Reshaping commensal gut microbiota in early life with amoxicillin presents with lower blood pressure

Pediatric hypertension is recognized as an emerging global health concern. While new guidelines are developed for facilitating clinical management, the reasons for the prevalence of hypertension in children remain unknown. Genetics and environmental factors do not fully account for the growing incidence of pediatric hypertension. Because stable bacterial flora in early life are linked with health outcomes later in life, we hypothesized that reshaping of gut microbiota in early developmental stages of life affects blood pressure (BP) of pediatric subjects. To test this hypothesis, we administered amoxicillin, the most commonly prescribed pediatric antibiotic, to alter gut microbiota of young, genetically hypertensive rats (study 1) and dams during gestation and lactation to reshape microbiota of offspring (study 2). Reshaping of microbiota, with reductions in Firmicutes/Bacteriodetes ratio observed in Amoxicillin treated young rats and in dams. Amoxicillin treated rats also had lower blood pressure compared to the untreated rats. In the young rats treated with amoxicillin, the lowering effect on blood pressure persisted even after the antibiotics were discontinued. Similarly, the offspring from the dams treated with amoxicillin also showed lower systolic blood pressure compared to the control rats. Remarkably, in all cases, a decrease in BP was associated with lowering of Veillonellaceae, which are succinate-producing bacteria. Elevated plasma succinate is reported in hypertension. Accordingly, serum succinate was measured and found lower in animals treated with amoxicillin. Our results demonstrate a direct correlation between succinate-producing gut microbiota and early development of hypertension, and indicate that reshaping gut microbiota, especially by depleting succinate-producing microbiota early in life may have long-term benefits for hypertension-prone individuals