Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights

doi:10.1007/s11684-024-1055-9

Review

. 2024 Feb;18(1):31-45.

doi: 10.1007/s11684-024-1055-9. Epub 2024 Mar 1.

Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights

Yaonan Song^{1

2}, Haoran Wei^{1

2}, Zhitong Zhou^{1

2}, Huiqing Wang^{1

2}, Weijian Hang^{1

2}, Junfang Wu^{3

4}, Dao Wen Wang^{1

2}

Affiliations

¹ Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
² Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China.
³ Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. junfang.wu@tjh.tjmu.edu.cn.
⁴ Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China. junfang.wu@tjh.tjmu.edu.cn.

PMID: 38424375
DOI: 10.1007/s11684-024-1055-9

Review

Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights

Yaonan Song et al. Front Med. 2024 Feb.

. 2024 Feb;18(1):31-45.

doi: 10.1007/s11684-024-1055-9. Epub 2024 Mar 1.

Authors

Yaonan Song^{1

2}, Haoran Wei^{1

2}, Zhitong Zhou^{1

2}, Huiqing Wang^{1

2}, Weijian Hang^{1

2}, Junfang Wu^{3

4}, Dao Wen Wang^{1

2}

Affiliations

¹ Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
² Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China.
³ Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. junfang.wu@tjh.tjmu.edu.cn.
⁴ Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China. junfang.wu@tjh.tjmu.edu.cn.

PMID: 38424375
DOI: 10.1007/s11684-024-1055-9

Abstract

Phenylacetylglutamine (PAGln) is an amino acid derivate that comes from the amino acid phenylalanine. There are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular diseases. In this review, we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of PAGln. We summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases, such as heart failure, coronary heart disease/atherosclerosis, and cardiac arrhythmia. The underlying mechanism of PAGln is now considered to be related to the thrombotic potential of platelets via adrenergic receptors. Besides, other possible mechanisms such as inflammatory response and oxidative stress could also be induced by PAGln. Moreover, since PAGln is produced across different organs including the intestine, liver, and kidney, the cross-talk among multiple organs focused on the function of this uremic toxic metabolite. Finally, the prognostic value of PAGln compared to the classical biomarker was discussed and we also highlighted important gaps in knowledge and areas requiring future investigation of PAGln in cardiovascular diseases.

Keywords: PAGln; biomarker; cardiovascular disease; gut microbiota; uremic metabolite.

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[1] Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science 2005; 307(5717): 1915–1920 - PubMed

[2] Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science 2005; 307(5717): 1915–1920 - PubMed

[3] Fromentin S, Forslund SK, Chechi K, Aron-Wisnewsky J, Chakaroun R, Nielsen T, Tremaroli V, Ji B, Prifti E, Myridakis A, Chilloux J, Andrikopoulos P, Fan Y, Olanipekun MT, Alves R, Adiouch S, Bar N, Talmor-Barkan Y, Belda E, Caesar R, Coelho LP, Falony G, Fellahi S, Galan P, Galleron N, Helft G, Hoyles L, Isnard R, Le Chatelier E, Julienne H, Olsson L, Pedersen HK, Pons N, Quinquis B, Rouault C, Roume H, Salem JE, Schmidt TSB, Vieira-Silva S, Li P, Zimmermann-Kogadeeva M, Lewinter C, Sondertoft NB, Hansen TH, Gauguier D, Gøtze JP, Køber L, Kornowski R, Vestergaard H, Hansen T, Zucker JD, Hercberg S, Letunic I, Bäckhed F, Oppert JM, Nielsen J, Raes J, Bork P, Stumvoll M, Segal E, Clément K, Dumas ME, Ehrlich SD, Pedersen O. Microbiome and metabolome features of the cardiometabolic disease spectrum. Nat Med 2022; 28(2): 303–314 - PubMed - PMC

[4] Fromentin S, Forslund SK, Chechi K, Aron-Wisnewsky J, Chakaroun R, Nielsen T, Tremaroli V, Ji B, Prifti E, Myridakis A, Chilloux J, Andrikopoulos P, Fan Y, Olanipekun MT, Alves R, Adiouch S, Bar N, Talmor-Barkan Y, Belda E, Caesar R, Coelho LP, Falony G, Fellahi S, Galan P, Galleron N, Helft G, Hoyles L, Isnard R, Le Chatelier E, Julienne H, Olsson L, Pedersen HK, Pons N, Quinquis B, Rouault C, Roume H, Salem JE, Schmidt TSB, Vieira-Silva S, Li P, Zimmermann-Kogadeeva M, Lewinter C, Sondertoft NB, Hansen TH, Gauguier D, Gøtze JP, Køber L, Kornowski R, Vestergaard H, Hansen T, Zucker JD, Hercberg S, Letunic I, Bäckhed F, Oppert JM, Nielsen J, Raes J, Bork P, Stumvoll M, Segal E, Clément K, Dumas ME, Ehrlich SD, Pedersen O. Microbiome and metabolome features of the cardiometabolic disease spectrum. Nat Med 2022; 28(2): 303–314 - PubMed - PMC

[5] Talmor-Barkan Y, Bar N, Shaul AA, Shahaf N, Godneva A, Bussi Y, Lotan-Pompan M, Weinberger A, Shechter A, Chezar-Azerrad C, Arow Z, Hammer Y, Chechi K, Forslund SK, Fromentin S, Dumas ME, Ehrlich SD, Pedersen O, Kornowski R, Segal E. Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease. Nat Med 2022; 28(2): 295–302 - PubMed

[6] Talmor-Barkan Y, Bar N, Shaul AA, Shahaf N, Godneva A, Bussi Y, Lotan-Pompan M, Weinberger A, Shechter A, Chezar-Azerrad C, Arow Z, Hammer Y, Chechi K, Forslund SK, Fromentin S, Dumas ME, Ehrlich SD, Pedersen O, Kornowski R, Segal E. Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease. Nat Med 2022; 28(2): 295–302 - PubMed

[7] Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011; 472(7341): 57–63 - PubMed - PMC

[8] Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011; 472(7341): 57–63 - PubMed - PMC

[9] Tang TWH, Chen HC, Chen CY, Yen CYT, Lin CJ, Prajnamitra RP, Chen LL, Ruan SC, Lin JH, Lin PJ, Lu HH, Kuo CW, Chang CM, Hall AD, Vivas EI, Shui JW, Chen P, Hacker TA, Rey FE, Kamp TJ, Hsieh PCH. Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair. Circulation 2019; 139(5): 647–659 - PubMed

[10] Tang TWH, Chen HC, Chen CY, Yen CYT, Lin CJ, Prajnamitra RP, Chen LL, Ruan SC, Lin JH, Lin PJ, Lu HH, Kuo CW, Chang CM, Hall AD, Vivas EI, Shui JW, Chen P, Hacker TA, Rey FE, Kamp TJ, Hsieh PCH. Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair. Circulation 2019; 139(5): 647–659 - PubMed

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Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights

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Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights

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