Hypertension is a widespread condition which may cause cardiovascular events when left untreated. If high blood pressure (BP) is noticed at all, it is mostly only sub-optimally controlled making nutritional interventions a cost-effective and safe preventive measure and an alternative to medical treatment. Previous studies have shown that increased fibre consumption reduces BP which was particularly effective in hypertensive subjects. Fibres are indigestible and hence are available for fermentation by the colonic microbiota which produces the short chain fatty acids (SCFAs) acetate, propionate and butyrate. Intriguingly, recent studies carried out in mice showed that SCFAs can reduce BP. Therefore, we hypothesised that gut microbiota-derived SCFAs can (1) reduce BP in middle-aged male volunteers and (2) influence the protein expression of BP regulatory systems in a cellular model. As the development of a cellular angiotensin II-induced hypertension model was unsuccessful, the effects of SCFAs on a molecular level were assessed in unstimulated human aortic endothelial cells (HAECs). The expression of proteins involved in the BP regulating renin angiotensin system (RAS) was assessed by western blotting. Additionally, a human supplementation trial is being carried out looking at the acute consumption of a low (0.16 g) and high (2.35 g) propionate dose on BP and other cardiovascular markers in middle-aged male volunteers. In vitro work showed that SCFAs did not affect RAS expression in HAECs. However, acute propionate supplementation influenced BP and its regulation. Preliminary data show, that while a high propionate dose led to increases in plasma propionate by on average 4 µM and acetate levels with concurrent increases in BP, arterial stiffness and plasma renin concentration, a low propionate dose resulted in plasma propionate increases of about 0.5 µM with simultaneous reductions in systolic BP. Taken together, these results suggest that SCFAs play a regulatory role in the homoeostasis of BP.