Blood pressure is thought to be partially mediated by the gut microbiome,1-3 and this effect may be due to the relationship between the gut and immune and nervous system modulation, and to poorer metabolic health, which is also associated with high blood pressure.4
Several points suggest a relationship between the gut microbiota and the regulation of blood pressure5:
- High intakes of fruit, vegetables, and fibre are associated with lower blood pressure levels.
- Short-chain fatty acids (such as acetate,6 butyrate,7, 8 and propionate) which are released by the fermentation of fibres in the gut, are also linked to lower blood pressure.
- Limited evidence suggests that the manipulation of the gut microbiota (such as through faecal transplants, or the use of antibiotics or probiotics) might be novel therapeutic approaches for the treatment of hypertension.
- When faecal microbiota from hypertensive rats is transplanted to normotensive rats, they develop high blood pressure.9
Short-chain fatty acids are thought to reduce blood pressure and heart rate by acting on G-protein coupled receptors and vagal signalling,7, 8 an effect observed in mice and not associated with renin, or sodium intake.8 Also, a decrease in blood pressure was associated with lowering of Veillonellaceae, which are succinate‐producing bacteria.10 However, in children with chronic kidney disease, higher levels of the (typically beneficial) short-chain fatty acids propionate and butyrate were instead associated with greater abnormal blood pressure readings in one study.11
Short-chain fatty acids are thought to reduce blood pressure and heart rate
Chronic inflammation and intestinal permeability are also associated with hypertension. Zonulin, a key regulator of intestinal permeability (or ‘leaky gut’) is a predictor of systolic blood pressure.12 Fasting also reduces blood pressure and while this has typically been considered to be related to the metabolic effects of reducing insulin levels, this effect may also result from alterations to the microbiome and short-chain fatty acids.13
In human studies, both hypertension and systolic BP were inversely associated with measures of α-diversity of the microbiome.14 Short-chain fatty acids (esp. butyrate),15, 16 and lower Odoribacter15andbutyrate levels are also associated with higher blood pressure, and in children, greater proportions of Bacteroides, Collinsella, and Coprococcus catus and lower amounts of butyrate-producing Lachnospira species are associated with higher systolic blood pressure. In mothers, higher systolic blood pressure was associated with Lachnoclostridium symbiosum, and lower numbers of butyrate-producing bacteria such as Eubacterium eligens and Porphyromonadaceae Butyricimonas.17
Hypertension is inversely associated with measures of α-diversity of the microbiome
However, there are likely to be gender and ethno-genetic differences. It has been demonstrated that Black and White Americans with hypertension have different gut microbiomes and that these microbiome signatures differ in composition and function and contribute to different metabolites (like different ratios of short-chain fatty acids). There is also more oxidative stress, inflammation, and gut ischemia in black people with hypertension and this might be partially genetic and partially driven by socioeconomic factors.18
References
1. Jama HA, Kaye DM, Marques FZ. The gut microbiota and blood pressure in experimental models. Current Opinion in Nephrology and Hypertension. 2019;28(2).
2. Raizada MK, Joe B, Bryan NS, Chang EB, Dewhirst FE, Borisy GG, et al. Report of the National Heart, Lung, and Blood Institute Working Group on the Role of Microbiota in Blood Pressure Regulation. Hypertension. 2017;70(3):479-85.
3. Al Khodor S, Reichert B, Shatat IF. The Microbiome and Blood Pressure: Can Microbes Regulate Our Blood Pressure? Frontiers in Pediatrics. 2017;5(138).
4. Yang T, Zubcevic J. Gut–Brain Axis in Regulation of Blood Pressure. Frontiers in Physiology. 2017;8(845).
5. Marques FZ, Mackay CR, Kaye DM. Beyond gut feelings: how the gut microbiota regulates blood pressure. Nature Reviews Cardiology. 2018;15(1):20-32.
6. Poll B, Steppan J, Lester L, Berkowitz D, Pluznick J. A short chain fatty acid produced by the gut microbiota plays a role in blood pressure regulation and cardiac contractility. The FASEB Journal. 2019;33(1_supplement):569.19-.19.
7. Ufnal M, Onyszkiewicz M, Gawrys M, Huc T, Aleksandrowicz M, Sawicka A, et al. Butyric Acid, a Gut Bacteria-Produced Metabolite, Decreases Arterial Blood Pressure via a Gut-Vagus Nerve Signaling in Rats. The FASEB Journal. 2019;33(1_supplement):516.8-.8.
8. Natarajan N, Hori D, Flavahan S, Steppan J, Flavahan NA, Berkowitz DE, et al. Gut Microbiota in Health and Disease: Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiological Genomics. 2016;48(11):826.
9. Yang T, Larkin R, Silva CB, Donertas B, Colon-Perez L, Awadallah N, et al. Abstract 084: Gut Dysbiosis Impairs Serotonergic Gut-Brain Axis and Increases Blood Pressure. Hypertension. 2019;74(Suppl_1):A084-A.
10. Chakraborty S, Galla S, Cheng X, Yeo J-Y, Mell B, Chiu N, et al. Reshaping commensal gut microbiota in early life lowers blood pressure potentially via a succinate mediated mechanism. The FASEB Journal. 2020;34(S1):1-.
11. Hsu C-N, Lu P-C, Hou C-Y, Tain Y-L. Blood Pressure Abnormalities Associated with Gut Microbiota-Derived Short Chain Fatty Acids in Children with Congenital Anomalies of the Kidney and Urinary Tract. Journal of Clinical Medicine. 2019;8(8):1090.
12. Kim S, Goel R, Kumar A, Qi Y, Lobaton G, Hosaka K, et al. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure. Clinical Science. 2018;132(6):701-18.
13. Balogh A, Bartolomaeus H, Loeber U, Avery EG, Steckhan N, Marko L, et al. Fasting alters the gut microbiome with sustained blood pressure and body weight reduction in metabolic syndrome patients. medRxiv. 2020:2020.02.23.20027029.
14. Sun S, Lulla A, Sioda M, Winglee K, Wu MC, Jacobs DR, et al. Gut Microbiota Composition and Blood Pressure. Hypertension. 2019;73(5):998-1006.
15. Gomez-Arango LF, Barrett HL, McIntyre HD, Callaway LK, Morrison M, Nitert MD. 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.
16. Huart J, Leenders J, Taminiau B, Descy J, Saint-Remy A, Daube G, et al. Gut Microbiota and Fecal Levels of Short-Chain Fatty Acids Differ Upon 24-Hour Blood Pressure Levels in Men. Hypertension. 2019;74(4):1005-13.
17. Differding M, Hivert M-F, Doyon M, Bouchard L, Perron P, Guérin R, et al. Gut Microbiome Composition Is Associated with Blood Pressure in Mother-Child Pairs 5 Years After Birth. Current Developments in Nutrition. 2020;4(Supplement_2):1555-.
18. Walejko JM, Kim S, Goel R, Handberg EM, Richards EM, Pepine CJ, et al. Gut microbiota and serum metabolite differences in African Americans and White Americans with high blood pressure. International Journal of Cardiology. 2018;271:336-9.
