Intestinal Flora Derived Metabolites Affect the Occurrence and Development of Cardiovascular Disease

Overview

Journal J Multidiscip Healthc

Publisher Dove Medical Press

Specialty Health Services

Date 2022 Nov 17

PMID 36388628

Authors

Yinuo Wen

Zefan Sun

Shuoyin Xie

Zixuan Hu

Qicheng Lan

Yupeng Sun

Linbo Yuan

Changlin Zhai

Affiliations

Soon will be listed here.

Abstract

In recent years, increasing evidence has shown that the gut microbiota and their metabolites play a pivotal role in human health and diseases, especially the cardiovascular diseases (CVDs). Intestinal flora imbalance (changes in the composition and function of intestinal flora) accelerates the progression of CVDs. The intestinal flora breaks down the food ingested by the host into a series of metabolically active products, including trimethylamine N-Oxide (TMAO), short-chain fatty acids (SCFAs), primary and secondary bile acids, tryptophan and indole derivatives, phenylacetylglutamine (PAGln) and branched chain amino acids (BCAA). These metabolites participate in the occurrence and development of CVDs via abnormally activating these signaling pathways more swiftly when the gut barrier integrity is broken down. This review focuses on the production and metabolism of TMAO and SCFAs. At the same time, we summarize the roles of intestinal flora metabolites in the occurrence and development of coronary heart disease and hypertension, pulmonary hypertension and other CVDs. The theories of "gut-lung axis" and "gut-heart axis" are provided, aiming to explore the potential targets for the treatment of CVDs based on the roles of the intestinal flora in the CVDs.

Citing Articles

Gut microbiota and atrial cardiomyopathy.

Sun T, Song B, Li B Front Cardiovasc Med. 2025; 12:1541278.

PMID: 39968343 PMC: 11832500. DOI: 10.3389/fcvm.2025.1541278.

Pre-procedural TMAO as a predictor for recurrence of atrial fibrillation after catheter ablation.

Meng S, Ni T, Du Q, Liu M, Ge P, Geng J BMC Cardiovasc Disord. 2024; 24(1):750.

PMID: 39732662 PMC: 11681644. DOI: 10.1186/s12872-024-04170-w.

Role of Gut Microbial Metabolites in Cardiovascular Diseases-Current Insights and the Road Ahead.

Datta S, Pasham S, Inavolu S, Boini K, Koka S Int J Mol Sci. 2024; 25(18).

PMID: 39337693 PMC: 11432476. DOI: 10.3390/ijms251810208.

Causal relationship between the gut microbiota, immune cells, and coronary heart disease: a mediated Mendelian randomization analysis.

Yang F, Song H, Tang W, Liu L, Zhu Z, Ouyang B Front Microbiol. 2024; 15:1449935.

PMID: 39161605 PMC: 11332803. DOI: 10.3389/fmicb.2024.1449935.

The Mediterranean Diet, Its Microbiome Connections, and Cardiovascular Health: A Narrative Review.

Abrignani V, Salvo A, Pacinella G, Tuttolomondo A Int J Mol Sci. 2024; 25(9).

PMID: 38732161 PMC: 11084172. DOI: 10.3390/ijms25094942.

References

DOdorico I, Di Bella S, Monticelli J, Giacobbe D, Boldock E, Luzzati R . Role of fecal microbiota transplantation in inflammatory bowel disease. J Dig Dis. 2018; 19(6):322-334. DOI: 10.1111/1751-2980.12603. View

Ufnal M, Zadlo A, Ostaszewski R . TMAO: A small molecule of great expectations. Nutrition. 2015; 31(11-12):1317-23. DOI: 10.1016/j.nut.2015.05.006. View

Song K, Li T, Owsley E, Chiang J . A putative role of micro RNA in regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes. J Lipid Res. 2010; 51(8):2223-33. PMC: 2903801. DOI: 10.1194/jlr.M004531. View

Yokota A, Fukiya S, Islam K, Ooka T, Ogura Y, Hayashi T . Is bile acid a determinant of the gut microbiota on a high-fat diet?. Gut Microbes. 2012; 3(5):455-9. DOI: 10.4161/gmic.21216. View

Duttaroy A . Role of Gut Microbiota and Their Metabolites on Atherosclerosis, Hypertension and Human Blood Platelet Function: A Review. Nutrients. 2021; 13(1). PMC: 7824497. DOI: 10.3390/nu13010144. View

Xu G, Pan L, Li H, Shang Q, Honda A, Shefer S . Dietary cholesterol stimulates CYP7A1 in rats because farnesoid X receptor is not activated. Am J Physiol Gastrointest Liver Physiol. 2003; 286(5):G730-5. DOI: 10.1152/ajpgi.00397.2003. View

Ding L, Chang M, Guo Y, Zhang L, Xue C, Yanagita T . Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism. Lipids Health Dis. 2018; 17(1):286. PMC: 6300890. DOI: 10.1186/s12944-018-0939-6. View

Gurav A, Sivaprakasam S, Bhutia Y, Boettger T, Singh N, Ganapathy V . Slc5a8, a Na+-coupled high-affinity transporter for short-chain fatty acids, is a conditional tumour suppressor in colon that protects against colitis and colon cancer under low-fibre dietary conditions. Biochem J. 2015; 469(2):267-78. PMC: 4943859. DOI: 10.1042/BJ20150242. View

Metghalchi S, Ponnuswamy P, Simon T, Haddad Y, Laurans L, Clement M . Indoleamine 2,3-Dioxygenase Fine-Tunes Immune Homeostasis in Atherosclerosis and Colitis through Repression of Interleukin-10 Production. Cell Metab. 2015; 22(3):460-71. DOI: 10.1016/j.cmet.2015.07.004. View

10.

Imazu M, Fukuda H, Kanzaki H, Amaki M, Hasegawa T, Takahama H . Plasma indoxyl sulfate levels predict cardiovascular events in patients with mild chronic heart failure. Sci Rep. 2020; 10(1):16528. PMC: 7536212. DOI: 10.1038/s41598-020-73633-9. View

11.

Nohr M, Egerod K, Christiansen S, Gille A, Offermanns S, Schwartz T . Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia. Neuroscience. 2015; 290:126-37. DOI: 10.1016/j.neuroscience.2015.01.040. View

12.

Porez G, Prawitt J, Gross B, Staels B . Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. J Lipid Res. 2012; 53(9):1723-37. PMC: 3413216. DOI: 10.1194/jlr.R024794. View

13.

Agus A, Planchais J, Sokol H . Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018; 23(6):716-724. DOI: 10.1016/j.chom.2018.05.003. View

14.

Asarat M, Apostolopoulos V, Vasiljevic T, Donkor O . Short-chain fatty acids produced by synbiotic mixtures in skim milk differentially regulate proliferation and cytokine production in peripheral blood mononuclear cells. Int J Food Sci Nutr. 2015; 66(7):755-65. DOI: 10.3109/09637486.2015.1088935. View

15.

Robles-Vera I, Toral M, Romero M, Jimenez R, Sanchez M, Perez-Vizcaino F . Antihypertensive Effects of Probiotics. Curr Hypertens Rep. 2017; 19(4):26. DOI: 10.1007/s11906-017-0723-4. View

16.

Pluznick J, Protzko R, Gevorgyan H, Peterlin Z, Sipos A, Han J . Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci U S A. 2013; 110(11):4410-5. PMC: 3600440. DOI: 10.1073/pnas.1215927110. View

17.

Roth G, Johnson C, Abajobir A, Abd-Allah F, Abera S, Abyu G . Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol. 2017; 70(1):1-25. PMC: 5491406. DOI: 10.1016/j.jacc.2017.04.052. View

18.

Tang C, Offermanns S . FFA2 and FFA3 in Metabolic Regulation. Handb Exp Pharmacol. 2016; 236:205-220. DOI: 10.1007/164_2016_50. View

19.

Wang X, Wang Y, Antony V, Sun H, Liang G . Metabolism-Associated Molecular Patterns (MAMPs). Trends Endocrinol Metab. 2020; 31(10):712-724. DOI: 10.1016/j.tem.2020.07.001. View

20.

Russell D . The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003; 72:137-74. DOI: 10.1146/annurev.biochem.72.121801.161712. View