We read with great interest the timely Review by Dagbasi et al.1, which evaluates the translational potential of targeting short-chain fatty acids (SCFAs) for disease prevention.
Yet, this Review overlooked blood pressure (BP) regulation, the clinical endpoint for which SCFA supplementation has been evaluated most rigorously in humans.
Preclinical findings consistently show, across models and independent groups, that SCFAs attenuate hypertension, cardiorenal fibrosis and hypertrophy2,3,4.
Human genetic analyses further support a causal role for these receptors in BP regulation, with variants associated with reduced receptor expression linked to a higher prevalence of hypertension5.
This receptor-level evidence highlights the complexity of SCFA biology that the Review otherwise discusses carefully.
We read with great interest the timely Review by Dagbasi et al.1, which evaluates the translational potential of targeting short-chain fatty acids (SCFAs) for disease prevention. Yet, this Review overlooked blood pressure (BP) regulation, the clinical endpoint for which SCFA supplementation has been evaluated most rigorously in humans.
Preclinical findings consistently show, across models and independent groups, that SCFAs attenuate hypertension, cardiorenal fibrosis and hypertrophy2,3,4. As highlighted in the Review, the olfactory receptor OR51E2 (also known as Olfr78 in mice) in the juxtaglomerular apparatus modulates renin release1, while other G protein-coupled receptors, FFAR2 and FFAR3 (also known as GPR43 and GPR41, respectively), shape immune pathways implicated in hypertension and end-organ damage4,5. Human genetic analyses further support a causal role for these receptors in BP regulation, with variants associated with reduced receptor expression linked to a higher prevalence of hypertension5. This receptor-level evidence highlights the complexity of SCFA biology that the Review otherwise discusses carefully.
