Research progress on the relationship between gut microbiota, their metabolites, and aortic diseases_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LUO Xiaokang ¹ , SHAO Dantong ² , SUN Tucheng ¹ ,  YAN Xinjian ^1,3

1. Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, P. R. China;
2. Department of Women's Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, P. R. China;
3. Xinjiang Key Laboratory of Artificial Intelligence Assisted Imaging Diagnosis, Kashi, 844099, Xinjiang, P. R. China;

Corresponding?author：

YAN Xinjian, Email: yanxinjian@gdph.org.cn

Keywords：

Aortic disease; aortic aneurysm; aortic dissection; gut microbiome; gut dysbiosis; microbial metabolites

DOI：

10.7507/1007-4848.202412067

Video：

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The pathogenesis of aortic disease is not fully understood. Gut dysbiosis may play a role in the occurrence and development of aortic diseases. Several studies showed that the diversity of microbiota in abdominal aortic aneurysms significantly decreases and is correlated with the diameter of the aneurysm. Characteristic microbial communities associated with abdominal aortic aneurysm, such as Roseburia, Bifidobacterium, Ruminococcus, Akkermansia have been found in human and animal studies. The gut microbiota of patients with aortic dissection varies greatly. Characteristic microbial communities like Lachnospiraceae and Ruminococcus present a potential impact on the pathogenesis of aortic dissection. Bifidobacteriaceae may be associated with Takayasu arteritis and thoracic aortic aneurysm. The gut microbiota affects the physiological functions of the host by synthesizing bioactive metabolites, which causes aortic diseases, mainly involving metabolites such as trimethylamine N-oxide, lipopolysaccharides, tryptophan, and short chain fatty acids. More and more evidence supports the causal relationship between gut microbiota dysbiosis and aortic disease. Clarifying abnormal changes in gut microbiota may provide clues for finding potential therapeutic targets.

Citation： LUO Xiaokang, SHAO Dantong, SUN Tucheng, YAN Xinjian. Research progress on the relationship between gut microbiota, their metabolites, and aortic diseases. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2026, 33(8): 1330-1336. doi: 10.7507/1007-4848.202412067 Copy

1.	Zhang Y, Wang H, Sang Y, et al. Gut microbiota in health and disease: advances and future prospects[J/OL]. MedComm (2020), 2024, 5(12): e70012. DOI: 10.1002/mco2.70012.
2.	Kunath BJ, De Rudder C, Laczny CC, et al. The oral-gut microbiome axis in health and disease[J]. Nat Rev Microbiol, 2024, 22(12): 791-805.
3.	Chui ESH, Chan AKY, Ng ACK, et al. Mechanism and clinical implication of gut dysbiosis in degenerative abdominal aortic aneurysm: a systematic review[J]. Asian J Surg, 2024, 47(12): 5088-5095.
4.	Ling X, Jie W, Qin X, et al. Gut microbiome sheds light on the development and treatment of abdominal aortic aneurysm[J]. Front Cardiovasc Med, 2022, 9: 1063683.
5.	Shinohara R, Nakashima H, Emoto T, et al. Gut microbiota influence the development of abdominal aortic aneurysm by suppressing macrophage accumulation in mice[J]. Hypertension, 2022, 79(12): 2821-2829.
6.	Benson TW, Conrad KA, Li XS, et al. Gut microbiota-derived trimethylamine N-oxide contributes to abdominal aortic aneurysm through inflammatory and apoptotic mechanisms[J]. Circulation, 2023, 147(14): 1079-1096.
7.	Xiao J, Wei Z, Yang C, et al. The gut microbiota in experimental abdominal aortic aneurysm[J]. Front Cardiovasc Med, 2023, 10: 1051648.
8.	Liu S, Liu Y, Zhao J, et al. Effects of spermidine on gut microbiota modulation in experimental abdominal aortic aneurysm mice[J]. Nutrients, 2022, 14(16): 3349.
9.	Zhang K, Yang S, Huang Y et al. Alterations in gut microbiota and physiological factors associated with abdominal aortic aneurysm[J]. Med Nov Technol Devices, 2022, 14: 100122.
10.	Tian Z, Zhang Y, Zheng Z, et al. Gut microbiome dysbiosis contributes to abdominal aortic aneurysm by promoting neutrophil extracellular trap formation[J]. Cell Host Microbe, 2022, 30(10): 1450-1463.
11.	Ito E, Ohki T, Toya N, et al. Impact of bifidobacterium adolescentis in patients with abdominal aortic aneurysm: a cross-sectional study[J]. Biosci Microbiota Food Health, 2023, 42(1): 81-86.
12.	Nakayama K, Furuyama T, Matsubara Y, et al. Gut dysbiosis and bacterial translocation in the aneurysmal wall and blood in patients with abdominal aortic aneurysm[J/OL]. PLoS One, 2022, 17(12): e0278995. DOI: 10.1371/journal.pone.0278995.
13.	Nemes-Nikodém é, Gyurok GP, Dunai ZA, et al. Relationship between gut, blood, aneurysm wall and thrombus microbiome in abdominal aortic aneurysm patients[J]. Int J Mol Sci, 2024, 25(16): 8844.
14.	Xie J, Lu W, Zhong L, et al. Alterations in gut microbiota of abdominal aortic aneurysm mice[J]. BMC Cardiovasc Disord, 2020, 20(1): 32.
15.	He X, Bai Y, Zhou H, et al. Akkermansia muciniphila alters gut microbiota and immune system to improve cardiovascular diseases in murine model[J]. Front Microbiol, 2022, 13: 906920.
16.	Li C, Liu Z, Yang S, et al. Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study[J]. Clin Exp Hypertens, 2024, 46(1): 2390419.
17.	Qiu Y, Hou Y, Wei X, et al. Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study[J]. Front Microbiol, 2024, 15: 1267888.
18.	Lv Y, Shen D, Zhang G, et al. Causal associations between the gut microbiome and aortic aneurysm: a Mendelian randomization study[J]. Cardiovasc Innov Appl, 2024, 9(1): 956.
19.	Zhou X, Ruan W, Wang T, et al. Exploring the impact of gut microbiota on abdominal aortic aneurysm risk through a bidirectional Mendelian randomization analysis[J]. J Vasc Surg, 2024, 79(4): 763-775.
20.	Jiang F, Cai M, Peng Y, et al. Changes in the gut microbiome of patients with type a aortic dissection[J]. Front Microbiol, 2023, 14: 1092360.
21.	Huang S, Gao S, Shao Y, et al. Gut microbial metabolite trimethylamine N-oxide induces aortic dissection[J]. J Mol Cell Cardiol, 2024, 189: 25-37.
22.	Yesitayi G, Wang Q, Wang M, et al. LPS-LBP complex induced endothelial cell pyroptosis in aortic dissection is associated with gut dysbiosis[J]. Microbes Infect, 2024, 105406.
23.	Sun Y, Dong H, Sun C, et al. Investigating the association between gut microbiome and aortic aneurysm diseases: a bidirectional two-sample Mendelian randomization analysis[J]. Front Cell Infect Microbiol, 2024, 14: 1406845.
24.	Li D, Li F, Jin J et al. Unraveling the causal nexus: exploring the relationship between gut microbiota and aortic dissection[PP/OL]. Res Square (2023-08-31) [2024-11-01], 2023.
25.	Manabe Y, Ishibashi T, Asano R, et al. Gut dysbiosis is associated with aortic aneurysm formation and progression in Takayasu arteritis[J]. Arthritis Res Ther, 2023, 25(1): 46.
26.	Witkowski M, Witkowski M, Friebel J, et al. Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis[J]. Cardiovasc Res, 2022, 118(10): 2367-2384.
27.	Wang Q, Yesitayi G, Liu B, et al. Targeting metabolism in aortic aneurysm and dissection: from basic research to clinical applications[J]. Int J Biol Sci, 2023, 19(12): 3869-3891.
28.	Salhi L, Rijkschroeff P, Van Hede D, et al. Blood biomarkers and serologic immunological profiles related to periodontitis in abdominal aortic aneurysm patients[J]. front cell infect microbiol, 2022, 11: 766462.
29.	Ramprasath T, Han YM, Zhang D, et al. Tryptophan catabolism and inflammation: a novel therapeutic target for aortic diseases[J]. Front Immunol, 2021, 12: 731701.
30.	Wang Q, Lv H, Ainiwan M, et al. Untargeted metabolomics identifies indole-3-propionic acid to relieve Ang Ⅱ-induced endothelial dysfunction in aortic dissection[J]. Mol Cell Biochem, 2024, 479(7): 1767-1786.
31.	Huang SS, Liu R, Chang S, et al. Gut microbiota-derived tryptophan metabolite indole-3-aldehyde ameliorates aortic dissection[J]. Nutrients, 2023, 15(19): 4150.
32.	den Besten G, van Eunen K, Groen AK, et al. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism[J]. J Lipid Res, 2013, 54(9): 2325-2340.
33.	Yang F, Xia N, Guo S, et al. Propionate alleviates abdominal aortic aneurysm by modulating colonic regulatory T-cell expansion and recirculation[J]. JACC Basic Transl Sci, 2022, 7(9): 934-947.
34.	Forte A, Grossi M, Bancone C, et al. Polyamine concentration is increased in thoracic ascending aorta of patients with bicuspid aortic valve[J]. Heart Vessels, 2018, 33(3): 327-339.
35.	Forte A, Balistreri CR, De Feo M, et al. Polyamines and microbiota in bicuspid and tricuspid aortic valve aortopathy[J]. J Mol Cell Cardiol, 2019, 129: 179-187.

1. Zhang Y, Wang H, Sang Y, et al. Gut microbiota in health and disease: advances and future prospects[J/OL]. MedComm (2020), 2024, 5(12): e70012. DOI: 10.1002/mco2.70012.
2. Kunath BJ, De Rudder C, Laczny CC, et al. The oral-gut microbiome axis in health and disease[J]. Nat Rev Microbiol, 2024, 22(12): 791-805.
3. Chui ESH, Chan AKY, Ng ACK, et al. Mechanism and clinical implication of gut dysbiosis in degenerative abdominal aortic aneurysm: a systematic review[J]. Asian J Surg, 2024, 47(12): 5088-5095.
4. Ling X, Jie W, Qin X, et al. Gut microbiome sheds light on the development and treatment of abdominal aortic aneurysm[J]. Front Cardiovasc Med, 2022, 9: 1063683.
5. Shinohara R, Nakashima H, Emoto T, et al. Gut microbiota influence the development of abdominal aortic aneurysm by suppressing macrophage accumulation in mice[J]. Hypertension, 2022, 79(12): 2821-2829.
6. Benson TW, Conrad KA, Li XS, et al. Gut microbiota-derived trimethylamine N-oxide contributes to abdominal aortic aneurysm through inflammatory and apoptotic mechanisms[J]. Circulation, 2023, 147(14): 1079-1096.
7. Xiao J, Wei Z, Yang C, et al. The gut microbiota in experimental abdominal aortic aneurysm[J]. Front Cardiovasc Med, 2023, 10: 1051648.
8. Liu S, Liu Y, Zhao J, et al. Effects of spermidine on gut microbiota modulation in experimental abdominal aortic aneurysm mice[J]. Nutrients, 2022, 14(16): 3349.
9. Zhang K, Yang S, Huang Y et al. Alterations in gut microbiota and physiological factors associated with abdominal aortic aneurysm[J]. Med Nov Technol Devices, 2022, 14: 100122.
10. Tian Z, Zhang Y, Zheng Z, et al. Gut microbiome dysbiosis contributes to abdominal aortic aneurysm by promoting neutrophil extracellular trap formation[J]. Cell Host Microbe, 2022, 30(10): 1450-1463.
11. Ito E, Ohki T, Toya N, et al. Impact of bifidobacterium adolescentis in patients with abdominal aortic aneurysm: a cross-sectional study[J]. Biosci Microbiota Food Health, 2023, 42(1): 81-86.
12. Nakayama K, Furuyama T, Matsubara Y, et al. Gut dysbiosis and bacterial translocation in the aneurysmal wall and blood in patients with abdominal aortic aneurysm[J/OL]. PLoS One, 2022, 17(12): e0278995. DOI: 10.1371/journal.pone.0278995.
13. Nemes-Nikodém é, Gyurok GP, Dunai ZA, et al. Relationship between gut, blood, aneurysm wall and thrombus microbiome in abdominal aortic aneurysm patients[J]. Int J Mol Sci, 2024, 25(16): 8844.
14. Xie J, Lu W, Zhong L, et al. Alterations in gut microbiota of abdominal aortic aneurysm mice[J]. BMC Cardiovasc Disord, 2020, 20(1): 32.
15. He X, Bai Y, Zhou H, et al. Akkermansia muciniphila alters gut microbiota and immune system to improve cardiovascular diseases in murine model[J]. Front Microbiol, 2022, 13: 906920.
16. Li C, Liu Z, Yang S, et al. Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study[J]. Clin Exp Hypertens, 2024, 46(1): 2390419.
17. Qiu Y, Hou Y, Wei X, et al. Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study[J]. Front Microbiol, 2024, 15: 1267888.
18. Lv Y, Shen D, Zhang G, et al. Causal associations between the gut microbiome and aortic aneurysm: a Mendelian randomization study[J]. Cardiovasc Innov Appl, 2024, 9(1): 956.
19. Zhou X, Ruan W, Wang T, et al. Exploring the impact of gut microbiota on abdominal aortic aneurysm risk through a bidirectional Mendelian randomization analysis[J]. J Vasc Surg, 2024, 79(4): 763-775.
20. Jiang F, Cai M, Peng Y, et al. Changes in the gut microbiome of patients with type a aortic dissection[J]. Front Microbiol, 2023, 14: 1092360.
21. Huang S, Gao S, Shao Y, et al. Gut microbial metabolite trimethylamine N-oxide induces aortic dissection[J]. J Mol Cell Cardiol, 2024, 189: 25-37.
22. Yesitayi G, Wang Q, Wang M, et al. LPS-LBP complex induced endothelial cell pyroptosis in aortic dissection is associated with gut dysbiosis[J]. Microbes Infect, 2024, 105406.
23. Sun Y, Dong H, Sun C, et al. Investigating the association between gut microbiome and aortic aneurysm diseases: a bidirectional two-sample Mendelian randomization analysis[J]. Front Cell Infect Microbiol, 2024, 14: 1406845.
24. Li D, Li F, Jin J et al. Unraveling the causal nexus: exploring the relationship between gut microbiota and aortic dissection[PP/OL]. Res Square (2023-08-31) [2024-11-01], 2023.
25. Manabe Y, Ishibashi T, Asano R, et al. Gut dysbiosis is associated with aortic aneurysm formation and progression in Takayasu arteritis[J]. Arthritis Res Ther, 2023, 25(1): 46.
26. Witkowski M, Witkowski M, Friebel J, et al. Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis[J]. Cardiovasc Res, 2022, 118(10): 2367-2384.
27. Wang Q, Yesitayi G, Liu B, et al. Targeting metabolism in aortic aneurysm and dissection: from basic research to clinical applications[J]. Int J Biol Sci, 2023, 19(12): 3869-3891.
28. Salhi L, Rijkschroeff P, Van Hede D, et al. Blood biomarkers and serologic immunological profiles related to periodontitis in abdominal aortic aneurysm patients[J]. front cell infect microbiol, 2022, 11: 766462.
29. Ramprasath T, Han YM, Zhang D, et al. Tryptophan catabolism and inflammation: a novel therapeutic target for aortic diseases[J]. Front Immunol, 2021, 12: 731701.
30. Wang Q, Lv H, Ainiwan M, et al. Untargeted metabolomics identifies indole-3-propionic acid to relieve Ang Ⅱ-induced endothelial dysfunction in aortic dissection[J]. Mol Cell Biochem, 2024, 479(7): 1767-1786.
31. Huang SS, Liu R, Chang S, et al. Gut microbiota-derived tryptophan metabolite indole-3-aldehyde ameliorates aortic dissection[J]. Nutrients, 2023, 15(19): 4150.
32. den Besten G, van Eunen K, Groen AK, et al. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism[J]. J Lipid Res, 2013, 54(9): 2325-2340.
33. Yang F, Xia N, Guo S, et al. Propionate alleviates abdominal aortic aneurysm by modulating colonic regulatory T-cell expansion and recirculation[J]. JACC Basic Transl Sci, 2022, 7(9): 934-947.
34. Forte A, Grossi M, Bancone C, et al. Polyamine concentration is increased in thoracic ascending aorta of patients with bicuspid aortic valve[J]. Heart Vessels, 2018, 33(3): 327-339.
35. Forte A, Balistreri CR, De Feo M, et al. Polyamines and microbiota in bicuspid and tricuspid aortic valve aortopathy[J]. J Mol Cell Cardiol, 2019, 129: 179-187.

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