Evaluating the reparative effects and the mechanism of action of docosahexaenoic acid on azithromycin-induced lipid metabolism dysfunction

To explore the reparative effects of DHA on the gut microbiome disturbance and dysfunctional lipid metabolism caused by long-term antibiotic therapy, it was tested on an azithromycin (AZI) mouse antibiotic model. Thirty specific-pathogen-free BALB/c mice (SPF grade, half male and half female) were randomly separated into three groups (n = 10, 5 male and 5 female): control group (CK), azithromycin natural recovery group (AZI) and DHA group (DHA). High-throughput sequencing and bioinformatics methods were used to analyze the gut microbiome. ELASE kits were used to measure blood lipid, lipids in the liver, and bile salt hydrolase (BSH) levels in feces. Gas chromatography and UPLC-MS/MS were employed to detect DHA and bile acids contents in liver, respectively. Real-time polymerase chain reaction (RT-PCR) was used to measure the expression of key enzymes involved in lipid metabolism. Long-term AZI treatment led to dyslipidemia, gut microbiome disturbance and anxious behaviors in the mouse model. DHA was found to significantly improve the dyslipidemia and anxiety-like behaviors induced by AZI. DHA had no effect on the structure of gut microbiome and bile acids contents but increased the content of the metabolic enzyme BSH in gut microbiota and normalized the expression of enzymes involved in lipid metabolism.