THE ROLE OF GUT MICROBIOME IN PREVENTION AND DEVELOPMENT OF ATHEROSCLEROSIS
Abstract
Introduction and Purpose. The gut microbiome has been the focus of scientific attention for many years. Modification of its composition are used in the prevention and treatment of many diseases. The aim of this review is to summarise the current knowledge about the role of the gut microbiome in cardiovascular diseases, using atherosclerosis as an example.
Materials and methods. A literature review was carried out using the professional PubMed database. Articles were searched using keywords such as: "gut microbiome", "atherosclerosis", "diet", "physical activity".
State of knowledge. The review describes the mechanism linking the gut microbiome to atherosclerosis and the differences in the composition of the gut microbiota in people with atherosclerosis risk factors compared with healthy individuals. The effect of probiotics on atherosclerotic lesions and the role of appropriate donor selection in faecal microbiota transplantation (FMT) are discussed. The review describes also how the composition of the gut microbiome affects physical performance.
Summary. The gut microbiome plays a huge role in the human body. It affects the health of the entire body including the cardiovascular system. The composition of the intestinal microbiota varies between individuals. It has been found that the microbiome of people with risk factors for atherosclerosis is dominated by pro-inflammatory bacteria. The possibility of modifying the composition of the microbiome through diet, physical activity and the use of probiotics offers hope for the contribution of the gut microbiota to the prevention and treatment of atherosclerosis.
References
Zhai T, Wang P, Hu X, Zheng L. Probiotics Bring New Hope for Atherosclerosis Prevention and Treatment. Oxid Med Cell Longev. 2022 Sep 24;2022:3900835. doi: 10.1155/2022/3900835.
Fan J, Watanabe T. Atherosclerosis: Known and unknown. Pathol Int. 2022 Mar;72(3):151-160. doi: 10.1111/pin.13202. Epub 2022 Jan 25.
Sanchez-Rodriguez E, Egea-Zorrilla A, Plaza-Díaz J, Aragón-Vela J, Muñoz-Quezada S, Tercedor-Sánchez L, Abadia-Molina F. The Gut Microbiota and Its Implication in the Development of Atherosclerosis and Related Cardiovascular Diseases. Nutrients. 2020 Feb 26;12(3):605. doi: 10.3390/nu12030605.
Kim SK, Guevarra RB, Kim YT, Kwon J, Kim H, Cho JH, Kim HB, Lee JH. Role of Probiotics in Human Gut Microbiome-Associated Diseases. J Microbiol Biotechnol. 2019 Sep 28;29(9):1335-1340. doi: 10.4014/jmb.1906.06064.
Tang WH, Kitai T, Hazen SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017 Mar 31;120(7):1183-1196. doi: 10.1161/CIRCRESAHA.117.309715.
Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med. 2016 Jul 7;22(7):713-22. doi: 10.1038/nm.4142.
Tang WHW, Li DY, Hazen SL. Dietary metabolism, the gut microbiome, and heart failure. Nat Rev Cardiol. 2019 Mar;16(3):137-154. doi: 10.1038/s41569-018-0108-7.
Stubbs JR, House JA, Ocque AJ, Zhang S, Johnson C, Kimber C, Schmidt K, Gupta A, Wetmore JB, Nolin TD, Spertus JA, Yu AS. Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden. J Am Soc Nephrol. 2016 Jan;27(1):305-13. doi: 10.1681/ASN.2014111063.
Chen K, Zheng X, Feng M, Li D, Zhang H. Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide Contributes to Cardiac Dysfunction in Western Diet-Induced Obese Mice. Front Physiol. 2017 Mar 21;8:139. doi: 10.3389/fphys.2017.00139.
Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, Li L, Fu X, Wu Y, Mehrabian M, Sartor RB, McIntyre TM, Silverstein RL, Tang WHW, DiDonato JA, Brown JM, Lusis AJ, Hazen SL. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell. 2016 Mar 24;165(1):111-124. doi: 10.1016/j.cell.2016.02.011.
Tang WH, Kitai T, Hazen SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017 Mar 31;120(7):1183-1196. doi: 10.1161/CIRCRESAHA.117.309715.
Jie Z, Xia H, Zhong SL, Feng Q, Li S, Liang S, Zhong H, Liu Z, Gao Y, Zhao H, Zhang D, Su Z, Fang Z, Lan Z, Li J, Xiao L, Li J, Li R, Li X, Li F, Ren H, Huang Y, Peng Y, Li G, Wen B, Dong B, Chen JY, Geng QS, Zhang ZW, Yang H, Wang J, Wang J, Zhang X, Madsen L, Brix S, Ning G, Xu X, Liu X, Hou Y, Jia H, He K, Kristiansen K. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017 Oct 10;8(1):845. doi: 10.1038/s41467-017-00900-1.
Emoto T, Yamashita T, Sasaki N, Hirota Y, Hayashi T, So A, Kasahara K, Yodoi K, Matsumoto T, Mizoguchi T, Ogawa W, Hirata K. Analysis of Gut Microbiota in Coronary Artery Disease Patients: a Possible Link between Gut Microbiota and Coronary Artery Disease. J Atheroscler Thromb. 2016 Aug 1;23(8):908-21. doi: 10.5551/jat.32672.
Vourakis M, Mayer G, Rousseau G. The Role of Gut Microbiota on Cholesterol Metabolism in Atherosclerosis. Int J Mol Sci. 2021 Jul 28;22(15):8074. doi: 10.3390/ijms22158074.
Lam V, Su J, Hsu A, Gross GJ, Salzman NH, Baker JE. Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction in Rats. PLoS One. 2016 Aug 9;11(8):e0160840. doi: 10.1371/journal.pone.0160840.
Mitra S, Drautz-Moses DI, Alhede M, Maw MT, Liu Y, Purbojati RW, Yap ZH, Kushwaha KK, Gheorghe AG, Bjarnsholt T, Hansen GM, Sillesen HH, Hougen HP, Hansen PR, Yang L, Tolker-Nielsen T, Schuster SC, Givskov M. In silico analyses of metagenomes from human atherosclerotic plaque samples. Microbiome. 2015 Sep 3;3:38. doi: 10.1186/s40168-015-0100-y.
Malik M, Suboc TM, Tyagi S, Salzman N, Wang J, Ying R, Tanner MJ, Kakarla M, Baker JE, Widlansky ME. Lactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery Disease. Circ Res. 2018 Oct 12;123(9):1091-1102. doi: 10.1161/CIRCRESAHA.118.313565.
Boets E, Gomand SV, Deroover L, Preston T, Vermeulen K, De Preter V, Hamer HM, Van den Mooter G, De Vuyst L, Courtin CM, Annaert P, Delcour JA, Verbeke KA. Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study. J Physiol. 2017 Jan 15;595(2):541-555. doi: 10.1113/JP272613.
Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, Harmsen HJM, Faber KN, Hermoso MA. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front Immunol. 2019 Mar 11;10:277. doi: 10.3389/fimmu.2019.00277. Erratum in: Front Immunol. 2019 Jun 28;10:1486. doi: 10.3389/fimmu.2019.01486.
de la Cuesta-Zuluaga J, Mueller NT, Álvarez-Quintero R, Velásquez-Mejía EP, Sierra JA, Corrales-Agudelo V, Carmona JA, Abad JM, Escobar JS. Higher Fecal Short-Chain Fatty Acid Levels Are Associated with Gut Microbiome Dysbiosis, Obesity, Hypertension and Cardiometabolic Disease Risk Factors. Nutrients. 2018 Dec 27;11(1):51. doi: 10.3390/nu11010051.
Verhaar BJH, Prodan A, Nieuwdorp M, Muller M. Gut Microbiota in Hypertension and Atherosclerosis: A Review. Nutrients. 2020 Sep 29;12(10):2982. doi: 10.3390/nu12102982.
Yan Q, Gu Y, Li X, Yang W, Jia L, Chen C, Han X, Huang Y, Zhao L, Li P, Fang Z, Zhou J, Guan X, Ding Y, Wang S, Khan M, Xin Y, Li S, Ma Y. Alterations of the Gut Microbiome in Hypertension. Front Cell Infect Microbiol. 2017 Aug 24;7:381. doi: 10.3389/fcimb.2017.00381.
Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, Haase S, Mähler A, Balogh A, Markó L, Vvedenskaya O, Kleiner FH, Tsvetkov D, Klug L, Costea PI, Sunagawa S, Maier L, Rakova N, Schatz V, Neubert P, Frätzer C, Krannich A, Gollasch M, Grohme DA, Côrte-Real BF, Gerlach RG, Basic M, Typas A, Wu C, Titze JM, Jantsch J, Boschmann M, Dechend R, Kleinewietfeld M, Kempa S, Bork P, Linker RA, Alm EJ, Müller DN. Salt-responsive gut commensal modulates TH17 axis and disease. Nature. 2017 Nov 30;551(7682):585-589. doi: 10.1038/nature24628.
Thingholm LB, Rühlemann MC, Koch M, Fuqua B, Laucke G, Boehm R, Bang C, Franzosa EA, Hübenthal M, Rahnavard A, Frost F, Lloyd-Price J, Schirmer M, Lusis AJ, Vulpe CD, Lerch MM, Homuth G, Kacprowski T, Schmidt CO, Nöthlings U, Karlsen TH, Lieb W, Laudes M, Franke A, Huttenhower C. Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition. Cell Host Microbe. 2019 Aug 14;26(2):252-264.e10. doi: 10.1016/j.chom.2019.07.004.
Lau LHS, Wong SH. Microbiota, Obesity and NAFLD. Adv Exp Med Biol. 2018;1061:111-125. doi: 10.1007/978-981-10-8684-7_9.
Liu H, Du T, Li C, Yang G. STAT3 phosphorylation in central leptin resistance. Nutr Metab (Lond). 2021 Apr 13;18(1):39. doi: 10.1186/s12986-021-00569-w.
Ahmed H, Leyrolle Q, Koistinen V, Kärkkäinen O, Layé S, Delzenne N, Hanhineva K. Microbiota-derived metabolites as drivers of gut-brain communication. Gut Microbes. 2022 Jan-Dec;14(1):2102878. doi: 10.1080/19490976.2022.2102878.
Cheng YC, Liu JR. Effect of Lactobacillus rhamnosus GG on Energy Metabolism, Leptin Resistance, and Gut Microbiota in Mice with Diet-Induced Obesity. Nutrients. 2020 Aug 24;12(9):2557. doi: 10.3390/nu12092557.
Kriaa A, Bourgin M, Potiron A, Mkaouar H, Jablaoui A, Gérard P, Maguin E, Rhimi M. Microbial impact on cholesterol and bile acid metabolism: current status and future prospects. J Lipid Res. 2019 Feb;60(2):323-332. doi: 10.1194/jlr.R088989.
Tang WH, Kitai T, Hazen SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017 Mar 31;120(7):1183-1196. doi: 10.1161/CIRCRESAHA.117.309715.
Villette R, Kc P, Beliard S, Salas Tapia MF, Rainteau D, Guerin M, Lesnik P. Unraveling Host-Gut Microbiota Dialogue and Its Impact on Cholesterol Levels. Front Pharmacol. 2020 Apr 3;11:278. doi: 10.3389/fphar.2020.00278.
Li DY, Li XS, Chaikijurajai T, Li L, Wang Z, Hazen SL, Tang WHW. Relation of Statin Use to Gut Microbial Trimethylamine N-Oxide and Cardiovascular Risk. Am J Cardiol. 2022 Sep 1;178:26-34. doi: 10.1016/j.amjcard.2022.05.010.
Sun B, Li L, Zhou X. Comparative analysis of the gut microbiota in distinct statin response patients in East China. J Microbiol. 2018 Dec;56(12):886-892. doi: 10.1007/s12275-018-8152-x.
Kummen M, Solberg OG, Storm-Larsen C, Holm K, Ragnarsson A, Trøseid M, Vestad B, Skårdal R, Yndestad A, Ueland T, Svardal A, Berge RK, Seljeflot I, Gullestad L, Karlsen TH, Aaberge L, Aukrust P, Hov JR. Rosuvastatin alters the genetic composition of the human gut microbiome. Sci Rep. 2020 Mar 25;10(1):5397. doi: 10.1038/s41598-020-62261-y.
Khan TJ, Ahmed YM, Zamzami MA, Siddiqui AM, Khan I, Baothman OAS, Mehanna MG, Kuerban A, Kaleemuddin M, Yasir M. Atorvastatin Treatment Modulates the Gut Microbiota of the Hypercholesterolemic Patients. OMICS. 2018 Feb;22(2):154-163. doi: 10.1089/omi.2017.0130.
Ekblom-Bak E, Börjesson M, Ekblom Ö, Angerås O, Bergman F, Berntsson C, Carlhäll CJ, Engström G, Engvall J, Fagman E, Flinck A, Johansson P, Jujic A, Kero T, Lind L, Mannila M, Ostenfeld E, Persson A, Persson J, Persson M, Redfors B, Sandberg C, Wennberg P, Öhlin J, Östgren CJ, Jernberg T. Accelerometer derived physical activity and subclinical coronary and carotid atherosclerosis: cross-sectional analyses in 22 703 middle-aged men and women in the SCAPIS study. BMJ Open. 2023 Nov 23;13(11):e073380. doi: 10.1136/bmjopen-2023-073380.
Ji H, Gulati M, Huang TY, Kwan AC, Ouyang D, Ebinger JE, Casaletto K, Moreau KL, Skali H, Cheng S. Sex Differences in Association of Physical Activity With All-Cause and Cardiovascular Mortality. J Am Coll Cardiol. 2024 Feb 27;83(8):783-793. doi: 10.1016/j.jacc.2023.12.019.
Sawyer BJ, Tucker WJ, Bhammar DM, Ryder JR, Sweazea KL, Gaesser GA. Effects of high-intensity interval training and moderate-intensity continuous training on endothelial function and cardiometabolic risk markers in obese adults. J Appl Physiol (1985). 2016 Jul 1;121(1):279-88. doi: 10.1152/japplphysiol.00024.2016.
Boutcher YN, Boutcher SH. Exercise intensity and hypertension: what's new? J Hum Hypertens. 2017 Mar;31(3):157-164. doi: 10.1038/jhh.2016.62.
Marttinen M, Ala-Jaakkola R, Laitila A, Lehtinen MJ. Gut Microbiota, Probiotics and Physical Performance in Athletes and Physically Active Individuals. Nutrients. 2020 Sep 25;12(10):2936. doi: 10.3390/nu12102936.
Petersen LM, Bautista EJ, Nguyen H, Hanson BM, Chen L, Lek SH, Sodergren E, Weinstock GM. Community characteristics of the gut microbiomes of competitive cyclists. Microbiome. 2017 Aug 10;5(1):98. doi: 10.1186/s40168-017-0320-4.
Barton W, Penney NC, Cronin O, Garcia-Perez I, Molloy MG, Holmes E, Shanahan F, Cotter PD, O'Sullivan O. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut. 2018 Apr;67(4):625-633. doi: 10.1136/gutjnl-2016-313627.
LeBlanc JG, Chain F, Martín R, Bermúdez-Humarán LG, Courau S, Langella P. Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb Cell Fact. 2017 May 8;16(1):79. doi: 10.1186/s12934-017-0691-z.
Scheiman J, Luber JM, Chavkin TA, MacDonald T, Tung A, Pham LD, Wibowo MC, Wurth RC, Punthambaker S, Tierney BT, Yang Z, Hattab MW, Avila-Pacheco J, Clish CB, Lessard S, Church GM, Kostic AD. Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nat Med. 2019 Jul;25(7):1104-1109. doi: 10.1038/s41591-019-0485-4.
Diab A, Dastmalchi LN, Gulati M, Michos ED. A Heart-Healthy Diet for Cardiovascular Disease Prevention: Where Are We Now? Vasc Health Risk Manag. 2023 Apr 21;19:237-253. doi: 10.2147/VHRM.S379874.
Abrignani V, Salvo A, Pacinella G, Tuttolomondo A. The Mediterranean Diet, Its Microbiome Connections, and Cardiovascular Health: A Narrative Review. Int J Mol Sci. 2024 Apr 30;25(9):4942. doi: 10.3390/ijms25094942.
Diao Z, Molludi J, Latef Fateh H, Moradi S. Comparison of the low-calorie DASH diet and a low-calorie diet on serum TMAO concentrations and gut microbiota composition of adults with overweight/obesity: a randomized control trial. Int J Food Sci Nutr. 2024 Mar;75(2):207-220. doi: 10.1080/09637486.2023.2294685.
Tomova A, Bukovsky I, Rembert E, Yonas W, Alwarith J, Barnard ND, Kahleova H. The Effects of Vegetarian and Vegan Diets on Gut Microbiota. Front Nutr. 2019 Apr 17;6:47. doi: 10.3389/fnut.2019.00047.
Geng J, Ni Q, Sun W, Li L, Feng X. The links between gut microbiota and obesity and obesity related diseases. Biomed Pharmacother. 2022 Mar;147:112678. doi: 10.1016/j.biopha.2022.112678.
Gérard P. Gut microbiota and obesity. Cell Mol Life Sci. 2016 Jan;73(1):147-62. doi: 10.1007/s00018-015-2061-5.
Farias D.P., Araújo F.F., Neri-Numa I.A., Pastore G.M. Prebiotics: Trends in food, health and technological applications. Trends Food Sci. Technol. 2019;93:23–35. doi: 10.1016/j.tifs.2019.09.004.
Zhao, W., Liu, Y., Latta, M., Ma, W., Wu, Z., & Chen, P. (2019). Probiotics database: a potential source of fermented foods. International Journal of Food Properties, 22(1), 198–217. https://doi.org/10.1080/10942912.2019.1579737.
Wang L, Guo MJ, Gao Q, Yang JF, Yang L, Pang XL, Jiang XJ. The effects of probiotics on total cholesterol: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018 Feb;97(5):e9679. doi: 10.1097/MD.0000000000009679.
Wu Y, Zhang Q, Ren Y, Ruan Z. Effect of probiotic Lactobacillus on lipid profile: A systematic review and meta-analysis of randomized, controlled trials. PLoS One. 2017 Jun 8;12(6):e0178868. doi: 10.1371/journal.pone.0178868.
El Hage R, Al-Arawe N, Hinterseher I. The Role of the Gut Microbiome and Trimethylamine Oxide in Atherosclerosis and Age-Related Disease. Int J Mol Sci. 2023 Jan 25;24(3):2399. doi: 10.3390/ijms24032399.
Chan YK, El-Nezami H, Chen Y, Kinnunen K, Kirjavainen PV. Probiotic mixture VSL#3 reduce high fat diet induced vascular inflammation and atherosclerosis in ApoE(-/-) mice. AMB Express. 2016 Dec;6(1):61. doi: 10.1186/s13568-016-0229-5.
Wilson BC, Vatanen T, Cutfield WS, O'Sullivan JM. The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Front Cell Infect Microbiol. 2019 Jan 21;9:2. doi: 10.3389/fcimb.2019.00002.
Chehoud C, Dryga A, Hwang Y, Nagy-Szakal D, Hollister EB, Luna RA, Versalovic J, Kellermayer R, Bushman FD. Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation. mBio. 2016 Mar 29;7(2):e00322. doi: 10.1128/mBio.00322-16.
Kootte RS, Levin E, Salojärvi J, Smits LP, Hartstra AV, Udayappan SD, Hermes G, Bouter KE, Koopen AM, Holst JJ, Knop FK, Blaak EE, Zhao J, Smidt H, Harms AC, Hankemeijer T, Bergman JJGHM, Romijn HA, Schaap FG, Olde Damink SWM, Ackermans MT, Dallinga-Thie GM, Zoetendal E, de Vos WM, Serlie MJ, Stroes ESG, Groen AK, Nieuwdorp M. Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition. Cell Metab. 2017 Oct 3;26(4):611-619.e6. doi: 10.1016/j.cmet.2017.09.008.
Chen AT, Zhang J, Zhang Y. Gut microbiota in heart failure and related interventions. Imeta. 2023 Jul 10;2(3):e125. doi: 10.1002/imt2.125.
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