Disparate effects of antibiotics on hypertension.

Abstract

Gut microbiota are associated with a variety of complex polygenic diseases. The usage of broad-spectrum antibiotics by patients affected by such diseases is an important environmental factor to consider, because antibiotics, which are widely prescribed to curb pathological bacterial infections, also indiscriminately eliminate gut commensal microbiota. However, the extent to which antibiotics reshape gut microbiota and per se contribute to these complex diseases is understudied. Because genetics play an important role in predisposing individuals to these modern diseases, we hypothesize that the extent to which antibiotics influence complex diseases depends on the host genome and metagenome. The current study tests this hypothesis in the context of hypertension, which is a serious risk factor for cardiovascular diseases. A 3 × 2 factorial design was used to test the blood pressure (BP) and microbiotal effects of three different antibiotics, neomycin, minocycline, and vancomycin, on two well-known, preclinical, genetic models of hypertension, the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR), both of which develop hypertension, but for different genetic reasons. Regardless of the class, oral administration of antibiotics increased systolic blood pressure of the S rat, while minocycline and vancomycin, but not neomycin, lowered systolic blood pressure in the SHR. These disparate BP effects were accompanied by significant alterations in gut microbiota. Our study highlights the need to consider an individualized approach for the usage of antibiotics among hypertensives, as their BP could be affected differentially based on their individual genetic and microbiotal communities.