Conjugated bile acids are nutritionally re-programmable antihypertensive metabolites

Saroj Chakraborty; Anju Lulla; Xi Cheng; Ji Youn Yeo; Juthika Mandal; Tao Yang; Xue Mei; Piu Saha; Rachel M. Golonka; Beng San Yeoh; Blair Mell; Wei Jia; Vasanta Putluri; Danthasinghe Waduge Badrajee Piyarathna; Nagireddy Putluri; Arun Sreekumar; Katie Meyer; Matam Vijay-Kumar; Bina Joe

doi:10.1097/HJH.0000000000003423

Conjugated bile acids are nutritionally re-programmable antihypertensive metabolites

Saroj Chakraborty, Anju Lulla, Xi Cheng, Ji Youn Yeo, Juthika Mandal, Tao Yang, Xue Mei, Piu Saha, Rachel M. Golonka, Beng San Yeoh, Blair Mell, Wei Jia, Vasanta Putluri, Danthasinghe Waduge Badrajee Piyarathna, Nagireddy Putluri, Arun Sreekumar, Katie Meyer, Matam Vijay-Kumar, Bina Joe^*

^*Corresponding author for this work

Chinese Medicine - Teaching and Research Division

Research output: Contribution to journal › Journal article › peer-review

8 Citations (Scopus)

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.

Original language	English
Pages (from-to)	979-994
Number of pages	16
Journal	Journal of Hypertension
Volume	41
Issue number	6
DOIs	https://doi.org/10.1097/HJH.0000000000003423
Publication status	Published - Jun 2023

Scopus Subject Areas

Internal Medicine
Physiology
Cardiology and Cardiovascular Medicine

User-Defined Keywords

bile acids
conjugated bile acids
hypertension
metabolomics
salt-sensitive hypertension
taurine
tauro-cholic acid

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/HJH.0000000000003423

Cite this

Chakraborty, S., Lulla, A., Cheng, X., Yeo, J. Y., Mandal, J., Yang, T., Mei, X., Saha, P., Golonka, R. M., Yeoh, B. S., Mell, B., Jia, W., Putluri, V., Piyarathna, D. W. B., Putluri, N., Sreekumar, A., Meyer, K., Vijay-Kumar, M., & Joe, B. (2023). Conjugated bile acids are nutritionally re-programmable antihypertensive metabolites. Journal of Hypertension, 41(6), 979-994. https://doi.org/10.1097/HJH.0000000000003423

@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 Ltd.",

number = "6",

}

Chakraborty, S, Lulla, A, Cheng, X, Yeo, JY, Mandal, J, Yang, T, Mei, X, Saha, P, Golonka, RM, Yeoh, BS, Mell, B, Jia, W, Putluri, V, Piyarathna, DWB, Putluri, N, Sreekumar, A, Meyer, K, Vijay-Kumar, M & Joe, B 2023, 'Conjugated bile acids are nutritionally re-programmable antihypertensive metabolites', Journal of Hypertension, vol. 41, no. 6, pp. 979-994. https://doi.org/10.1097/HJH.0000000000003423

TY - JOUR

T1 - Conjugated bile acids are nutritionally re-programmable antihypertensive metabolites

AU - Chakraborty, Saroj

AU - Lulla, Anju

AU - Cheng, Xi

AU - Yeo, Ji Youn

AU - Mandal, Juthika

AU - Yang, Tao

AU - Mei, Xue

AU - Saha, Piu

AU - Golonka, Rachel M.

AU - Yeoh, Beng San

AU - Mell, Blair

AU - Jia, Wei

AU - Putluri, Vasanta

AU - Piyarathna, Danthasinghe Waduge Badrajee

AU - Putluri, Nagireddy

AU - Sreekumar, Arun

AU - Meyer, Katie

AU - Vijay-Kumar, Matam

AU - Joe, Bina

N1 - 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: © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

PY - 2023/6

Y1 - 2023/6

N2 - 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.

AB - 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.

KW - bile acids

KW - conjugated bile acids

KW - hypertension

KW - metabolomics

KW - salt-sensitive hypertension

KW - taurine

KW - tauro-cholic acid

UR - http://www.scopus.com/inward/record.url?scp=85158838595&partnerID=8YFLogxK

U2 - 10.1097/HJH.0000000000003423

DO - 10.1097/HJH.0000000000003423

M3 - Journal article

C2 - 37071431

AN - SCOPUS:85158838595

SN - 0263-6352

VL - 41

SP - 979

EP - 994

JO - Journal of Hypertension

JF - Journal of Hypertension

IS - 6

ER -

Conjugated bile acids are nutritionally re-programmable antihypertensive metabolites

Abstract

Scopus Subject Areas

User-Defined Keywords

UN SDGs

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