Diosbulbin B attenuates propylthiouracil-induced thyroid enlargement in mice by regulating the gut microbiota-short chain fatty acids-thyroid axis.

Abstract

This research investigates Diosbulbin B's capacity to protect against propylthiouracil-induced thyroid enlargement in mice and examines its underlying operative principles. Propylthiouracil was administered to mice by gavage for 15 days to establish a mouse thyroid enlargement model. Meanwhile, Diosbulbin B was administered to the mice as an intervention. After the experiment, biochemical indicators were measured, and, together with non-targeted metabolomics, targeted metabolomics, 16S rDNA sequencing, and Spearman correlation analysis, the alleviating effect of Diosbulbin B on thyromegaly induced by propylthiouracil and its potential mechanism were systematically evaluated. Diosbulbin B decreased thyroid function markers and ameliorated pathological alterations in the thyroid induced by propylthiouracil. Additionally, it alleviated propylthiouracil-induced inflammatory responses and oxidative damage in thyroid tissue. Untargeted metabolomics revealed Diosbulbin B primarily normalized propylthiouracil-disrupted fatty acid metabolism. Crucially, Diosbulbin B reversed the consumption of SCFAs in feces. What is more, 16S rDNA gene sequencing analysis demonstrated that Diosbulbin B successfully rebalanced the gut microbiome by boosting the population of beneficial bacteria while cutting down on harmful microorganisms, effectively bringing the intestinal flora structure back to normal. On top of that, when we looked at the connection between fatty acids and gut bacteria, it became clear that Firmicutes, Bacteroidota, and Verrucomicrobia, along with propionic, butyric, and acetic acids, could be considered key indicators of thyroid enlargement caused by propylthiouracil. Diosbulbin B significantly improved propylthiouracil-induced thyroid enlargement by regulating the intestinal flora, increasing fatty acid production, and reducing inflammation and oxidative stress.