Exposure to oral antibiotics induces gut microbiota dysbiosis associated with lipid metabolism dysfunction and low-grade inflammation in mice

Abstract

Due to a long history of improper and excessive use, Penicillin G (Pen G) and erythromycin (Ery) are regularly detected in environmental samples and pose a great threat to human health. Here, we set out to investigate effects of Pen G, Ery or their mixture on lipid metabolismand gut microbiota in order to better understand their toxicological mechanisms. Male C57BL/6J mice were exposed either to 60 μ g/ml Pen G, Ery or a half mixture of both for 6 weeks or to 10 μ g/ml Pen G, Ery or a half mixture of both for 14 weeks. In a recovery experiment, male mice were exposed to 60 μ g/ml Pen G or Ery for 2 weeks and then maintained without antibiotics for up to 8 weeks. It was observed that oral exposure to Pen G, Ery or their mixture induced lipid metabolismdysfunction, characterized by significantly increased lipid accumulations, triglycerides (TG) levels and expression of key genes involved in free fatty acid (FFA) synthesis, FFA transport and TG synthesis in the liver. In addition, Pen G and Ery exposure induced an inflammatory response as indicated by the increase of serum lipopolysaccharide levels and the up-regulation of key genes that regulate immune responses in the liver, fat, colon and ileum. Moreover, Pen G and Ery exposure rapidly and dramatically altered the composition of the microbiota in feces and cecum. Furthermore, high throughput sequencing of V3-V4 region of bacterial 16S rRNA gene revealed additional significant changes in the cecal microbiota of antibiotics-treated mice. Importantly, it took a very long time to reconstitute the normal composition of the gut microbiota after it was imbalanced by antibiotics exposure. Orally administered Pen G and Ery (especially to the latter) can induce gut microbiota dysbiosis, which may indirectly link antibiotic exposure to host metabolic disorders and inflammation.