Human Genomics

Featured article: Metabolomic profiling of metoprolol hypertension treatment reveals altered gut microbiota-derived urinary metabolites

Metoprolol succinate is a long-acting beta-blocker prescribed for the management of hypertension (HTN) and other cardiovascular diseases. Metabolomics, the study of end-stage metabolites of upstream biologic processes, yield insight into mechanisms of drug effectiveness and safety. Our aim was to determine metabolomic profiles associated with metoprolol effectiveness for the treatment of hypertension.Urinary metoprolol metabolite ratios are indicative of patient CYP2D6 genotypes. Patients taking metoprolol had significantly higher urinary levels of many gut microbiota-dependent metabolites including hydroxyhippuric acid, hippuric acid, and methyluric acid. Urinary metoprolol metabolite profiles of normal metabolizer (NM) patients more closely correlate to ultra-rapid metabolizer (UM) patients than NM patients. Metabolites did not predict either 10% SBP or HR decline.
In summary, in the treatment of HTN, metoprolol therapy appears to alter the gut microbiome and the composition of the microbiome may be an important factor in the effectiveness of antihypertensive drugs. Further work should focus on the stratification of drug effectiveness and gut microbiome composition in order to understand the biologic interactions between these systems.