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.

Association of Trimethylamine, Trimethylamine N-oxide, and Dimethylamine with Cardiovascular Risk in Children with Chronic Kidney Disease

“…This finding is in line with an animal study showing that minocycline-treated Dahl salt-sensitive rats developed hypertension related to a decrease in Cyanobacteria [42]. Although the Firmicutes-to-Bacteroidetes ratio has been linked to hypertension [41], we did not find the difference of this ratio between CKD children with normal and abnormal ABPM profile. The reason is possibly because we analyzed gut microbiota in CKD children preceding hypertension onset but not in the stage of established hypertension.…”

“…In the current study, CKD children with abnormal and normal ABPM associated into two distinct enterotypes, represented by β-diversity changes. Our data support the notion that gut microbiota is linked to the development of hypertension [40,41]. At the phylum level, the abundance of Cyanobacteria was lower in the abnormal vs. normal ABPM group.…”

The gut microbiota and its interactions with cardiovascular disease

“…Several cardiovascular experiments have focused on the elimination of bacterially induced diseases via antibiotics. For example, vancomycin and minocycline interventions decreased systolic BP in spontaneously hypertensive rats (Galla, et al , ). Furthermore, ampicillin reduced atherosclerotic risk factors, such as lipoprotein levels (Rune, et al , ).…”

Pregnane X Receptor Activator Rifampin Increases Blood Pressure and Stimulates Plasma Renin Activity

“…The activation of LXR-α by synthetic LXR agonists T0901317 and GW3965 have been shown to reduce the experimentally stimulated RAAS and/or BP. 18,[36][37][38][39] In contrast, both T0901317 and 22(R)-HC treatment elevated BP in mice with no prior hypertension-inducing procedures or treatments. 23 The interpretation of the T0901317 results is complicated by the finding that T0901317 has also some affinity for mouse PXR.…”