@article{dabf101c2dde43d2a04d1878a70229d1,
title = "Conjugated bile acids are nutritionally re-programmable antihypertensive metabolites",
abstract = "Background: Hypertension is the largest risk factor affecting global mortality. Despite available medications, uncontrolled hypertension is on the rise, whereby there is an urgent need to develop novel and sustainable therapeutics. Because gut microbiota is now recognized as an important entity in blood pressure regulation, one such new avenue is to target the gut-liver axis wherein metabolites are transacted via host-microbiota interactions. Knowledge on which metabolites within the gut-liver axis regulate blood pressure is largely unknown.Method: To address this, we analyzed bile acid profiles of human, hypertensive and germ-free rat models and report that conjugated bile acids are inversely correlated with blood pressure in humans and rats.Results: Notably intervening with taurine or tauro-cholic acid rescued bile acid conjugation and reduced blood pressure in hypertensive rats. Subsequently, untargeted metabolomics uncovered altered energy metabolism following conjugation of bile acids as a mechanism alleviating high blood pressure.Conclusion: Together this work reveals conjugated bile acids as nutritionally re-programmable anti-hypertensive metabolites.",
keywords = "bile acids, conjugated bile acids, hypertension, metabolomics, salt-sensitive hypertension, taurine, tauro-cholic acid",
author = "Saroj Chakraborty and Anju Lulla and Xi Cheng and Yeo, {Ji Youn} and Juthika Mandal and Tao Yang and Xue Mei and Piu Saha and Golonka, {Rachel M.} and Yeoh, {Beng San} and Blair Mell and Wei Jia and Vasanta Putluri and Piyarathna, {Danthasinghe Waduge Badrajee} and Nagireddy Putluri and Arun Sreekumar and Katie Meyer and Matam Vijay-Kumar and Bina Joe",
note = "Funding information: This work was supported by grants from the National Institutes of Health to B. Joe (HL1430820). This project was supported by CPRIT Proteomics and Metabolomics Core Facility (N.P.), (RP210227), NIH (P30 CA125123), and Dan L. Duncan Cancer Center. M.V.-K. is supported by NIH-R01 (CA219144). P. Saha is supported by American Heart Association (AHA), Career Development Award (# 855256). B.S. Yeoh is supported by AHA Postdoctoral Fellowship (# 831112). The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201800003I, HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, and HHSN268201800007I from the National Heart, Lung, and Blood Institute (NHLBI). Bile acid analysis in CARDIA was supported by K01- HL127159 and the University of North Carolina at Chapel Hill Nutrition Research Institute. Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Wolters Kluwer Health, Inc.",
year = "2023",
month = jun,
doi = "10.1097/HJH.0000000000003423",
language = "English",
volume = "41",
pages = "979--994",
journal = "Journal of Hypertension",
issn = "0263-6352",
publisher = "Lippincott Williams and Wilkins",
number = "6",
}
