Gut microbial metabolite connections to cardiovascular disease call for gutsy therapeutic approaches

Cardiovascular diseases (CVDs) currently account for over 40% of mortality in aging populations worldwide (1). Despite aggressive management of traditional cardiovascular and cardiometabolic risk factors such as LDL cholesterol, hypertension, and diabetes and despite advances in gerotherapeutics, including senolytics, mTOR inhibitors, AMPK activators, and NAD+ boosters, a powerful and modifiable determinant of cardiovascular aging remains underappreciated: the gut microbiota. Throughout the twentieth century, scattered observations suggested that gut microbes shape host physiology, but the complexity and dynamic nature of microbial communities have historically eclipsed the tools available to interrogate them. The advent of high-throughput microbiome sequencing, coupled with untargeted metabolomics, in the early twenty-first century transformed the field and established the gut microbiota as a key regulator of human health (2). Moving beyond documenting association and pursuing more mechanistic investigations of microbe-host physiology will require coupling integrative functional studies that connect microbial metabolites to host biology, with translational trials testing whether targeting microbial functions can prevent or ameliorate CVD in aging. Here, we summarize mechanistic evidence linking microbial metabolites to CVD risk, examine their validity as early biomarkers, and describe interventional approaches aimed at modifying microbial function to improve cardiovascular and cardiometabolic health with the aim of motivating collaboration between microbiome and cardiovascular research efforts. Gut microbial metabolites modify CVD risk Beginning in the 1970s and 1980s, changes in gut […]