Cecal microbial transplantation attenuates hyperthyroid-induced thermogenesis in Mongolian gerbils

Endothermic mammals have a high energy cost to maintain a stable and high body temperature (T_b , around 37°C). Thyroid hormones are a major regulator for energy metabolism and T_b . The gut microbiota is involved in modulating host energy metabolism. However, whether the interaction between the gut microbiota and thyroid hormones is involved in metabolic and thermal regulations is unclear. We hypothesized that thyroid hormones via an interaction with gut microbiota orchestrate host thermogenesis and T_b . l-thyroxine-induced hyperthyroid Mongolian gerbils (Meriones unguiculatus) increased resting metabolic rate (RMR) and T_b , whereas Methimazole-induced hypothyroid animals decreased RMR. Both hypothyroid and hyperthyroid animals differed significantly in faecal bacterial community. Hyperthyroidism increased the relative abundance of pathogenic bacteria, such as Helicobacter and Rikenella, and decreased abundance of beneficial bacteria Butyricimonas and Parabacteroides, accompanied by reduced total bile acids and short-chain fatty acids. Furthermore, the hyperthyroid gerbils transplanted with the microbiota from control donors increased type 2 deiodinase (DIO2) expression in the liver and showed a greater rate of decline of both serum T3 and T4 levels and, consequently, a more rapid recovery of normal RMR and T_b . These findings indicate that thyroid hormones regulate thermogenesis depending on gut microbiota and colonization with normal microbiota by caecal microbial transplantation attenuates hyperthyroid-induced thermogenesis. This work reveals the functional consequences of the gut microbiota-thyroid axis in controlling host metabolic physiology and T_b in endotherms.