Abstract P238: Bile Acid Metabolites Modulate Hypertension Meeting Abstract (Web of Science)

abstract

  • Hypertension is the single prominent risk factor of epidemic proportions leading to cardiovascular disease and stroke, which comprise the top two reasons for mortality of humans in the modern age. Much of the attention for the unknown causes of hypertension was focused on genetics and dietary salt, but in recent years, host-microbiotal interaction is gaining importance. Host-microbiotal partnership is key for the generation of many bioactive molecules including bile acid (BA) metabolites. Primary bile acids are synthesized and conjugated by the host but deconjugated and further modified to secondary BA by gut commensal bacteria. BA metabolites serve as important ligands for host nuclear receptors and/or G-protein-coupled receptors. These receptors have pivotal roles in blood pressure regulation. However, the effect of the host-microorganism biliary network on blood pressure (BP) remains poorly characterized. Here we report that both dietary salt and genetic factors rewire the composition of bile acids and BP. Specific reductions in conjugated bile acids were noted in human hypertensives as well as in rats with hypertension. Conjugation of bile acids by the host alone, devoid of the deconjugation step by microbiota, was sufficient to decrease BP of germ-free rats compared to germ-free conventionalized rats. Nutritional restoration of the conjugation of bile acids with Taurine increased the availability of circulating conjugated bile acids as ligands and ameliorated host susceptibility to hypertension via BA nuclear receptors and G-protein-coupled receptors. Thus, hosts and their bacterial symbionts can control host BP homeostasis via the resulting pool of bile acid metabolites. Sources of funding: National Institutes of Health (R01HL143082).

authors

  • CHAKRABORTY, Saroj
  • Lulla, Anju
  • Cheng, Xi
  • McCarthy, Cam
  • Yeo, Ji-Youn
  • Mandal, Juthika
  • Alimadadi, Ahmad
  • Saha, Piu
  • Yeoh, Beng San
  • Mell, Blair
  • Jia, Wei
  • Putluri, Vasanta
  • Putluri, Nagireddy
  • Sreekumar, Arun
  • Kumar, Matam Vijay
  • Meyer, Katie A
  • Joe, Bina

publication date

  • 2020

webpage

published in

volume

  • 76

issue

  • Suppl_1