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.

The relevance of DHA with modulating of host-gut microbiome signatures alterations and repairing of lipids metabolism shifts.

Huge of previous reports recommended that gut microbiome have a crucial role in the human health and its change was profound impact for the metabolic improvements associated with lipids metabolism. In order to explore the relevance of a direct dysbiosis effect of gut microbiome on lipids metabolism shifts and repaired position of DHA, we built the animal model for the study with gut microbiome dysbiosis administrated by i.g. with CRO and intervened by DHA in the present work. Gut microbiome was analyzed by high throughput sequencing and bioinformatics analyses of bacteria. The composition of fatty acids and short chain fatty acids (SCFAs) were determined by gas chromatography. Blood lipids and bile acids were assayed by kit and UPLC-MS/MS, respectively. The expressions of enzymes of long chain fatty acid metabolism were analyzed by qRT-PCR. The results showed that gut microbiome dysbiosis caused lipid metabolism abnormal, and DHA was able to repair the lipids metabolism shifts resulted from gut microbiome dysbiosis. DHA could modulate host-gut microbiome signatures, improve concentrations of SCFAs, regulate fatty acids metabolism but modify bile acid profiles. In conclusion, we considered that DHA repaired lipid metabolism by modulating gut microbiome and regulating fatty acids metabolism pathway.