The role of the gut microbiome in cardiovascular disease
DOI:
https://doi.org/10.12775/JEHS.2025.82.60447Keywords
gut microbiota, cardiovascular disease, TMAO, SCFA, LPS, dysbiosisAbstract
In recent years, the gut microbiome has gained increasing recognition as a crucial modulator of physiological homeostasis, including cardiovascular function. Numerous studies indicate that disruptions in the composition and activity of intestinal microbiota—referred to as dysbiosis—may significantly contribute to the onset and progression of cardiovascular diseases, including atherosclerosis, hypertension, heart failure, and arrhythmias. Particular attention has been paid to microbial metabolites such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and lipopolysaccharides (LPS), which exert significant effects on inflammatory, immunological, and metabolic pathways.
The aim of this review was to synthesize current evidence regarding the association between the gut microbiota and the pathogenesis of cardiovascular disorders, emphasizing potential molecular mechanisms and therapeutic opportunities arising from microbiome modulation. Additionally, environmental, dietary, and pharmacological factors influencing microbiota composition and their implications for cardiovascular risk were discussed.
Accumulated evidence suggests the gut microbiome could serve both as a biomarker of cardiovascular risk and as a potential therapeutic target within personalized medicine frameworks. However, further clinical research is required to precisely define its role in the pathogenesis and treatment of cardiovascular diseases.
References
[1] E. Sanchez-Rodriguez et al., ‘The gut microbiota and its implication in the development of atherosclerosis and related cardiovascular diseases’, Mar. 01, 2020, MDPI AG. doi: 10.3390/nu12030605.
[2] Y. Li, G. Cao, W. Jing, J. Liu, and M. Liu, ‘Global trends and regional differences in incidence and mortality of cardiovascular disease, 1990−2019: findings from 2019 global burden of disease study’, Eur J Prev Cardiol, vol. 30, no. 3, pp. 276–286, Feb. 2023, doi: 10.1093/eurjpc/zwac285.
[3] W. H. W. Tang, T. Kitai, and S. L. Hazen, ‘Gut Microbiota in Cardiovascular Health and Disease’, Circ Res, vol. 120, no. 7, pp. 1183–1196, Mar. 2017, doi:
10.1161/CIRCRESAHA.117.309715.
[4] J. Qin et al., ‘A metagenome-wide association study of gut microbiota in type 2 diabetes’, Nature, vol. 490, no. 7418, pp. 55–60, Oct. 2012, doi:
10.1038/nature11450.
[5] E. Le Chatelier et al., ‘Richness of human gut microbiome correlates with metabolic markers’, Nature, vol. 500, no. 7464, pp. 541–546, Aug. 2013, doi:
10.1038/nature12506.
[6] F. H. Karlsson et al., ‘Symptomatic atherosclerosis is associated with an altered gut metagenome’, Nat Commun, vol. 3, 2012, doi: 10.1038/ncomms2266.
[7] A. Sandek et al., ‘Intestinal Blood Flow in Patients With Chronic Heart Failure A Link With Bacterial Growth, Gastrointestinal Symptoms, and Cachexia’, 2014. doi:
10.1016/j.jacc.2014.06.1179.
[8] E. Pasini et al., ‘Pathogenic Gut Flora in Patients With Chronic Heart Failure’, 2016. doi: 10.1016/j.jchf.2015.10.009.
[9] A. Luqman et al., ‘Role of the intestinal microbiome and its therapeutic intervention in cardiovascular disorder’, Front Immunol, vol. 15, Jan. 2024, doi:
10.3389/fimmu.2024.1321395.
[10] A. M. Carías Domínguez, D. de Jesús Rosa Salazar, J. P. Stefanolo, M. C. Cruz Serrano, I. C. Casas, and J. R. Zuluaga Peña, ‘Intestinal Dysbiosis: Exploring Definition,
Associated Symptoms, and Perspectives for a Comprehensive Understanding — a Scoping Review’, Feb. 01, 2024, Springer. doi: 10.1007/s12602-024-10353-w.
[11] B. K. Perler, E. S. Friedman, and G. D. Wu, ‘The Role of the Gut Microbiota in the Relationship Between Diet and Human Health’, Annual Review of Physiology Downloaded from www.annualreviews.org. Guest, 2025, doi: 10.1146/annurevphysiol-031522.
[12] G. P. Donaldson, S. M. Lee, and S. K. Mazmanian, ‘Gut biogeography of the bacterial microbiota’, Dec. 16, 2015, Nature Publishing Group. doi: 10.1038/nrmicro3552.
[13] F. Di Vincenzo, A. Del Gaudio, V. Petito, L. R. Lopetuso, and F. Scaldaferri, ‘Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review’, Mar. 01, 2024, Springer Science and Business Media Deutschland GmbH. doi:
10.1007/s11739-023-03374-w.
[14] X. Chen et al., ‘Gut microbiota and microbiota-derived metabolites in cardiovascular diseases’, Oct. 05, 2023, Lippincott Williams and Wilkins. doi:
10.1097/CM9.0000000000002206.
[15] K. M. Ng et al., ‘Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens’, Nature, vol. 502, no. 7469, pp. 96–99, 2013, doi:
10.1038/nature12503.
[16] S. M. Huse, L. Dethlefsen, J. A. Huber, D. M. Welch, D. A. Relman, and M. L. Sogin, ‘Exploring microbial diversity and taxonomy using SSU rRNA hypervariable tag sequencing’, PLoS Genet, vol. 4, no. 11, Nov. 2008, doi:
10.1371/journal.pgen.1000255.
[17] L. Trasande, J. Blustein, M. Liu, E. Corwin, L. M. Cox, and M. J. Blaser, ‘Infant antibiotic exposures and early-life body mass’, Int J Obes, vol. 37, no. 1, pp. 16–23, Jan. 2013, doi: 10.1038/ijo.2012.132.
[18] J. P. Karl et al., ‘Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress’, American Journal of Physiology-Gastrointestinal and Liver Physiology, vol. 312, no. 6, pp. G559–G571, Jun. 2017, doi: 10.1152/ajpgi.00066.2017.
[19] M. D. Cook et al., ‘Exercise and gut immune function: evidence of alterations in colon immune cell homeostasis and microbiome characteristics with exercise training’, Immunol Cell Biol, vol. 94, no. 2, pp. 158–163, Feb. 2016, doi: 10.1038/icb.2015.108.
[20] S. J. Song et al., ‘Cohabiting family members share microbiota with one another and with their dogs’, Elife, vol. 2013, no. 2, Apr. 2013, doi: 10.7554/eLife.00458.
[21] J. Zhu, J. Lyu, R. Zhao, G. Liu, and S. Wang, ‘Gut macrobiotic and its metabolic pathways modulate cardiovascular disease’, 2023, Frontiers Media SA. doi:
10.3389/fmicb.2023.1272479.
[22] M. Canyelles, C. Borràs, N. Rotllan, M. Tondo, J. C. Escolà-Gil, and F. Blanco-Vaca, ‘Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease?’, Feb. 01, 2023, MDPI. doi: 10.3390/ijms24031940.
[23] J. M. Brown and S. L. Hazen, ‘Microbial modulation of cardiovascular disease’, Feb.
12, 2018, Nature Publishing Group. doi: 10.1038/nrmicro.2017.149.
[24] B. J. Bennett et al., ‘Trimethylamine-N-Oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation’, Cell Metab, vol. 17, no. 1, pp. 49–60, Jan. 2013, doi: 10.1016/j.cmet.2012.12.011.
[25] K. A. Romano, E. I. Vivas, D. Amador-Noguez, and F. E. Rey, ‘Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide’, mBio, vol. 6, no. 2, Mar. 2015, doi: 10.1128/mBio.02481-14.
[26] M. H. Janeiro, M. J. Ramírez, F. I. Milagro, J. A. Martínez, and M. Solas, ‘Implication of trimethylamine n-oxide (TMAO) in disease: Potential biomarker or new therapeutic target’, Oct. 01, 2018, MDPI AG. doi: 10.3390/nu10101398.
[27] D. Mafra et al., ‘Red meat intake in chronic kidney disease patients: Two sides of the coin’, Nutrition, vol. 46, pp. 26–32, Feb. 2018, doi: 10.1016/j.nut.2017.08.015.
[28] W. Zhu, Z. Wang, W. H. W. Tang, and S. L. Hazen, ‘Gut microbe-generated trimethylamine N-oxide from dietary choline is prothrombotic in subjects’, Apr. 25, 2017, Lippincott Williams and Wilkins. doi: 10.1161/CIRCULATIONAHA.116.025338.
[29] N. B. B. S. L. X. S. L. S. C. X. J. R. A. K. L. L. Y. W. H. W. T. R. M. K. and S. L. H. A. Zeneng Wang, ‘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’, Feb. 14, 2019, Oxford University Press. doi: 10.1093/eurheartj/ehy905.
[30] J. Geng et al., ‘Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway’, Biomedicine & Pharmacotherapy, vol. 97, pp. 941–947, Jan. 2018, doi: 10.1016/j.biopha.2017.11.016.
[31] E. Randrianarisoa et al., ‘Relationship of serum trimethylamine N-oxide (TMAO) levels with early atherosclerosis in humans’, Sci Rep, vol. 6, May 2016, doi:
10.1038/srep26745.
[32] J. R. Stubbs et al., ‘Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden’, Journal of the American Society of Nephrology, vol. 27, no. 1, pp. 305–313, Jan. 2016, doi: 10.1681/ASN.2014111063.
[33] J. Gao et al., ‘Gut microbial taxa as potential predictive biomarkers for acute coronary syndrome and post-STEMI cardiovascular events’, Sci Rep, vol. 10, no. 1, Dec. 2020, doi: 10.1038/s41598-020-59235-5.
[34] G. G. Schiattarella et al., ‘Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response metaanalysis’, Eur Heart J, vol. 38, no. 39, pp. 2948–2956, Oct. 2017, doi:
10.1093/eurheartj/ehx342.
[35] M. Amrein et al., ‘Gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and cardiovascular risk in patients with suspected functionally relevant coronary artery disease (fCAD)’, Clinical Research in Cardiology, vol. 111, no. 6, pp.
692–704, Jun. 2022, doi: 10.1007/s00392-022-01992-6.
[36] C. Roncal et al., ‘Trimethylamine-N-Oxide (TMAO) Predicts Cardiovascular Mortality in Peripheral Artery Disease’, Sci Rep, vol. 9, no. 1, Dec. 2019, doi: 10.1038/s41598-01952082-z.
[37] W. Zhu et al., ‘Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk’, Cell, vol. 165, no. 1, pp. 111–124, Mar. 2016, doi:
10.1016/j.cell.2016.02.011.
[38] A. B. Roberts et al., ‘Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential’, Nat Med, vol. 24, no. 9, pp. 1407–1417, Sep. 2018, doi:
10.1038/s41591-018-0128-1.
[39] D. J. Morrison and T. Preston, ‘Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism’, May 03, 2016, Taylor and Francis Inc. doi: 10.1080/19490976.2015.1134082.
[40] V. Gerdes, M. Gueimonde, L. Pajunen, M. Nieuwdorp, and K. Laitinen, ‘How strong is the evidence that gut microbiota composition can be influenced by lifestyle interventions in a cardio-protective way?’, Atherosclerosis, vol. 311, pp. 124–142, Oct. 2020, doi: 10.1016/j.atherosclerosis.2020.08.028.
[41] Y. Wu, H. Xu, X. Tu, and Z. Gao, ‘The Role of Short-Chain Fatty Acids of Gut Microbiota Origin in Hypertension’, Sep. 28, 2021, Frontiers Media S.A. doi:
10.3389/fmicb.2021.730809.
[42] J. L. Pluznick et al., ‘Olfactory receptor responding to gut microbiotaderived signals plays a role in renin secretion and blood pressure regulation’, Proc Natl Acad Sci U S A, vol. 110, no. 11, pp. 4410–4415, Mar. 2013, doi: 10.1073/pnas.1215927110.
[43] N. Natarajan et al., ‘Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41’, Physiol Genomics, vol. 48, pp. 826– 834, 2016, doi: 10.1152/physiolgenomics.00089.2016.-Short.
[44] J. Li et al., ‘Gut microbiota dysbiosis contributes to the development of hypertension’, Microbiome, vol. 5, no. 1, 2017, doi: 10.1186/s40168-016-0222-x.
[45] R. F. Maldonado, I. Sá-Correia, and M. A. Valvano, ‘Lipopolysaccharide modification in gram-negative bacteria during chronic infection’, Jul. 01, 2016, Oxford University Press. doi: 10.1093/femsre/fuw007.
[46] S. Cao et al., ‘LPS challenge increased intestinal permeability, disrupted mitochondrial function and triggered mitophagy of piglets’, Innate Immun, vol. 24, no. 4, pp. 221– 230, May 2018, doi: 10.1177/1753425918769372.
[47] S. Nooti et al., ‘Oxidized Low-density Lipoproteins and Lipopolysaccharides Augment Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine’, Cardiol Cardiovasc Med, vol. 07, no. 04, 2023, doi: 10.26502/fccm.92920338.
[48] J. E. Jaw et al., ‘Lung exposure to lipopolysaccharide causes atherosclerotic plaque destabilisation’, European Respiratory Journal, vol. 48, no. 1, pp. 205–215, Jul. 2016, doi: 10.1183/13993003.00972-2015.
[49] M. Ni et al., ‘Atherosclerotic plaque disruption induced by stress and lipopolysaccharide in apolipoprotein E knockout mice’, American Journal of Physiology-Heart and Circulatory Physiology, vol. 296, no. 5, pp. H1598–H1606, May 2009, doi: 10.1152/ajpheart.01202.2008.
[50] X. Zhou et al., ‘Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction’, Microbiome, vol. 6, no. 1, p. 66, Apr. 2018, doi: 10.1186/s40168-018-0441-4.
[51] J. Gerritsen, H. Smidt, G. T. Rijkers, and W. M. De Vos, ‘Intestinal microbiota in human health and disease: The impact of probiotics’, Aug. 2011. doi: 10.1007/s12263-0110229-7.
[52] D. M. Linares, P. Ross, and C. Stanton, ‘Beneficial Microbes: The pharmacy in the gut’, Jan. 02, 2016, Taylor and Francis Inc. doi: 10.1080/21655979.2015.1126015.
[53] A. Nowak, A. Paliwoda, and J. Błasiak, ‘Anti-proliferative, pro-apoptotic and antioxidative activity of Lactobacillus and Bifidobacterium strains: A review of
mechanisms and therapeutic perspectives’, Crit Rev Food Sci Nutr, vol. 59, no. 21, pp.
3456–3467, Nov. 2019, doi: 10.1080/10408398.2018.1494539.
[54] F. Raygan et al., ‘The effects of probiotic supplementation on metabolic status in type 2 diabetic patients with coronary heart disease IRCT2017082733941N5 IRCT’,
Diabetol Metab Syndr, vol. 10, no. 1, Jun. 2018, doi: 10.1186/s13098-018-0353-2.
[55] J. A. Parnell and R. A. Reimer, ‘Effect of prebiotic fibre supplementation on hepatic gene expression and serum lipids: A dose-response study in JCR:LA-cp rats’, British Journal of Nutrition, vol. 103, no. 11, pp. 1577–1584, Jun. 2010, doi:
10.1017/S0007114509993539.
[56] V. Mofid, A. Izadi, S. Y. Mojtahedi, and L. Khedmat, ‘Therapeutic and Nutritional Effects of Synbiotic Yogurts in Children and Adults: a Clinical Review’, Probiotics Antimicrob Proteins, vol. 12, no. 3, pp. 851–859, Sep. 2020, doi: 10.1007/s12602-01909594-x.
[57] A. Leshem, N. Horesh, and E. Elinav, ‘Fecal microbial transplantation and its potential application in cardiometabolic syndrome’, 2019, Frontiers Media S.A. doi:
10.3389/fimmu.2019.01341.
[58] J. C. Gregory et al., ‘Transmission of atherosclerosis susceptibility with gut microbial transplantation’, Journal of Biological Chemistry, vol. 290, no. 9, pp. 5647–5660, Feb. 2015, doi: 10.1074/jbc.M114.618249.
[59] L. M. De Leon, J. B. Watson, and C. R. Kelly, ‘Transient Flare of Ulcerative Colitis After Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection’, Clinical Gastroenterology and Hepatology, vol. 11, no. 8, pp. 1036–1038, Aug. 2013, doi:
10.1016/j.cgh.2013.04.045.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Mateusz Świątko, Paweł Sosnowski, Joanna Rybak, Marcin Grzebyk, Anna Tokarska, Aleksandra Arnista, Katarzyna Gawrońska, Agnieszka Waszczuk, Aleksandra Kołodziejczyk, Piotr Łapiński
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 200
Number of citations: 0
