Enterococcus faecalis contributes to hypertension and renal injury in Sprague-Dawley rats by disturbing lipid metabolism

Abstract

OBJECTIVE: Increasing studies have demonstrated that gut microbiota play vital roles in the development of hypertension. However, the underlying mechanism is not fully understood. METHODS: The relative abundance of Enterococcus faecalis was determined in the faecal samples of angiotensin II or deoxycorticosterone acetate/salt-induced hypertensive rats. Then, E. faecalis culture was administered orally to rats for 6 weeks. Blood pressure (BP) was measured, renal injury was estimated and a serum metabolomic analysis was performed. RESULTS: Compared with control, E. faecalis was markedly enriched in the faecal samples of hypertensive rats. The rats receiving live E. faecalis but not dead bacteria exhibited higher BP and enhanced renal injury. The serum metabolomic data showed that the E. faecalis treatment resulted in 35 variable metabolites including 16 (46%) lipid/lipid-like molecules, suggesting significant disturbance of lipid metabolism. Furthermore, the mRNA levels of 18 lipid metabolic enzymes in the renal medulla and cortex presented distinct and dynamic changes in response to 3 or 6-week E. faecalis treatment. Consistently, the protein levels of lysophospholipases A1 (LYPLA1) and phospholipase A2 group 4 A (PLA2G4) were enhanced only by live E. faecalis, which thus may have decreased the nitric oxide production in the renal medulla and elevated BP. CONCLUSION: Our results suggest that E. faecalis in the gut contributes to hypertension and renal injury in rats by disturbing the lipid metabolism. The information provided here could shed new light on the pathologic mechanisms and potential intervention targets for the treatment of gut dysbiosis-induced hypertension.