Gut Microbiota in Hypertension

Pedro A. Jose; Dominic Raj


Curr Opin Nephrol Hypertens. 2015;24(5):403-409. 

In This Article

Gut Microbiota and Gastrorenal Axis

There are monoamine-containing enterochromaffin cells in the mucosa and submucosa of different portions of the stomach and small intestines.[71] The gut microbiota can influence the ability of enterochromaffin cells to produce serotonin, dopamine, and norepinephrine that can influence the behavior of the host, termed brain gut microbiome axis,[72,73] and renal function, termed gastrorenal reflex.[74,75] The absence of gut microbiota has been reported to increase anxiety-like behavior and decreased dopamine turnover in the frontal cortex, hippocampus, and striatum in response to acute stress in rats.[76] Norepinephrine, released in response to stress, can also increase the growth and production of virulence-associated factors of gram-negative bacteria. Gut-germ-free stress-sensitive F344 rats had abnormal behavior associated with increased glucocorticoid mRNA, but decreased dopamine turnover in the hippocampus.[77] However, in BALB/c salt-resistant mice, the oral administration of antibiotics increased exploratory behavior that was not due to changes in gastrointestinal transmitters, such as serotonin, norepinephrine, and dopamine.[78] By contrast, specific pathogen-free mice had increased production of norepinephrine and dopamine in the cecum and colon.[79] Dopamine, via D1-like receptors, can inhibit Na+, K+ ATPase activity, and electrolyte transport in the jejunum of young but not adult rats.[80] In adult rats, D1-like receptors stimulate potassium secretion in the duodenum[81] and inhibit ileal ion transport.[82]

Dietary factors may also influence intestinal L-3,4-dihydroxyphenylalanine (L-DOPA) concentrations, although the effect of gut microbiota in this process is unknown. A 2-week intake of a low-salt diet was associated with increased dopamine, but decreased L-DOPA levels in the jejunal mucosa. By contrast, high salt intake markedly increased the tissue levels of both dopamine and L-DOPA without changes in dopamine/L-DOPA ratios.[83] The major mechanism for the increase in renal dopamine production with salt loading has been suggested to be caused by neural L-DOPA spill-over into the circulation.[84,85] Dopamine, produced in the kidney, and not converted to norepinephrine, is responsible for at least 50% of sodium excretion during conditions of moderate sodium excess.[32–34] However, gastrin secreted by G cells in the stomach and duodenum and released into the circulation[39,86] may aid in this process. Gastrin is taken up by renal cortical tubules to a greater extent than the other enterokinases released after a meal.[87] Gastrin then acts on its receptor – the cholecystokinin B receptor expressed in several nephron segments[88] – to increase renal dopamine production by increasing the renal tubular uptake of L-DOPA (unpublished data). Gastrin synergistically interacts with renal D1 receptors to inhibit sodium transport, enabling the excretion of a sodium load.[74,88–90]