Fine particulate matter (PM_2.5), a ubiquitous environmental pollutant, has been indicated to affect thyroid hormone (TH) homeostasis in women, but the detailed mechanism behind this effect remains unclear. The objective of this study was to evaluate the roles of the hypothalamic-pituitary-thyroid (HPT) axis and hepatic transthyretin in the thyroid-disrupting effects of PM_2.5. Sprague Dawley rats were treated with PM_2.5 (0, 15 and 30 mg/kg) by passive pulmonary inhalation for 49 days; and recovery experimental group rats were dosed with PM_2.5 (30 mg/kg) for 35 days, and no treatment was done during the subsequent 14 days. PM_2.5 was handled twice a day by passive pulmonary inhalation throughout the study. After treatment, pathological changes were analyzed by performing haemotoxylin and eosin staining, measuring levels of THs and urine iodine (UI) in serum, plasma, and urine samples using enzyme-linked immunoabsorbent assay, and expression of proteins in the hypothalamus, pituitary, thyroid, and liver tissues of rats were analyzed by immunohistochemistry and Western blotting. The levels of oxidative stress factors, such as reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and nuclear factor-kappa B (NF-κB) in female rats' plasma were also evaluated by ELISA. The results of these analyses revealed that PM_2.5 treatment induced pathologic changes in rat thyroid and liver characterized by increased follicular cavity size and decreased amounts of follicular epithelial cells and fat vacuoles, respectively. Serum levels of triiodothyronine, thyroxine, and thyroid stimulating hormone were significantly decreased, plasma NF-κB level was increased and plasma redox state was unbalanced (enhanced ROS, MDA and Gpx levels; reduced SOD activities) in female rats treated with PM_2.5 (P < 0.05). PM_2.5 treatment suppressed the biosynthesis and biotransformation of THs by increasing sodium iodide symporter, thyroid transcription factor 1, thyroid transcription factor 2, and paired box 8 protein expression levels (P < 0.05). Additionally, thyroid stimulating hormone receptor and thyroid peroxidase levels were significantly decreased (P < 0.05). Both thyrotropin releasing hormone receptor and thyroid stimulating hormone beta levels were enhanced (P < 0.05). Moreover, transport of THs was inhibited due to reduced protein expression of hepatic transthyretin upon treatment with PM_2.5. In summary, PM_2.5 treatment could perturb TH homeostasis by affecting TH biosynthesis, biotransformation, and transport, affecting TH receptor levels, and inducing oxidative stress and inflammatory responses. Activation of the HPT axis and altered hepatic transthyretin levels therefore appear to play a crucial role in PM_2.5-induced thyroid dysfunction.

The immune system of some genetically susceptible children can be triggered by certain environmental factors to produce islet autoantibodies (IA) against pancreatic β cells, which greatly increases their risk for Type-1 diabetes. An environmental factor under active investigation is the gut microbiome due to its important role in immune system education. Here, we study gut metagenomes that arede-novo-assembled in 887 at-risk children in the Environmental Determinants of Diabetes in the Young (TEDDY) project. Our results reveal a small set of core protein families, present in >50% of the subjects, which account for 64% of the sequencing reads. Time-series binning generates 21,536 high-quality metagenome-assembled genomes (MAGs) from 883 species, including 176 species that hitherto have no MAG representation in previous comprehensive human microbiome surveys. IA seroconversion is positively associated with 2373 MAGs and negatively with 1549 MAGs. Comparative genomics analysis identifies lipopolysaccharides biosynthesis inBacteroidesMAGs and sulfate reduction inAnaerostipesMAGs as functional signatures of MAGs with positive IA-association. The functional signatures in the MAGs with negative IA-association include carbohydrate degradation in lactic acid bacteria MAGs and nitrate reduction inEscherichiaMAGs. Overall, our results show a distinct set of gut microorganisms associated with IA seroconversion and uncovered the functional genomics signatures of these IA-associated microorganisms

Methylmercury (MeHg), a potent neurotoxic substance, causes adverse health outcomes by modulating metabolites through altered gut microbiota patterns. Among the many metabolites, neurotransmitters play a particularly important role in the nervous system and behavior. Resveratrol (RSV) has been investigated as an antiaging, antioxidant, anti‐inflammatory, and neuroprotective agent. The current study evaluated that RSV is protective of neurodevelopmental toxicity induced by MeHg and further explored the underlying mechanisms. Sprague–Dawley rats were treated with 1.2 mg/kg/d of MeHg, and the effects were evaluated after supplementation with RSV (20 mg/kg/d). The results indicated that MeHg had adverse effects on early neurodevelopmental indicators in the experimental group offspring as compared to control pups. Interestingly, RSV significantly improved the MeHg‐induced delays in the neurobehavioral reflexes and reduced the total mercury (THg) concentration in the colons of the offspring rats. In agreement, RSV administration improved the gut microbiota diversity and structure by increasing the abundance of probiotics and upregulating the expression of tight junction proteins. It also ameliorated the MeHg‐induced abnormalities in the expression profiles of neurotransmitters. Furthermore, eight key bacteria that were strongly linked with the neurotransmitters and neuroreflex parameters were identified. Taken together, these results demonstrate that RSV treatment effectively reduces the occurrence of neurodevelopmental toxicity caused by perinatal MeHg exposure by modulating the intestinal flora and neurotransmitter metabolism. These findings provide a new therapeutic approach for treating MeHg‐induced neurotoxicity.The cover image is based on the Research Article Resveratrol alleviates perinatal methylmercury‐induced neurobehavioral impairments by modulating the gut microbiota composition and neurotransmitter disturbances by Fang Chen et al., https://doi.org/10.1002/tox.23973.