Research progress of effect of gut microbiota and its metabolites on coronary artery diseases_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LI Zipeng , CHEN Wei ,  TIAN Hai

Department of Cardiovascular Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, P. R. China;

Corresponding author：

TIAN Hai, Email: doctor_tianhai@163.com

Keywords：

Gut microbiota; metabolites; trimethylamine N-oxide; coronary artery disease; review

DOI：

10.7507/1007-4848.202202047

Video：

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Gut microbiota and its metabolites in various human diseases have gradually become a research hotspot in the current medical community. And coronary artery disease is currently one of the most threatening clinical cardiovascular diseases in the world, so the use of gut microbiota and its metabolites in the development of its pathophysiology has also received more and more attention. Therefore, this paper reviews the effects of gut microbiota and its metabolites on coronary artery disease, as well as the research progress of intervening gut microbiota and its metabolites as therapeutic targets, hoping to expand the future research direction in this field and provide new ideas with treating coronary artery disease.

Citation： LI Zipeng, CHEN Wei, TIAN Hai. Research progress of effect of gut microbiota and its metabolites on coronary artery diseases. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(5): 761-765. doi: 10.7507/1007-4848.202202047 Copy

1.	Stolpe S, Kowall B, Stang A. Decline of coronary heart disease mortality is strongly effected by changing patterns of underlying causes of death: An analysis of mortality data from 27 countries of the WHO European region 2000 and 2013. Eur J Epidemiol, 2021, 36(1): 57-68.
2.	Tang TWH, Chen HC, Chen CY, et al. Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair. Circulation, 2019, 139(5): 647-659.
3.	Gul L, Modos D, Fonseca S, et al. Extracellular vesicles produced by the human commensal gut bacterium Bacteroides thetaiotaomicron affect host immune pathways in a cell-type specific manner that are altered in inflammatory bowel disease. J Extracell Vesicles, 2022, 11(1): e12189.
4.	Lin Y, Dong MQ, Liu ZM, et al. A strategy of vascular-targeted therapy for liver fibrosis. Hepatology, 2022, 76(3): 660-675.
5.	Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 2010, 464(7285): 59-65.
6.	Han Y, Gong Z, Sun G, et al. Dysbiosis of gut microbiota in patients with acute myocardial infarction. Front Microbiol, 2021, 12: 680101.
7.	Brown JM, Hazen SL. The gut microbial endocrine organ: Bacterially derived signals driving cardiometabolic diseases. Annu Rev Med, 2015, 66: 343-359.
8.	Yoshida N, Emoto T, Yamashita T, et al. Bacteroides vulgatus and Bacteroides dorei reduce gut microbial lipopolysaccharide production and inhibit atherosclerosis. Circulation, 2018, 138(22): 2486-2498.
9.	Pedersen HK, Gudmundsdottir V, Nielsen HB, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature, 2016, 535(7612): 376-381.
10.	Di Pino A, DeFronzo RA. Insulin resistance and atherosclerosis: Implications for insulin-sensitizing agents. Endocr Rev, 2019, 40(6): 1447-1467.
11.	Kovatcheva-Datchary P, Nilsson A, Akrami R, et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of prevotella. Cell Metab, 2015, 22(6): 971-982.
12.	Sandek A, Rauchhaus M, Anker SD, et al. The emerging role of the gut in chronic heart failure. Curr Opin Clin Nutr Metab Care, 2008, 11(5): 632-639.
13.	Wu P, Chen J, Chen J, et al. Trimethylamine N-oxide promotes apoE^–/– mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway. J Cell Physiol, 2020, 235(10): 6582-6591.
14.	Organ CL, Otsuka H, Bhushan S, et al. Choline diet and its gut microbe-derived metabolite, trimethylamine N-oxide, exacerbate pressure overload-induced heart failure. Circ Heart Fail, 2016, 9(1): e002314.
15.	Yang W, Zhang S, Zhu J, et al. Gut microbe-derived metabolite trimethylamine N-oxide accelerates fibroblast-myofibroblast differentiation and induces cardiac fibrosis. J Mol Cell Cardiol, 2019, 134: 119-130.
16.	Wang X, Luo D, Wu S. Molecular dysfunctions of mitochondria-associated endoplasmic reticulum contacts in atherosclerosis. Oxid Med Cell Longev, 2021, 2021: 2424509.
17.	Emoto T, Yamashita T, Kobayashi T, et al. Characterization of gut microbiota profiles in coronary artery disease patients using data mining analysis of terminal restriction fragment length polymorphism: Gut microbiota could be a diagnostic marker of coronary artery disease. Heart Vessels, 2017, 32(1): 39-46.
18.	Jie Z, Xia H, Zhong SL, et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun, 2017, 8(1): 845.
19.	Koren O, Spor A, Felin J, et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A, 2011, 108 Suppl 1(Suppl 1): 4592-4598.
20.	Seldin MM, Meng Y, Qi H, et al. Trimethylamine N-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear factor-κB. J Am Heart Assoc, 2016, 5(2): e002767.
21.	Brown AJ, Goldsworthy SM, Barnes AA, et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem, 2003, 278(13): 11312-11319.
22.	Miyamoto J, Kasubuchi M, Nakajima A, et al. The role of short-chain fatty acid on blood pressure regulation. Curr Opin Nephrol Hypertens, 2016, 25(5): 379-383.
23.	Tang WH, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res, 2017, 120(7): 1183-1196.
24.	Alsharairi NA. The role of short-chain fatty acids in the interplay between a very low-calorie ketogenic diet and the infant gut microbiota and its therapeutic implications for reducing asthma. Int J Mol Sci, 2020, 21(24): 9580.
25.	Poll BG, Xu J, Jun S, et al. Acetate, a short-chain fatty acid, acutely lowers heart rate and cardiac contractility along with blood pressure. J Pharmacol Exp Ther, 2021, 377(1): 39-50.
26.	Bartolomaeus H, Balogh A, Yakoub M, et al. Short-chain fatty acid propionate protects from hypertensive cardiovascular damage. Circulation, 2019, 139(11): 1407-1421.
27.	Onyszkiewicz M, Gawrys-Kopczynska M, Konopelski P, et al. Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors. Pflugers Arch, 2019, 471(11-12): 1441-1453.
28.	Hageman J, Herrema H, Groen AK, et al. A role of the bile salt receptor FXR in atherosclerosis. Arterioscler Thromb Vasc Biol, 2010, 30(8): 1519-1528.
29.	Li YT, Swales KE, Thomas GJ, et al. Farnesoid x receptor ligands inhibit vascular smooth muscle cell inflammation and migration. Arterioscler Thromb Vasc Biol, 2007, 27(12): 2606-2611.
30.	Coutinho-Wolino KS, de F Cardozo LFM, de Oliveira Leal V, et al. Can diet modulate trimethylamine N-oxide (TMAO) production? What do we know so far? Eur J Nutr, 2021, 60(7): 3567-3584.
31.	Liu Y, Dai M. Trimethylamine N-oxide generated by the gut microbiota is associated with vascular inflammation: New insights into atherosclerosis. Mediators Inflamm, 2020, 2020: 4634172.
32.	Martínez-Del Campo A, Romano KA, Rey FE, et al. The plot thickens: Diet microbe interactions may modulate thrombosis risk. Cell Metab, 2016, 23(4): 573-575.
33.	Li XS, Obeid S, Klingenberg R, et al. Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: A prognostic marker for incident cardiovascular events beyond traditional risk factors. Eur Heart J, 2017, 38(11): 814-824.
34.	Cui X, Ye L, Li J, et al. Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients. Sci Rep, 2018, 8(1): 635.
35.	Chen ML, Zhu XH, Ran L, et al. Trimethylamine-N-oxide induces vascular inflammation by activating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway. J Am Heart Assoc, 2017, 6(9): e006347.
36.	Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science, 2011, 334(6052): 105-108.
37.	Wang Z, Bergeron N, Levison BS, et al. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur Heart J, 2019, 40(7): 583-594.
38.	Trefz F, Maillot F, Motzfeldt K, et al. Adult phenylketonuria outcome and management. Mol Genet Metab, 2011, 104 Suppl: S26-S30.
39.	Pakhomov N, Baugh JA. The role of diet-derived short-chain fatty acids in regulating cardiac pressure overload. Am J Physiol Heart Circ Physiol, 2021, 320(2): H475-H486.
40.	Lim RRX, Park MA, Wong LH, et al. Gut microbiome responses to dietary intervention with hypocholesterolemic vegetable oils. NPJ Biofilms Microbiomes, 2022, 8(1): 24.
41.	Jin M, Qian Z, Yin J, et al. The role of intestinal microbiota in cardiovascular disease. J Cell Mol Med, 2019, 23(4): 2343-2350.
42.	Vasquez EC, Pereira TMC, Peotta VA, et al. Probiotics as beneficial dietary supplements to prevent and treat cardiovascular diseases: Uncovering their impact on oxidative stress. Oxid Med Cell Longev, 2019, 2019: 3086270.
43.	Costello SP, Soo W, Bryant RV, et al. Systematic review with meta-analysis: Faecal microbiota transplantation for the induction of remission for active ulcerative colitis. Aliment Pharmacol Ther, 2017, 46(3): 213-224.
44.	Paramsothy S, Paramsothy R, Rubin DT, et al. Faecal microbiota transplantation for inflammatory bowel disease: A systematic review and meta-analysis. J Crohns Colitis, 2017, 11(10): 1180-1199.
45.	Imdad A, Nicholson MR, Tanner-Smith EE, et al. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev, 2018, 11(11): CD012774.
46.	Zhu W, Gregory JC, Org E, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell, 2016, 165(1): 111-124.
47.	Wang Z, Roberts AB, Buffa JA, et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell, 2015, 163(7): 1585-1595.
48.	Dannenberg L, Zikeli D, Benkhoff M, et al. Targeting the human microbiome and its metabolite TMAO in cardiovascular prevention and therapy. Pharmacol Ther, 2020, 213: 107584.
49.	Roberts AB, Gu X, Buffa JA, et al. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nat Med, 2018, 24(9): 1407-1417.
50.	Liu Y, Liu S, Zhao Z, et al. Phenylacetylglutamine is associated with the degree of coronary atherosclerotic severity assessed by coronary computed tomographic angiography in patients with suspected coronary artery disease. Atherosclerosis, 2021, 333: 75-82.
51.	Nemet I, Saha PP, Gupta N, et al. A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors. Cell, 2020, 180(5): 862-877.

1. Stolpe S, Kowall B, Stang A. Decline of coronary heart disease mortality is strongly effected by changing patterns of underlying causes of death: An analysis of mortality data from 27 countries of the WHO European region 2000 and 2013. Eur J Epidemiol, 2021, 36(1): 57-68.
2. Tang TWH, Chen HC, Chen CY, et al. Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair. Circulation, 2019, 139(5): 647-659.
3. Gul L, Modos D, Fonseca S, et al. Extracellular vesicles produced by the human commensal gut bacterium Bacteroides thetaiotaomicron affect host immune pathways in a cell-type specific manner that are altered in inflammatory bowel disease. J Extracell Vesicles, 2022, 11(1): e12189.
4. Lin Y, Dong MQ, Liu ZM, et al. A strategy of vascular-targeted therapy for liver fibrosis. Hepatology, 2022, 76(3): 660-675.
5. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 2010, 464(7285): 59-65.
6. Han Y, Gong Z, Sun G, et al. Dysbiosis of gut microbiota in patients with acute myocardial infarction. Front Microbiol, 2021, 12: 680101.
7. Brown JM, Hazen SL. The gut microbial endocrine organ: Bacterially derived signals driving cardiometabolic diseases. Annu Rev Med, 2015, 66: 343-359.
8. Yoshida N, Emoto T, Yamashita T, et al. Bacteroides vulgatus and Bacteroides dorei reduce gut microbial lipopolysaccharide production and inhibit atherosclerosis. Circulation, 2018, 138(22): 2486-2498.
9. Pedersen HK, Gudmundsdottir V, Nielsen HB, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature, 2016, 535(7612): 376-381.
10. Di Pino A, DeFronzo RA. Insulin resistance and atherosclerosis: Implications for insulin-sensitizing agents. Endocr Rev, 2019, 40(6): 1447-1467.
11. Kovatcheva-Datchary P, Nilsson A, Akrami R, et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of prevotella. Cell Metab, 2015, 22(6): 971-982.
12. Sandek A, Rauchhaus M, Anker SD, et al. The emerging role of the gut in chronic heart failure. Curr Opin Clin Nutr Metab Care, 2008, 11(5): 632-639.
13. Wu P, Chen J, Chen J, et al. Trimethylamine N-oxide promotes apoE^–/– mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway. J Cell Physiol, 2020, 235(10): 6582-6591.
14. Organ CL, Otsuka H, Bhushan S, et al. Choline diet and its gut microbe-derived metabolite, trimethylamine N-oxide, exacerbate pressure overload-induced heart failure. Circ Heart Fail, 2016, 9(1): e002314.
15. Yang W, Zhang S, Zhu J, et al. Gut microbe-derived metabolite trimethylamine N-oxide accelerates fibroblast-myofibroblast differentiation and induces cardiac fibrosis. J Mol Cell Cardiol, 2019, 134: 119-130.
16. Wang X, Luo D, Wu S. Molecular dysfunctions of mitochondria-associated endoplasmic reticulum contacts in atherosclerosis. Oxid Med Cell Longev, 2021, 2021: 2424509.
17. Emoto T, Yamashita T, Kobayashi T, et al. Characterization of gut microbiota profiles in coronary artery disease patients using data mining analysis of terminal restriction fragment length polymorphism: Gut microbiota could be a diagnostic marker of coronary artery disease. Heart Vessels, 2017, 32(1): 39-46.
18. Jie Z, Xia H, Zhong SL, et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun, 2017, 8(1): 845.
19. Koren O, Spor A, Felin J, et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A, 2011, 108 Suppl 1(Suppl 1): 4592-4598.
20. Seldin MM, Meng Y, Qi H, et al. Trimethylamine N-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear factor-κB. J Am Heart Assoc, 2016, 5(2): e002767.
21. Brown AJ, Goldsworthy SM, Barnes AA, et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem, 2003, 278(13): 11312-11319.
22. Miyamoto J, Kasubuchi M, Nakajima A, et al. The role of short-chain fatty acid on blood pressure regulation. Curr Opin Nephrol Hypertens, 2016, 25(5): 379-383.
23. Tang WH, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res, 2017, 120(7): 1183-1196.
24. Alsharairi NA. The role of short-chain fatty acids in the interplay between a very low-calorie ketogenic diet and the infant gut microbiota and its therapeutic implications for reducing asthma. Int J Mol Sci, 2020, 21(24): 9580.
25. Poll BG, Xu J, Jun S, et al. Acetate, a short-chain fatty acid, acutely lowers heart rate and cardiac contractility along with blood pressure. J Pharmacol Exp Ther, 2021, 377(1): 39-50.
26. Bartolomaeus H, Balogh A, Yakoub M, et al. Short-chain fatty acid propionate protects from hypertensive cardiovascular damage. Circulation, 2019, 139(11): 1407-1421.
27. Onyszkiewicz M, Gawrys-Kopczynska M, Konopelski P, et al. Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors. Pflugers Arch, 2019, 471(11-12): 1441-1453.
28. Hageman J, Herrema H, Groen AK, et al. A role of the bile salt receptor FXR in atherosclerosis. Arterioscler Thromb Vasc Biol, 2010, 30(8): 1519-1528.
29. Li YT, Swales KE, Thomas GJ, et al. Farnesoid x receptor ligands inhibit vascular smooth muscle cell inflammation and migration. Arterioscler Thromb Vasc Biol, 2007, 27(12): 2606-2611.
30. Coutinho-Wolino KS, de F Cardozo LFM, de Oliveira Leal V, et al. Can diet modulate trimethylamine N-oxide (TMAO) production? What do we know so far? Eur J Nutr, 2021, 60(7): 3567-3584.
31. Liu Y, Dai M. Trimethylamine N-oxide generated by the gut microbiota is associated with vascular inflammation: New insights into atherosclerosis. Mediators Inflamm, 2020, 2020: 4634172.
32. Martínez-Del Campo A, Romano KA, Rey FE, et al. The plot thickens: Diet microbe interactions may modulate thrombosis risk. Cell Metab, 2016, 23(4): 573-575.
33. Li XS, Obeid S, Klingenberg R, et al. Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: A prognostic marker for incident cardiovascular events beyond traditional risk factors. Eur Heart J, 2017, 38(11): 814-824.
34. Cui X, Ye L, Li J, et al. Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients. Sci Rep, 2018, 8(1): 635.
35. Chen ML, Zhu XH, Ran L, et al. Trimethylamine-N-oxide induces vascular inflammation by activating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway. J Am Heart Assoc, 2017, 6(9): e006347.
36. Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science, 2011, 334(6052): 105-108.
37. Wang Z, Bergeron N, Levison BS, et al. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur Heart J, 2019, 40(7): 583-594.
38. Trefz F, Maillot F, Motzfeldt K, et al. Adult phenylketonuria outcome and management. Mol Genet Metab, 2011, 104 Suppl: S26-S30.
39. Pakhomov N, Baugh JA. The role of diet-derived short-chain fatty acids in regulating cardiac pressure overload. Am J Physiol Heart Circ Physiol, 2021, 320(2): H475-H486.
40. Lim RRX, Park MA, Wong LH, et al. Gut microbiome responses to dietary intervention with hypocholesterolemic vegetable oils. NPJ Biofilms Microbiomes, 2022, 8(1): 24.
41. Jin M, Qian Z, Yin J, et al. The role of intestinal microbiota in cardiovascular disease. J Cell Mol Med, 2019, 23(4): 2343-2350.
42. Vasquez EC, Pereira TMC, Peotta VA, et al. Probiotics as beneficial dietary supplements to prevent and treat cardiovascular diseases: Uncovering their impact on oxidative stress. Oxid Med Cell Longev, 2019, 2019: 3086270.
43. Costello SP, Soo W, Bryant RV, et al. Systematic review with meta-analysis: Faecal microbiota transplantation for the induction of remission for active ulcerative colitis. Aliment Pharmacol Ther, 2017, 46(3): 213-224.
44. Paramsothy S, Paramsothy R, Rubin DT, et al. Faecal microbiota transplantation for inflammatory bowel disease: A systematic review and meta-analysis. J Crohns Colitis, 2017, 11(10): 1180-1199.
45. Imdad A, Nicholson MR, Tanner-Smith EE, et al. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev, 2018, 11(11): CD012774.
46. Zhu W, Gregory JC, Org E, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell, 2016, 165(1): 111-124.
47. Wang Z, Roberts AB, Buffa JA, et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell, 2015, 163(7): 1585-1595.
48. Dannenberg L, Zikeli D, Benkhoff M, et al. Targeting the human microbiome and its metabolite TMAO in cardiovascular prevention and therapy. Pharmacol Ther, 2020, 213: 107584.
49. Roberts AB, Gu X, Buffa JA, et al. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nat Med, 2018, 24(9): 1407-1417.
50. Liu Y, Liu S, Zhao Z, et al. Phenylacetylglutamine is associated with the degree of coronary atherosclerotic severity assessed by coronary computed tomographic angiography in patients with suspected coronary artery disease. Atherosclerosis, 2021, 333: 75-82.
51. Nemet I, Saha PP, Gupta N, et al. A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors. Cell, 2020, 180(5): 862-877.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Research progress of effect of gut microbiota and its metabolites on coronary artery diseases

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