Gut Bacterial Microbiome and Hypertension: A Narrative Review of Mechanisms, Clinical Implications, and Therapeutic Perspectives
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Abstract
The gut bacterial microbiome (GBM) plays an emerging role in the pathophysiology of chronic diseases, including hypertension (HTN). Growing evidence suggests that gut dysbiosis, defined by an altered microbial composition and diversity, is involved in the onset and progression of HTN. Exploring the underlying mechanisms linking the GBM and HTN paves the way for novel targeted therapeutic strategies. This narrative review aims to synthesize current data on the interactions between the GBM and HTN, highlight the bidirectional nature of this relationship, and discuss the clinical implications of microbiome modulation in hypertension management. Gut dysbiosis leads to increased intestinal permeability, facilitating systemic translocation of lipopolysaccharides, which in turn activate inflammatory (TLR4, NF-κB) and sympathetic pathways, contributing to endothelial dysfunction and elevated blood pressure. Moreover, certain microbial metabolites, such as short-chain fatty acids (SCFAs), exhibit antihypertensive effects, whereas trimethylamine-N-oxide (TMAO) is associated with increased vascular stiffness and activation of the renin–angiotensin–aldosterone system. The relationship between the GBM and HTN is reciprocal: while dysbiosis can promote HTN, HTN itself may disrupt the gut microbial ecosystem. This bidirectional interaction suggests the existence of a pathological vicious cycle. Innovative strategies to modulate the GBM, including the use of probiotics, prebiotics, postbiotics, and specific dietary interventions such as the Dietary Approaches to Stop Hypertension diet, are currently under investigation. The emergence of pharmacological approaches targeting pathogenic microbial metabolites, such as TMAO, also represents a promising avenue toward precision medicine in hypertension.
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References
- Pearce DA, Newsham KK, Thorne MAS, et al. Metagenomic Analysis of a Southern Maritime Antarctic Soil. Frontiers in Microbiology. 2012, 3. https://doi.org/10.3389/fmicb.2012.00403
- Mohajeri MH, Brummer RJM, Rastall RA, et al. The role of the microbiome for human health: from basic science to clinical applications. European Journal of Nutrition. 2018, 57(S1): 1-14. https://doi.org/10.1007/s00394-018-1703-4
- Turnbaugh PJ, Ley RE, Hamady M, et al. The Human Microbiome Project. Nature. 2007, 449(7164): 804-810. https://doi.org/10.1038/nature06244
- Qin J, Li R, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010, 464(7285): 59-65. https://doi.org/10.1038/nature08821
- World Health Organization. Hypertension. 2023. https://www.who.int/news-room/fact-sheets/detail/hypertension
- Clinical Implications. Hypertension. 2015, 65(2): 251-251. https://doi.org/10.1161/hypertensionaha.114.05033
- Lepage P. Le microbiote intestinal humain: Interactions avec l'hôte et dysfonctions. Feuillets de Biologie. 2015, 323: 41–48. https://www.laboratoires-maymat.fr
- Nibali L, Henderson B, eds. The Human Microbiota and Chronic Disease. Published online August 8, 2016. https://doi.org/10.1002/9781118982907
- Wang L, Wang S, Zhang Q, et al. The role of the gut microbiota in health and cardiovascular diseases. Molecular Biomedicine. 2022, 3(1). https://doi.org/10.1186/s43556-022-00091-2
- Buonafine M, Bonnard B, Jaisser F. Mineralocorticoid Receptor and Cardiovascular Disease. American Journal of Hypertension. 2018, 31(11): 1165-1174. https://doi.org/10.1093/ajh/hpy120
- Pluznick JL, Protzko RJ, Gevorgyan H, et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proceedings of the National Academy of Sciences. 2013, 110(11): 4410-4415. https://doi.org/10.1073/pnas.1215927110
- Makaryus JN, Halperin JL, Lau JF. Oral anticoagulants in the management of venous thromboembolism. Nature Reviews Cardiology. 2013, 10(7): 397-409. https://doi.org/10.1038/nrcardio.2013.73
- Pruijm M, Lu Y, Megdiche F, et al. Serum calcification propensity is associated with renal tissue oxygenation and resistive index in patients with arterial hypertension or chronic kidney disease. Journal of Hypertension. 2017, 35(10): 2044-2052. https://doi.org/10.1097/hjh.0000000000001406
- Ley RE, Hamady M, Lozupone C, et al. Evolution of Mammals and Their Gut Microbes. Science. 2008, 320(5883): 1647-1651. https://doi.org/10.1126/science.1155725
- Laja García A, Moráis-Moreno C, Samaniego-Vaesken M, et al. Association between Hydration Status and Body Composition in Healthy Adolescents from Spain. Nutrients. 2019, 11(11): 2692. https://doi.org/10.3390/nu11112692
- Stojanov S, Berlec A, Štrukelj B. The Influence of Probiotics on the Firmicutes/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms. 2020, 8(11): 1715. https://doi.org/10.3390/microorganisms8111715
- Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience of the human gut microbiota. Nature. 2012, 489(7415): 220-230. https://doi.org/10.1038/nature11550
- Thursby E, Juge N. Introduction to the human gut microbiota. Biochemical Journal. 2017, 474(11): 1823-1836. https://doi.org/10.1042/bcj20160510
- Barzilai N, Crandall JP, Kritchevsky SB, et al. Metformin as a Tool to Target Aging. Cell Metabolism. 2016, 23(6): 1060-1065. https://doi.org/10.1016/j.cmet.2016.05.011
- Pluznick JL. Gut microbiota in renal physiology: focus on short-chain fatty acids and their receptors. Kidney International. 2016, 90(6): 1191-1198. https://doi.org/10.1016/j.kint.2016.06.033
- Correction. Journal of the American College of Cardiology. 2013, 62(11): 1039. https://doi.org/10.1016/j.jacc.2013.07.008
- Ma J, Li H. The Role of Gut Microbiota in Atherosclerosis and Hypertension. Frontiers in Pharmacology. 2018, 9. https://doi.org/10.3389/fphar.2018.01082
- Koç F, Mills S, Strain C, et al. The public health rationale for increasing dietary fibre: Health benefits with a focus on gut microbiota. Nutrition Bulletin. 2020, 45(3): 294-308. https://doi.org/10.1111/nbu.12448
- Luchi WM, Crajoinas RO, Martins FL, et al. High blood pressure induced by vitamin D deficiency is associated with renal overexpression and hyperphosphorylation of Na+-K+-2Cl- cotransporter type 2. Journal of Hypertension. 2020, 39(5): 880-891. https://doi.org/10.1097/hjh.0000000000002745
- Kataoka K. The intestinal microbiota and its role in human health and disease. The Journal of Medical Investigation. 2016, 63(1.2): 27-37. https://doi.org/10.2152/jmi.63.27
- Patrick DM, Van Beusecum JP, Kirabo A. The role of inflammation in hypertension: novel concepts. Current Opinion in Physiology. 2021, 19: 92-98. https://doi.org/10.1016/j.cophys.2020.09.016
- Tanet L, Tamburini C, Baumas C, et al. Bacterial Bioluminescence: Light Emission in Photobacterium phosphoreum Is Not Under Quorum-Sensing Control. Frontiers in Microbiology. 2019, 10. https://doi.org/10.3389/fmicb.2019.00365
- Anderegg MD, Gums TH, Uribe L, et al. Physician–Pharmacist Collaborative Management. Hypertension. 2016, 68(5): 1314-1320. https://doi.org/10.1161/hypertensionaha.116.08043
- Willing BP, Russell SL, Finlay BB. Shifting the balance: antibiotic effects on host–microbiota mutualism. Nature Reviews Microbiology. 2011, 9(4): 233-243. https://doi.org/10.1038/nrmicro2536
- Geach T. Defects in BCAA oxidation impair lipid metabolism. Nature Reviews Endocrinology. 2016, 12(10): 560-560. https://doi.org/10.1038/nrendo.2016.149
- Wei G, Liao C, Jian C, et al. Evaluation of miR-34b/c polymorphisms to the risk of ischemic stroke. Journal of Hypertension. 2020, 38(8): 1481-1487. https://doi.org/10.1097/hjh.0000000000002413
- Lin L, Xu S, Cai M, et al. Effects of fecal microbiota transfer on blood pressure in animal models: A systematic review and meta-analysis. Lee LA, ed. PLOS ONE. 2024, 19(4): e0300869. https://doi.org/10.1371/journal.pone.0300869
- Pani L, Pecorelli S, Rosano G, et al. Steps forward in regulatory pathways for acute and chronic heart failure. European Journal of Heart Failure. 2015, 17(1): 3-8. https://doi.org/10.1002/ejhf.209
- Lima Correa B, El Harane N, Gomez I, et al. Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts. Cardiovascular Research. 2020, 117(1): 292-307. https://doi.org/10.1093/cvr/cvaa028
- Tambong JT. Taxogenomics and Systematics of the Genus Pantoea. Frontiers in Microbiology. 2019, 10: 1-13. https://doi.org/10.3389/fmicb.2019.02463
- Krishna U, Paritosh T, Hariom P, et al. The Impact of Gut Microbiota in the Development and Management of Diabetes. Journal of Diabetology. 2025, 16(3): 193-203. https://doi.org/10.4103/jod.jod_143_24
- Cinar AB, Murtomaa H. A holistic food labelling strategy for preventing obesity and dental caries. Obesity Reviews. 2009, 10(3): 357-361. https://doi.org/10.1111/j.1467-789x.2008.00553.x
- Wang PX, Deng XR, Zhang CH, et al. Gut microbiota and metabolic syndrome. Chinese Medical Journal. 2020, 133(7): 808-816. https://doi.org/10.1097/cm9.0000000000000696
- Menni C, Jackson MA, Pallister T, et al. Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain. International Journal of Obesity. 2017, 41(7): 1099-1105. https://doi.org/10.1038/ijo.2017.66
- Bliznyuk A, Hollmann M, Grossman Y. High Pressure Stress Response: Involvement of NMDA Receptor Subtypes and Molecular Markers. Frontiers in Physiology. 2019, 10. https://doi.org/10.3389/fphys.2019.01234
- A. Castro LH, S. de Araújo FH, M. Olimpio MY, et al. Comparative Meta-Analysis of the Effect of Concentrated, Hydrolyzed, and Isolated Whey Protein Supplementation on Body Composition of Physical Activity Practitioners. Nutrients. 2019, 11(9): 2047. https://doi.org/10.3390/nu11092047
- Mezhov V, Ciccutini FM, Hanna FS, et al. Does obesity affect knee cartilage? A systematic review of magnetic resonance imaging data. Obesity Reviews. 2013, 15(2): 143-157. https://doi.org/10.1111/obr.12110
- Franchi F, Rollini F, Angiolillo DJ. Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nature Reviews Cardiology. 2017, 14(6): 361-379. https://doi.org/10.1038/nrcardio.2017.18
- Sanders ME, Merenstein DJ, Reid G, et al. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nature Reviews Gastroenterology & Hepatology. 2019, 16(10): 605-616. https://doi.org/10.1038/s41575-019-0173-3
- Adorni MP, Zimetti F, Lupo MG, et al. Naturally Occurring PCSK9 Inhibitors. Nutrients. 2020, 12(5): 1440. https://doi.org/10.3390/nu12051440
- Capers PL, Fobian AD, Kaiser KA, et al. A systematic review and meta‐analysis of randomized controlled trials of the impact of sleep duration on adiposity and components of energy balance. Obesity Reviews. 2015, 16(9): 771-782. https://doi.org/10.1111/obr.12296
- Patel R, Moffatt JD, Mourmoura E, et al. Effect of reproductive ageing on pregnant mouse uterus and cervix. The Journal of Physiology. 2017, 595(6): 2065-2084. https://doi.org/10.1113/jp273350
- Chhipa H, Kaushik N. Fungal and Bacterial Diversity Isolated from Aquilaria malaccensis Tree and Soil, Induces Agarospirol Formation within 3 Months after Artificial Infection. Frontiers in Microbiology. 2017, 8. https://doi.org/10.3389/fmicb.2017.01286
- Li J, Yousefi K, Ding W, et al. Osteopontin RNA aptamer can prevent and reverse pressure overload-induced heart failure. Cardiovascular Research. 2017, 113(6): 633-643. https://doi.org/10.1093/cvr/cvx016
- Bennett BJ, Vallim TQ de A, Wang Z, et al. Trimethylamine-N-Oxide, a Metabolite Associated with Atherosclerosis, Exhibits Complex Genetic and Dietary Regulation. Cell Metabolism. 2013, 17(1): 49-60. https://doi.org/10.1016/j.cmet.2012.12.011
- Regional patient variability and outcomes in TOPCAT. Nature Reviews Cardiology. 2014, 12(1): 5-5. https://doi.org/10.1038/nrcardio.2014.197
- Schott EM, Farnsworth CW, Grier A, et al. Targeting the gut microbiome to treat the osteoarthritis of obesity. JCI Insight. 2018, 3(8). https://doi.org/10.1172/jci.insight.95997
- Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Medicine. 2013, 19(5): 576-585. https://doi.org/10.1038/nm.3145
- Gao Z, Bumgardner C, Song N, et al. Cotton-textile-enabled flexible self-sustaining power packs via roll-to-roll fabrication. Nature Communications. 2016, 7(1). https://doi.org/10.1038/ncomms11586
- Kim O, Kim H, Choi UH, et al. One-volt-driven superfast polymer actuators based on single-ion conductors. Nature Communications. 2016, 7(1). https://doi.org/10.1038/ncomms13576
- Latif F, Mubbashir A, Khan MS, et al. Trimethylamine N-oxide in cardiovascular disease: Pathophysiology and the potential role of statins. Life Sciences. 2025, 361: 123304. https://doi.org/10.1016/j.lfs.2024.123304