The gastrointestinal tract and cardiovascular diseases – do they have anything in common?
DOI:
https://doi.org/10.6016/ZdravVestn.2989Keywords:
gut microbiota, dysbiosis, diagnostic methods, pathophysiological mechanisms, cardiovascular diseasesAbstract
Human gut microbiota is a collection of bacteria, archaea, fungi, viruses and parasites that inhabit the gastrointestinal tract and produce a diverse ecosystem of about 1014 microorganisms. Microbiota diversity is caused by differences in the host genome and by environmental factors such as hygiene, lifestyle, nutrition and various drugs. The results of research over the last decade have confirmed that altered gut microbiota, dysbiosis, contributes to the development of various diseases, including cardiovascular diseases, type 2 diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease (NAFLD), chronic inflammatory bowel disease and even some cancers. In the article, the authors present some recent findings on the diversity of gut microbiota, diagnostic methods and some of the pathophysiological mechanisms that influence the development of cardiovascular diseases.
Downloads
References
1. Lau K, Srivatsav V, Rizwan A, Nashed A, Liu R, Shen R, et al. Bridging the Gap between Gut Microbial Dysbiosis and Cardiovascular Diseases. Nutrients. 2017;9(8):859.
DOI: 10.3390/nu9080859
PMID: 28796176
2. Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859-904.
DOI: 10.1152/physrev.00045.2009
PMID: 20664075
3. Brown JM, Hazen SL. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annu Rev Med. 2015;66(1):343-59.
DOI: 10.1146/annurev-med-060513-093205
PMID: 25587655
4. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-63.
DOI: 10.1146/annurev-med-060513-093205
PMID: 25587655
5. Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med. 2016;22(7):713-22.
DOI: 10.1038/nm.4142
PMID: 27387886
6. Nallu A, Sharma S, Ramezani A, Muralidharan J, Raj D. Gut microbiome in chronic kidney disease: challenges and opportunities. Transl Res. 2017;179:24-37.
DOI: 10.1016/j.trsl.2016.04.007
PMID: 27187743
7. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575-84.
DOI: 10.1056/NEJMoa1109400
PMID: 23614584
8. Tang WH, Kitai T, Hazen SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017;120(7):1183-96.
DOI: 10.1161/CIRCRESAHA.117.309715
PMID: 28360349
9. Yamashiro K, Tanaka R, Urabe T, Ueno Y, Yamashiro Y, Nomoto K, et al. Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke. PLoS One. 2017;12(2):e0171521.
DOI: 10.1371/journal.pone.0171521
PMID: 28166278
10. Šket R, Prevoršek Z, Košeto D, Sebastijanović A, Konda S, Bajuk J, et al. Analitski in konceptualni izzvi pri raziskovanju človeške mikrobiote za potrebe personalizirane večnivojske medicine. Med Razgl. 2019;58(2):211-34.
11. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449(7164):804-10.
DOI: 10.1038/nature06244
PMID: 17943116
12. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al.; MetaHIT Consortium. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65.
DOI: 10.1038/nature08821
PMID: 20203603
13. Qi Y, Aranda JM, Rodriguez V, Raizada MK, Pepine CJ. Impact of antibiotics on arterial blood pressure in a patient with resistant hypertension - A case report. Int J Cardiol. 2015;201:157-8.
DOI: 10.1016/j.ijcard.2015.07.078
PMID: 26301638
14. Gomez-Arango LF, Barrett HL, McIntyre HD, Callaway LK, Morrison M, Dekker Nitert M; SPRING Trial Group. Increased Systolic and Diastolic Blood Pressure Is Associated With Altered Gut Microbiota Composition and Butyrate Production in Early Pregnancy. Hypertension. 2016;68(4):974-81.
DOI: 10.1161/HYPERTENSIONAHA.116.07910
PMID: 27528065
15. Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann RR, Rauchhaus M, et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet. 1999;353(9167):1838-42.
DOI: 10.1016/S0140-6736(98)09286-1
PMID: 10359409
16. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic Endotoxemia Initiates Obesity and Insulin Resistance. Diabetes. 2007;56(7):1761-72.
DOI: 10.2337/db06-1491
PMID: 17456850
17. Karlsson FH, Fåk F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun. 2012;3(1):1245.
DOI: 10.1038/ncomms2266
PMID: 23212374
18.
19. Ma J, Li H. The Role of Gut Microbiota in Atherosclerosis and Hypertension. Front Pharmacol. 2018;9:1082.
DOI: 10.3389/fphar.2018.01082
PMID: 30319417
20. Ott SJ, El Mokhtari NE, Musfeldt M, Hellmig S, Freitag S, Rehman A, et al. Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease. Circulation. 2006;113(7):929-37.
DOI: 10.1161/CIRCULATIONAHA.105.579979
PMID: 16490835
21. Lam V, Su J, Koprowski S, Hsu A, Tweddell JS, Rafiee P, et al. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J. 2012;26(4):1727-35.
DOI: 10.1096/fj.11-197921
PMID: 22247331
22. 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;11(8):e0160840.
DOI: 10.1371/journal.pone.0160840
PMID: 27505423
23. Gan XT, Ettinger G, Huang CX, Burton JP, Haist JV, Rajapurohitam V, et al. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ Heart Fail. 2014;7(3):491-9.
DOI: 10.1161/CIRCHEARTFAILURE.113.000978
PMID: 24625365
24. Kitai T, Kirsop J, Tang WH. Exploring the Microbiome in Heart Failure. Curr Heart Fail Rep. 2016;13(2):103-9.
DOI: 10.1007/s11897-016-0285-9
PMID: 26886380
25. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382(9889):339-52.
DOI: 10.1016/S0140-6736(13)60595-4
PMID: 23727170
26. Shi K, Wang F, Jiang H, Liu H, Wei M, Wang Z, et al. Gut bacterial translocation may aggravate microinflammation in hemodialysis patients. Dig Dis Sci. 2014;59(9):2109-17.
DOI: 10.1007/s10620-014-3202-7
PMID: 24828917
27. Lin CJ, Chen HH, Pan CF, Chuang CK, Wang TJ, Sun FJ, et al. p-Cresylsulfate and indoxyl sulfate level at different stages of chronic kidney disease. J Clin Lab Anal. 2011;25(3):191-7.
DOI: 10.1002/jcla.20456
PMID: 21567467
28. Tang WHW, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, et al. Gut Microbiota-Dependent Trimethylamine N-oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease. Circ REs. 2015;116(3):448-55.
DOI: 10.1161/CIRCRESAHA.116.305360
PMID: 25599331
29. Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, DeSantis TZ, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013;83(2):308-15.
DOI: 10.1038/ki.2012.345
PMID: 22992469
30. Wang F, Jiang H, Shi K, Ren Y, Zhang P, Cheng S. Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients. Nephrology (Carlton). 2012;17(8):733-8.
DOI: 10.1111/j.1440-1797.2012.01647.x
PMID: 22817644
31. Tang WHW, Wang Z, Fan Y, Levison B, Hazen JE, Donahue LM, et al. Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite trimethylamine-N-oxide in Patients With Heart Failure: Refining the Gut Hypothesis. J Am Coll Cardiol. 2014;64(18):1908-14.
DOI: 10.1016/j.jacc.2014.02.617
PMID: 25444145
32. Ahmadmehrabi S, Tang WH. Gut microbiome and its role in cardiovascular diseases. Curr Opin Cardiol. 2017;32(6):761-6.
DOI: 10.1097/HCO.0000000000000445
PMID: 29023288
33. Tang WHW, Wang Z, Shrestha K, Borowski AG, Wu Y, Troughton RW, et al. Intestinal Microbiota-Dependent Phosphatidylcholine Metabolites, Diastolic Dysfunction, and Adverse Clinical Outcomes in Chronic Systolic Heart Failure. J Card Fail. 2015;21(2):91-6.
DOI: 10.1016/j.cardfail.2014.11.006
PMID: 25459686
34. Rhee EP, Clish CB, Ghorbani A, Larson MG, Elmariah S, McCabe E, et al. J Am Soc Nephrol. 2013;24(8):1330-8.
DOI: 10.1681/ASN.2012101006
PMID: 23687356
35. Wree A, Geisler LJ, Tacke F. Mikrobiom & NASH – enge Komplizen in der Progression von Fettlebererkrankungen TT - Microbiome & NASH – partners in crime driving progression of fatty liver disease. Z Gastroenterol. 2019;57(07):871-82.
DOI: 10.1055/a-0755-2595
PMID: 31288283
36. Zeissig S. Microbial regulation of tumor development and responses to tumor therapy. Z Gastroenterol. 2019;57(7):883-8.
PMID: 31288284
37. Stallmach A, Grunert P, Pieper D, Steube A.. Ulcerative Colitis: Does the Modulation of Gut Microbiota Induce Long-Lasting Remission? Z Gastroenterol. 2019;57(07):834-42.
DOI: 10.1055/a-0874-6603
PMID: 30986885
38. Enck P, Mazurak N. Microbiota and irritable bowel syndrome: A critical inventory. Z Gastroenterol. 2019;57(7):859-70.
PMID: 31288282
39. Skok P. Gastrointestinal tract and associated heart and kidney diseases. In: Radenković S, Šmelcerović A, eds. Kardionefrologija = Cardionephrology. International Cardionephrology and Hypertension Congress. 2019; Ribarska Banja. Niš: Punta; 2019.
40. Jia Q, Li H, Zhou H, Zhang X, Zhang A, Xie Y, et al. Microbiota and irritable bowel syndrome: A critical inventory. Cardiovasc Ther. 2019;2019:5164298.
DOI: 10.1155/2019/5164298
PMID: 31819762
41. Salehi-Abargouei A, Maghsoudi Z, Shirani F, Azadbakht L. Effects of Dietary Approaches to Stop Hypertension (DASH)-style diet on fatal or nonfatal cardiovascular diseases—incidence: a systematic review and meta-analysis on observational prospective studies. Nutrition. 2013;29(4):611-8.
DOI: 10.1016/j.nut.2012.12.018
PMID: 23466047
42. Rifai L, Pisano C, Hayden J, Sulo S, Silver MA. Impact of the DASH diet on endothelial function, exercise capacity, and quality of life in patients with heart failure. Proc Bayl Univ Med Cent. 2015;28(2):151-6.
DOI: 10.1080/08998280.2015.11929216
PMID: 25829641
43. Lopez-Garcia E, Rodriguez-Artalejo F, Li TY, Fung TT, Li S, Willett WC, et al. The Mediterranean-style dietary pattern and mortality among men and women with cardiovascular disease. Am J Clin Nutr. 2014;99(1):172-80.
DOI: 10.3945/ajcn.113.068106
PMID: 24172306
44. De Filippis F, Pellegrini N, Vannini L, Jeffery IB, La Storia A, Laghi L, et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. 2016;65(11):1812-21.
DOI: 10.1136/gutjnl-2015-309957
PMID: 26416813
45. Marques FZ, Nelson E, Chu PY, Horlock D, Fiedler A, Ziemann M, et al. High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation. 2017;135(10):964-77.
DOI: 10.1161/CIRCULATIONAHA.116.024545
PMID: 27927713
46. Lin PP, Hsieh YM, Kuo WW, Lin YM, Yeh YL, Lin CC, et al. Probiotic-fermented purple sweet potato yogurt activates compensatory IGF‑IR/PI3K/Akt survival pathways and attenuates cardiac apoptosis in the hearts of spontaneously hypertensive rats. Int J Mol Med. 2013;32(6):1319-28.
DOI: 10.3892/ijmm.2013.1524
PMID: 24127171
47. Tiihonen K, Tynkkynen S, Ouwehand A, Ahlroos T, Rautonen N. The effect of ageing with and without non-steroidal anti-inflammatory drugs on gastrointestinal microbiology and immunology. Br J Nutr. 2008;100(1):130-7.
DOI: 10.1017/S000711450888871X
PMID: 18279548
48. Zhou X, Li J, Guo J, Geng B, Ji W, Zhao Q, et al. Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction. Microbiome. 2018;6(1):66.
DOI: 10.1186/s40168-018-0441-4
PMID: 29615110
49. Ponziani FR, Zocco MA, D’Aversa F, Pompili M, Gasbarrini A. Eubiotic properties of rifaximin: disruption of the traditional concepts in gut microbiota modulation. World J Gastroenterol. 2017;23(25):4491-9.
DOI: 10.3748/wjg.v23.i25.4491
PMID: 28740337
50. Conraads VM, Jorens PG, De Clerck LS, Van Saene HK, Ieven MM, Bosmans JM, et al. Selective intestinal decontamination in advanced chronic heart failure: a pilot trial. Eur J Heart Fail. 2004;6(4):483-91.
DOI: 10.1016/j.ejheart.2003.12.004
PMID: 15182775
51. Roberts AB, Gu X, Buffa JA, Hurd AG, Wang Z, Zhu W, et al. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nat Med. 2018;24(9):1407-17.
DOI: 10.1038/s41591-018-0128-1
PMID: 30082863
52. Singh R, Chandrashekharappa S, Bodduluri SR, Baby BV, Hegde B, Kotla NG, et al. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat Commun. 2019;10(1):89.
DOI: 10.1038/s41467-018-07859-7
PMID: 30626868
53. Durack J, Lynch S V. The Gut Microbiome: Relationships With Disease and Opportunities for Therapy. J Exp Med. 2019;216(1):20-40.
DOI: 10.1084/jem.20180448
PMID: 30322864
Downloads
Published
Issue
Section
License
The Author transfers to the Publisher (Slovenian Medical Association) all economic copyrights following form Article 22 of the Slovene Copyright and Related Rights Act (ZASP), including the right of reproduction, the right of distribution, the rental right, the right of public performance, the right of public transmission, the right of public communication by means of phonograms and videograms, the right of public presentation, the right of broadcasting, the right of rebroadcasting, the right of secondary broadcasting, the right of communication to the public, the right of transformation, the right of audiovisual adaptation and all other rights of the author according to ZASP.
The aforementioned rights are transferred non-exclusively, for an unlimited number of editions, for the term of the statutory
The Author can make use of his work himself or transfer subjective rights to others only after 3 months from date of first publishing in the journal Zdravniški vestnik/Slovenian Medical Journal.
The Publisher (Slovenian Medical Association) has the right to transfer the rights of acquired parties without explicit consent of the Author.
The Author consents that the Article be published under the Creative Commons BY-NC 4.0 (attribution-non-commercial) or comparable licence.