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Abstract
Background: Hypertension is a persistently elevated arterial blood pressure called the silent killer because sufferers often do not show signs and symptoms. Low Short Chain Fatty Acids (SCFA) is a risk factor for hypertension. Therefore, many efforts have been made in overcoming hypertension through the role of SCFA.
Objective: This review article was conducted to see the SCFA mechanism against the incidence of hypertension so that it is hoped that we can find medicinal plants that can prevent and treat hypertension.
Method: This article is compiled based on a review of several works of literature related to the role of SCFA in hypertension from articles published in the electronic database.
Results: The SCFA mechanism is involved in lowering blood pressure through G-protein coupled receptors (GPCRs). Acetate binding to GPR43 causes hyperpolarization of the colonic epithelium, propionate activates GPR41 signals located in the vascular endothelium and butyrate binds to GPR109a and exerts anti-inflammatory effects. It was also found that giving baicalin and olive oil was shown to increase SCFA-producing bacteria.
Conclusion: The role of SCFA in the development of hypertension occurs through the mechanism of diffusion and transport of solutes from SCFA which then activates GPCRs including GPR43, GPR41, and GPR109a so that they have a vasodilating effect by reducing inflammation, improving intestinal permeability, decreasing sympathetic nerve activity, and increasing Treg cells.
Keywords: gut microbiota; SCFA; hypertension
Intisari
Latar belakang: Hipertensi adalah tekanan darah arteri yang meningkat secara persisten disebut juga silent killer karena penderita sering tidak menampakkan tanda dan gejala. Rendahnya Short Chain Fatty Acids (SCFA) menjadi faktor risiko dari hipertensi. Oleh karena itu, telah banyak upaya yang dilakukan dalam mengatasi hipertensi melalui peran SCFA.
Tujuan: Review artikel ini dilakukan untuk melihat mekanisme SCFA terhadap kejadian hipertensi sehingga diharapkan dapat mencari tanaman obat yang dapat mencegah dan mengobati hipertensi.
Metode: Artikel ini disusun berdasarkan review beberapa literatur yang terkait peran SCFA dalam hipertensi dari artikel yang diterbitkan di electronic database.
Hasil: Mekanisme SCFA yang terlibat dalam penurunan tekanan darah melalui G-protein coupled receptors (GPCRs). Asetat mengikat GPR43 menyebabkan hiperpolarisasi epitel kolon, propionat mengaktifkan sinyal GPR41 yang terletak di endotel vaskuler dan butirat mengikat GPR109a memberikan efek anti-inflamasi.
Kesimpulan: Peran SCFA dalam perkembangan hipertensi terjadi melalui mekanisme adanya difusi dan transport zat terlarut dari SCFA yang kemudian mengaktivasi GPCR termasuk GPR43, GPR41 dan GPR109a sehingga memberikan efek vasodilatasi dengan menurunkan inflamasi, memperbaiki permeabilitas usus, menurunkan aktivitas saraf simpatis dan meningkatkan sel Treg.
Kata kunci: mikrobiota usus; SCFA; hipertensi
Keywords
Article Details
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References
Bartolomaeus, H., alogh, A., Yakoub, M., Homann, S., Markó, L., Höges, S. (2019). Short-Chain Fatty Acid Propionate Protects. Circulation, 1407–1421. https://doi.org/10.1161/CIRCULATIONAHA.118.036652
Battson, M. L., Lee, D. M., Weir, T. L., & Gentile, C. L. (2018). The gut microbiota as a novel regulator of cardiovascular function and disease. Journal of Nutritional Biochemistry, 56, 1–15. https://doi.org/10.1016/j.jnutbio.2017.12.010
Bier, A., Braun, T., Khasbab, R., Di Segni, A., Grossman, E., Haberman, Y., & Leibowitz, A. (2018). A high salt diet modulates the gut microbiota and short chain fatty acids production in a salt-sensitive hypertension rat model. Nutrients, 10(9), 1–10. https://doi.org/10.3390/nu10091154
Calderón-pérez, L., Gosalbes, M. J., Yuste, S., Valls, R. M., Pedret, A., Llauradó, E., Jimenez-herna, N., Artacho, A., Pla-pagà, L., Companys, J., Ludwig, I., Romero, M., Rubió, L., & Solà, R. (2020). Gut metagenomic and short chain fatty acids signature in hypertension : a cross-sectional study. Scientific Reports, 1–16. https://doi.org/10.1038/s41598-020-63475-w
Callejo, M., Mondejar-Parreño, G., Barreira, B., Izquierdo-Garcia, J. L., Morales-Cano, D., Esquivel-Ruiz, S., Moreno, L., Cogolludo, Á., Duarte, J., & Perez-Vizcaino, F. (2018). Pulmonary Arterial Hypertension Affects the Rat Gut Microbiome. Scientific Reports, 8(1), 1–10. https://doi.org/10.1038/s41598-018-27682-w
Chen, J., He, X., & Huang, J. (2014). Diet Effects in Gut Microbiome and Obesity. Journal of Food Science, 79(4). https://doi.org/10.1111/1750-3841.12397
Cresci, G. A., Thangaraju, M., Mellinger, J. D., Liu, K., & Ganapathy, V. (2010). Colonic gene expression in conventional and germ-free mice with a focus on the butyrate receptor GPR109A and the butyrate transporter SLC5A8. Journal of Gastrointestinal Surgery, 14(3), 449–461. https://doi.org/10.1007/s11605-009-1045-x
DiPiro, J. T., Yee, G. C., Posey, L. M., Haines, S. T., Nolin, T. D., & Ellingrod, V. (2020). Pharmacotherapy: A Pathophysiologic Approach, Eleventh Edition (Eleventh). McGraw-Hill Education Companies.
Ferrari, R. (2015). Writing narrative style literature reviews. Medical Writing, 24(4), 230–235. https://doi.org/10.1179/2047480615z.000000000329
Hidalgo, M., Prieto, I., Abriouel, H., Villarejo, A. B., Ramírez-Sánchez, M., Cobo, A., Benomar, N., Gálvez, A., & Martínez-Cañamero, M. (2018). Changes in Gut Microbiota Linked to a Reduction in Systolic Blood Pressure in Spontaneously Hypertensive Rats Fed an Extra Virgin Olive Oil-Enriched Diet. Plant Foods for Human Nutrition, 73(1), 6–11. https://doi.org/10.1007/s11130-017-0650-1
Hsu, C. N., Chang-Chien, G. P., Lin, S., Hou, C. Y., & Tain, Y. L. (2019). Targeting on Gut Microbial Metabolite Trimethylamine-N-Oxide and Short-Chain Fatty Acid to Prevent Maternal High-Fructose-Diet-Induced Developmental Programming of Hypertension in Adult Male Offspring. Molecular Nutrition and Food Research, 63(18), 1–10. https://doi.org/10.1002/mnfr.201900073
Juanola, O., Ferrusquía-Acosta, J., García-Villalba, R., Zapater, P., Magaz, M., Marín, A., Olivas, P., Baiges, A., Bellot, P., Turon, F., Hernández-Gea, V., González-Navajas, J. M., Tomás-Barberán, F. A., García-Pagán, J. C., & Francés, R. (2019). Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis. FASEB Journal, 33(10), 11595–11605. https://doi.org/10.1096/fj.201901327R
Kasubuchi, M., Hasegawa, S., Hiramatsu, T., Ichimura, A., & Kimura, I. (2015). Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients, 7(4), 2839–2849. https://doi.org/10.3390/nu7042839
Kaye, D. M., Shihata, W. A., Jama, H. A., Tsyganov, K., Ziemann, M., Kiriazis, H., Horlock, D., Vijay, A., Giam, B., Vinh, A., Johnson, C., Fiedler, A., Donner, D., Snelson, M., Coughlan, M. T., Phillips, S., Du, X. J., El-Osta, A., Drummond, G., … Marques, F. Z. (2020). Deficiency of Prebiotic Fiber and Insufficient Signaling through Gut Metabolite-Sensing Receptors Leads to Cardiovascular Disease. Circulation, 1393–1403. https://doi.org/10.1161/CIRCULATIONAHA.119.043081
Kemenkes RI. (2018). Hasil Utama Riset Kesehatan Dasar (RISKESDAS). Kemenkes RI.
Ma, J., & Li, H. (2018). The role of gut microbiota in atherosclerosis and hypertension. Frontiers in Pharmacology, 9(SEP), 1–14. https://doi.org/10.3389/fphar.2018.01082
Marques, F. Z., Nelson, E., Chu, P. Y., Horlock, D., Fiedler, A., Ziemann, M., Tan, J. K., Kuruppu, S., Rajapakse, N. W., El-Osta, A., Mackay, C. R., & Kaye, D. M. (2017). High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation, 135(10), 964–977. https://doi.org/10.1161/CIRCULATIONAHA.116.024545
Mell, B., Jala, V. R., Mathew, A. V., Byun, J., Waghulde, H., Zhang, Y., Haribabu, B., Vijay-Kumar, M., Pennathur, S., & Joe, B. (2015). Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiological Genomics, 47(6), 187–197. https://doi.org/10.1152/physiolgenomics.00136.2014
Miyamoto, J., Ohue-Kitano, R., Mukouyama, H., Nishida, A., Watanabe, K., Igarashi, M., Irie, J., Tsujimoto, G., Satoh-Asahara, N., Itoh, H., & Kimura, I. (2019). Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions. Proceedings of the National Academy of Sciences of the United States of America, 116(47), 23813–23821. https://doi.org/10.1073/pnas.1912573116
Natarajan, N., Hori, D., Flavahan, S., Steppan, J., Flavahan, N. A., Berkowitz, D. E., & Pluznick, J. L. (2016). Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiological Genomics, 48(11), 826–834. https://doi.org/10.1152/physiolgenomics.00089.2016
Node, J. O. K. (2019). Gut microbiota and hypertension. Hypertension Research, 42, 741–743. https://doi.org/10.1038/s41440-018-0203-5
Onyszkiewicz, M., Gawrys-Kopczynska, M., Konopelski, P., Aleksandrowicz, M., Sawicka, A., Koźniewska, E., Samborowska, E., & Ufnal, M. (2019). Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors. Pflugers Archiv European Journal of Physiology, 471(11–12), 1441–1453. https://doi.org/10.1007/s00424-019-02322-y
Pluznick, J. L., Protzko, R. J., Gevorgyan, H., Peterlin, Z., Sipos, A., Han, J., Brunet, I., Wan, L. X., Rey, F., Wang, T., Firestein, S. J., Yanagisawa, M., Gordon, J. I., Eichmann, A., Peti-Peterdi, J., & Caplan, M. J. (2013). Olfactory receptor responding to gut microbiotaderived signals plays a role in renin secretion and blood pressure regulation. Proceedings of the National Academy of Sciences of the United States of America, 110(11), 4410–4415. https://doi.org/10.1073/pnas.1215927110
Richards, E. M., Pepine, C. J., Raizada, M. K., & Kim, S. (2017). The Gut, Its Microbiome, and Hypertension. Current Hypertension Reports, 19(4), 1–11. https://doi.org/10.1007/s11906-017-0734-1
Roshifanni, S. (2016). Risiko Hipertensi Pada Orang Dengan Pola Tidur Buruk (Studi di Puskesmas Tanah Kalikedinding Surabaya). Jurnal Berkala Epidemiologi, 4(3), 384–395. https://doi.org/10.20473/jbe.v4i3
Scholes, S., Conolly, A., & Mindell, J. S. (2020). Income-based inequalities in hypertension and in undiagnosed hypertension: Analysis of Health Survey for England data. Journal of Hypertension, 38(5), 912–924. https://doi.org/10.1097/HJH.0000000000002350
Toral, M., Robles-Vera, I., De La Visitación, N., Romero, M., Yang, T., Sánchez, M., Gómez-Guzmán, M., Jiménez, R., Raizada, M. K., & Duarte, J. (2019). Critical role of the interaction gut microbiota-sympathetic nervous system in the regulation of blood pressure. Frontiers in Physiology, 10(MAR), 1–14. https://doi.org/10.3389/fphys.2019.00231
Verhaar, B. J. H., Collard, D., Prodan, A., Levels, J. H. M., Zwinderman, A. H., Bäckhed, F., Vogt, L., Peters, M. J. L., Muller, M., Nieuwdorp, M., & van den Born, B. J. H. (2020). Associations between gut microbiota, faecal short-chain fatty acids, and blood pressure across ethnic groups: the HELIUS study. European Heart Journal, 41(44), 4259–4267. https://doi.org/10.1093/eurheartj/ehaa704
Weber, M. A., Schiffrin, E. L., White, W. B., Mann, S., Lindholm, L. H., Kenerson, J. G., Flack, J. M., Carter, B. L., Materson, B. J., Ram, C. V. S., Cohen, D. L., Cadet, J. C., Jean-Charles, R. R., Taler, S., Kountz, D., Townsend, R. R., Chalmers, J., Ramirez, A. J., Bakris, G. L., … Harrap, S. B. (2014). Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension Clinical Practice Guidelines for the Management of Hypertension in the Comm. Journal of Clinical Hypertension, 16(1), 14–26. https://doi.org/10.1111/jch.12237
WHO. (2015). Hypertension 13 (Issue September 2019). https://www.who.int/news-room/fact-sheets/detail/hypertension
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