Role of intestinal microbiota changes in cardiovascular diseases pathogenesis
DOI:
https://doi.org/10.14739/2310-1210.2019.5.179462Keywords:
intestinal microbiota, cardiovascular diseases, endotoxin, short-chain fatty acids, trimethylamine, trimethylamine-N-oxideAbstract
Purpose of this article is to clarify the role of intestinal microbiota changes in cardiovascular diseases pathogenesis. In the analysis of intestinal microbiota changes in patients with cardiac pathology, a diversity and lack of research on this issue are notable. Intestinal microflora performs immune, metabolic, synthetic, enzymatic, antitoxic and other functions, providing intestinal colonization resistance. The intestinal microbiota effects on the human body are primarily due to toxic metabolites which can be provisionally divided into five groups: trimethylamine and its derivatives, short-chain fatty acids, endotoxin and bacterial wall products, bile acids and uremic toxins. It is interesting to further study their role in the pathogenesis of heart diseases. For example, bacterial role in trimethylamine, choline metabolism and their effects on the pathogenesis of atherosclerosis. The possibilities of their use as diagnostic markers are studied. However, studies of trimethylamines are usually associated with difficulties, due to their strong dependence on the patient's diet. Trimethylamines are the most studied group of intestinal metabolites, although there are still no reliable ways to correct them. Analysis of short-chain fatty acids requires the identification of each fatty acid individual role, and comparing their content in peripheral blood and stool. Endotoxin is a marker of microbial activity in the intestine. It is an important component of the bacterial cell wall. A study of bile acids metabolism changes influenced by intestinal microbiota also can help to understand disorders of lipid metabolism. An increase in the intestinal microflora uremic toxins (p-cresol, indoxyl sulfate) synthesis is associated with chronic kidney disease. It is promising to develop further ways for correction of the intestinal microbiota composition, which requires a better understanding of cardio-vascular pathology pathogenetic mechanisms.
Conclusions. The study of intestinal microbiota composition is appropriate taking into account synthetic activity of various bacteria. Reviewing the effect of microbial metabolites on the human body and studying the mechanisms of their synthesis, it is possible to understand their role as diagnostic markers and suggest ways of correction.
References
Akopyan, A. N. (2014) Diagnostika i lechenie funkcional'nyлh narushenij motoriki organov pishhevareniнa u detej (Avtoref. dis… dokt. med. nauk) [Diagnosis and treatment of functional disorders of motility of the digestive system in children Dr. med. sci. diss.] [in Russian].
Gyulazyan, N. M., Belaya, O. F., Malov, V. A., Pak, S. G., & Volchkova, E. V. (2014) Lipopolisakharidy/e'ndotoksiny gramotricatel'nykh bakterij: rol' v razvitii intoksikacii [Lipopolysaccharides / endotoxins of gram-negative bacteria: their role in developing intoxicati]. E'pidemiologiya i infekcionnye bolezni, 2, 11–16. [in Russian].
Ivashkin, V. T., & Ivashkin, K. V. (2017) Mikrobiom cheloveka v prilozhenii k klinicheskoj praktike [Human microbiome, applied to clinical practice]. Rossijskij zhurnal gastroe'nterologii gepatologii, koloproktologii, 27(6), 4–13. [in Russian].
Molozhavaya, O. S., Ivahnjuk, T. V., Makarenko, A. N., & Broz, R. V. (2016) Funkcii kishechnoj mikroflory organizma v norme i pri patologii [Physiological functions of intestinal microflora in normal and pathological variants]. Aktualni problemy suchasnoi medytsyny. Visnyk ukrainskoi medychnoi stomatolohichnoi akademii, 16, 4(56), part 1, 333–340. [in Russian].
Rojtberg, G. E., & Strutynskij, A. V. (2014) Vnutrennie bolezni. Sistema organov pishhevareniya. [Internal Diseases. The system of digestive organs]. Moscow: MEDpress-inform. [in Russian].
Chaplin, A. V., Rebrikov, D. V., & Boldyreva, M. N. (2017) Mikrobiom cheloveka [The human microbiome]. Vestnik Rossijskogo gosudarstvennogo medicinskogo universiteta, 2, 5–13. [in Russian].
Yankovskij, D. S., & Dyment, G. S. (2008) Mikroflora i zdorov'e cheloveka [Microflora and human health]. Kyiv: Chervona Ruta-Tours. [in Russian].
Belkaid, Y., & Harrison, O. J. (2017) Homeostatic immunity and the microbiota. Immunity, 46(4), 562–576. doi: 10.1016/j.immuni.2017.04.008 [in Russian].
Chu, H., Duan, Y., Yang, L., & Schnabl, B. (2018). Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease. Gut, 68(2), 359–370. doi: 10.1136/gutjnl-2018-316307
Felisbino, M. B., & McKinsey, T. A. (2018) Epigenetics in Cardiac Fibrosis Emphasis on Inflammation and Fibroblast Activation. JACC Basic Transl Sci, 3(5), 704–715. doi: 10.1016/j.jacbts.2018.05.003
Hsiao, E. Y., McBride, S. W., Hsien, S., Sharon,G., Hyde, E. R., McCue, T., et al. (2013) The microbiota modulates gut physiology and behavioral abnormalities associated with autism. Cell, 155(7), 1451–1463. doi: 10.1016/j.cell.2013.11.024
Han, H., Zhu, J., Zhu, Z., Ni, J., Du, R., Dai, Y., et al. (2015) P-Cresyl Sulfate Aggravates Cardiac Dysfunction Associated With Chronic Kidney Disease by Enhancing Apoptosis of Cardiomyocytes. J Am Heart Assoc, 4(6), e001852. doi: 10.1161/JAHA.115.001852
Han, H., Chen, Y., Zhu, J., Ni, J., Sun, J., & Zhang, R. (2016) Atorvastatin attenuates p-cresyl sulfate-induced atherogenesis and plaque instability in ApoE knockout mice. Mol Med Rep, 14(4), 3122–3128. doi: 10.3892/mmr.2016.5626
Kaji, I., Iwanaga, T., Watanabe, M., Guth, P. H., Engel, E., Kaunitz, J. D., & Akiba, Y. (2015) SCFA transport in rat duodenum. Am J Physiol Gastrointest Liver Physiol, 308(3), G188–G197. doi: 10.1152/ajpgi.00298.2014
Wang, K., Yu, X., Li, Y., Guo, Y., Ge, L., Pu, F., et al. (2018) Bifidobacterium bifidum TMC3115 Can Characteristically Influence Glucose and Lipid Profile and Intestinal Microbiota in the Middle-Aged and Elderly. Probiotics Antimicrob Proteins. doi: 10.1007/s12602-018-9441-8
Kim, H., Kim, D. H., Seo, K. H., Chon, J. W., Nah, S. Y., Bartley, G. E., et al. (2015) Modulation of the intestinal microbiota is associated with lower plasma cholesterol and weight gain in hamsters fed chardonnay grape seed flour. J Agric Food Chem, 63(5), 1460–7. doi: 10.1021/jf5026373
Kindt, A., Liebisch, G., Clavel, T., Haller, D., Hörmannsperger, G., Yoon, H., et al. (2018) The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice. Nat Commun, 9(1), 3760. doi: 10.1038/s41467-018-05767-4
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., et al. (2013) Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med, 19(5), 576–85. doi: 10.1038/nm.3145
Landfald, B., Valeur, J., Berstad, A., & Raa, J. (2017). Microbial trimethylamine-N-oxide as a disease marker: something fishy? Microbial Ecology in Health and Disease, 28(1), 1327309. doi: 10.1080/16512235.2017.1327309
LeBlanc, J. G., Chain, F., Martín, R., Bermúdez-Humarán, L. G., Courau, S., & Langella, P. (2017) Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb Cell Fact, 16(1), 79. doi: 10.1186/s12934-017-0691-z
Li, Y., Liu, X., Du, A., Zhu, X., & Yu, B. (2018) miR-203 accelerates apoptosis and inflammation induced by LPS via targeting NFIL3 in cardiomyocytes. J Cell Biochem., 120(4), 6605–6613. doi: 10.1002/jcb.27955
Mafra, D., Lobo, J. C., Barros, A. F., Koppe, L., Vaziri, N. D., & Fouque, D. (2014) Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease. Future Microbiol, 9(3), 399–410. doi: 10.2217/fmb.13.165
McNabney, S. M., & Henagan, T. M. (2017) Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance. Nutrients, 9(12) E1348. doi: 10.3390/nu9121348
Meijers, B. K., Claes, K., Bammens, B., de Loor, H., Viaene, L., Verbeke, K., et al. (2010) p-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clin. J. Am. Soc. Nephrol, 5(7), 1182–1189. doi: 10.2215/CJN.07971109
Sun, M., Wu, W., Chen, L., Yang, W., Huang, X., Ma, C., et al. (2018) Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nat Commun, 9(1), 3555. doi: 10.1038/s41467-018-05901-2
Nagatomo, Y. and Wilson Tang, W.H. (2015) Intersections between Microbiome and Heart Failure: Revisiting the Gut Hypothesis. J Card Fail, 21(12), 973–980. doi: 10.1016/j.cardfail.2015.09.017
Obeid, R., Awwad, H. M., Keller, M., & Geise, J. (2017) Trimethylamine-N-oxide and its biological variations in vegetarians. Eur J Nutr, 56(8), 2599–2609. doi: 10.1007/s00394-016-1295-9
Orman, M., Bodea, S., Funk, M. A., Campo, A. M., Bollenbach, M., Drennan, C., & Balskus, E.P. (2019) Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria. J Am Chem Soc, 141(1), 33–37. doi: 10.1021/jacs.8b04883
Paramsothy, S., Kamm, M. A., Kaakoush, N. O., Walsh, A. J., van den Bogaerde, J., Samuel, D., et al. (2017) Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet, 389(10075), 1218–1228. doi: 10.1016/S0140-6736(17)30182-4
Pastori, D., Carnevale, R., Nocella, C., Novo, M., Santulli, M., Cammisotto, V., et al. (2017) Gut-Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet. J Am Heart Assoc, 6(6), e005784. doi: 10.1161/JAHA.117.005784
Qi, J., You, T., Li, J., Pan, T., Xiang, L., Han, Y., & Zhu, L. (2018). Circulating trimethylamine N-oxide and the risk of cardiovascular diseases: a systematic review and meta-analysis of 11 prospective cohort studies. Journal of Cellular and Molecular Medicine. 22(1), 185–194. doi: 10.1111/jcmm.13307
Rooks, M. G., & Garrett, W. S. (2016) Gut microbiota, metabolites and host immunity. Nat Rev Immunol, 16(6), 341–352. doi: 10.1038/nri.2016.42
Rowland, I., Gibson, G., Heinken, A., Scott, K., Swann, J., Thiele, I., & Tuohy, K. (2018) Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr, 57(1), 1–24. doi: 10.1007/s00394-017-1445-8
Singh, V., Chassaing, B., Zhang, L., San Yeoh, B., Xiao, X., Kumar, M., et al. (2015) Microbiota-Dependent Hepatic Lipogenesis Mediated by Stearoyl CoA Desaturase 1 (SCD1) Promotes Metabolic Syndrome in TLR5-Deficient Mice. Cell Metab, 22(6), 983–96. doi: 10.1016/j.cmet.2015.09.028
Skye, S. M., Zhu, W., Romano, K. A., Guo, C. J., Wang, Z., Jia, X., et al. (2018) Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential. Circ Res, 123(10), 1164–1176. doi: 10.1161/CIRCRESAHA.118.313142
Tang, W. H., Kitai, T., & Hazen, S. L. (2017) Gut Microbiota in Cardiovascular Health and Disease. Circ Res, 120(7), 1183–1196. doi: 10.1161/CIRCRESAHA.117.309715
Verdi, S., Jackson, M. A., Beaumont, M., Bowyer R. C. E., Bell, J. T., Spector, T. D. & Steves, C. J. (2018) Steves An Investigation Into Physical Frailty as a Link Between the Gut Microbiome and Cognitive Health. Front Aging Neurosci, 10, 398. doi: 10.3389/fnagi.2018.00398
Wang, C. H., Cheng, M. L., Liu, M. H., Shiao, M. S., Hsu, K. H., Huang, Y. Y., et al. (2016) Increased p-cresyl sulfate level is independently associated with poor outcomes in patients with heart failure. Heart Vessels, 31(7), 1100–8. doi: 10.1007/s00380-015-0702-0
Wang, S., Huang, M., You, X., Zhao, J., Chen, L., Wang, L., et al. (2018) Gut microbiota mediates the anti-obesity effect of calorie restriction in mice. Sci Rep, 8, 13037. doi: 10.1038/s41598-018-31353-1
Wang, Y., Yin, J., Wang, C., Hu, H., Li, X., Xue, M., et al. (2019) Microglial Mincle receptor in the PVN contributes to sympathetic hyperactivity in acute myocardial infarction rat. J Cell Mol Med, 23(1), 112–125. doi: 10.1111/jcmm.13890
Zhu, W., Wang, Z., Tang, W. H. W., & Hazen, S. L. (2017) Gut Microbe-Generated TMAO from Dietary Choline Is Prothrombotic in Subjects. Circulation., 135(17), 1671–1673. doi: 10.1161/CIRCULATIONAHA.116.025338
Zhu, W., Gregory, J. C., Org, E., Buffa, J. A., Gupta, N., Wang, Z., et al. (2016) Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell, 165(1), 111–124. doi: 10.1016/j.cell.2016.02.011
Li, X. S., Wang, Z., Cajka, T., Buffa, J. A., Nemet, I., Hurd, A. G., et al. (2018) Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk. JCI Insight, 3(6), e99096. doi: 10.1172/jci.insight.99096
Yamagami, F., Tajiri, K., Doki, K., Hattori, M., Honda, J., Aita, S., et al. (2018) Indoxyl Sulphate is Associated with Atrial Fibrillation Recurrence after Catheter Ablation. Sci Rep, 8(1), 17276. doi: 10.1038/s41598-018-35226-5
Ye, Y., Jia, X., Bajaj, M., & Birnbaum, Y. (2018) Dapagliflozin Attenuates Na+/H+ Exchanger-1 in Cardiofibroblasts via AMPK Activation. Cardiovasc Drugs Ther, 32(6), 553–558. doi: 10.1007/s10557-018-6837-3
Yu, L., Meng, G., Huang, B., Zhou, X., Stavrakis, S., Wang, M., et al. (2018) A potential relationship between gut microbes and atrial fibrillation: Trimethylamine N-oxide, a gut microbe-derived metabolite, facilitates the progression of atrial fibrillation. Int J Cardiol, 255, 92–98. doi: 10.1016/j.ijcard.2017.11.071
Zhu, Q., Gao, R., Zhang, Y., Pan, D., Zhu, Y., Zhang, X., et al. (2018) Dysbiosis signatures of gut microbiota in coronary artery disease. Physiol Genomics, 50(10), 893–903. doi: 10.1152/physiolgenomics.00070.2018
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
