal microbiota transplantation (FMT) was used to reconstruct the intestinal microbiota of mice to reveal the mechanisms of thyroid dysfunction. The abundance of <i>Bacteroides</i> in the intestinal tract significantly changed after FMT. PP-MPs and NPs affected the levels of lysophosphatidylethanolamine and fatty acid esters of hydroxy fatty acids, respectively, which competitively bound to thyrotropin receptor (TSHR) on the thyroid gland, thus affecting the thyroid function. PET-MNPs affected the level of 4-hydroxy-3-methoxyphenylglycol sulfate, which regulated the activity of sympathetic nervous system by acting on the thyrotropin-releasing hormone receptor and TSHR in mice, thereby interfering with the regulatory function of the hypothalamus-pituitary-thyroid (HPT) axis on the synthesis and secretion of thyroid hormones. This study emphasizes the key role of intestinal microbiota-mediated HPT axis in thyroid dysfunction caused by MNP exposure and provides theoretical basis for the prevention of endocrine-related diseases during adolescence caused by MNPs.