Figure 2 Mechanisms of the gut–autonomic

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Laurence Macia, PhD 5th European Immunology & Innate Immunity

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Figure 2 Mechanisms of the gut–autonomic nervous system–cardiorenal axis that regulate blood pressure Figure 2 | Mechanisms of the gut–autonomic nervous system–cardiorenal axis that regulate blood pressure. a | A diet rich in resistant starches, which results in increased release of short-chain fatty acids (SCFAs), has several systemic effects that lead to a decrease in blood-pressure levels and cardiovascular disease in general. In the lung, SCFAs downregulate signalling pathways related to cardiac fibrosis, cardiac necrosis and cell death, and cardiovascular system development and function. Fibre and the SCFA acetate function independently of the G-coupled protein receptor (GPCR) GPR43, but act through histone deacetylase (HDAC9) in the lung. In the heart, fibre and acetate upregulate circadian rhythm pathways and downregulate mitogen-activated protein kinase (MAPK), Wnt, and transforming growth factor (TGF)-β signalling. In the kidney, fibre and acetate upregulate pathways related to GPCR ligand binding, circadian rhythm, and intestinal immune network for immunoglobulin (Ig) A production, and downregulate pro-inflammatory IL-1 signalling and the renin–angiotensin–aldosterone system (RAAS). In the kidney, the SCFA propionate seems to act through the olfactory receptor (Olfr78 in mice or OR51E2 in humans) and GPR41 (Table 1). b | Experimental models of hypertension, such as the spontaneously hypertensive rat (SHR) and the angiotensin II mouse model, have higher sympathetic neuronal communication between the gut and the hypothalamic paraventricular nucleus. Both animal models have a leaky intestinal barrier with increased permeability, fibrosis, and inflammatory markers, combined with altered tight junction proteins and decreased blood flow. The SHRs also have increased splanchnic sympathetic nerve activity and higher tyrosine hydroxylase levels in the small intestine. Together, these studies suggest the presence of a gut–sympathetic nervous system–cardiorenal axis in the regulation of blood pressure. Marques, F. Z. et al. (2017) Beyond gut feelings: how the gut microbiota regulates blood pressure Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.120