Gastro-renal communication: sniffing and tasting

The Reports referred to in this Introduction are from a session on Gastro Renal communication organised by Pedro Jose at the Experimental Biology 2015 Meeting.

The gastrointestinal tract and the kidney are the major organs involved in the regulation of fluid and electrolyte balance. The concept that these two organs communicate with each other is not new but the pathways by which they communicate are now better understood. The gastrointestinal tract responds to ingested nutrients, ions, and toxins by releasing enterokines and other factors that affect renal function (1–4). These enterokines and factors can affect ion transport in the gastrointestinal tract and the kidney (5). These two organs share many of the pathways involved in ion and fluid transport. Thus, the sodium pump, Na⁺,K⁺-ATPase, is present at the basolateral membrane and sodium hydrogen exchanger type 3 is present at the apical membrane of the epithelial cells lining the gastrointestinal tract and the nephron, thus enabling the regulation of both the excretion and absorption (gastrointestinal tract) and reabsorption of ions (nephron). Indeed, some have suggested that the intestines are more or less like “uncoiled” nephrons. Dr. Soares da Silva discusses the role played by enterochromaffin cells in the production of catecholamines, such as dopamine that can inhibit and serotonin that can increase sodium transport in both the intestines and the nephron, depending upon the state of sodium balance (5). An increase in extracellular fluid volume increases the production of dopamine and an increase in intracellular sodium increases the activity of dopamine receptors (6,7). Products of the fermentation of nutrients by gut microbiota can also influence blood pressure by regulating expenditure of energy, intestinal metabolism of catecholamines, and gastrointestinal and renal ion transport, and thus, salt sensitivity of blood pressure. Dr. Jose suggests that enterokines produced by the stomach, such as gastrin, can increase the renal production of dopamine and their receptors interact to inhibit renal sodium transport (8). Gastrin may be the enterokine released when stomach G-cells “taste” sodium. The gut microbiota can influence the enterochromaffin cell production of serotonin, dopamine, and norepinephrine that can influence the behavior of the host, termed brain gut microbiome axis and renal function, termed gastro-renal communication. As stated by Dr. Dominic Raj in his review “Gut microbiome in chronic kidney disease” a healthy adult harbors about 100 trillion bacteria, 10 times the number of human cells. About 1,000 bacterial species are harbored and the genome of the gut microbiota is 150 times larger than the human genome. Moreover, the gut microbiome has co-evolved with humans and that a symbiotic relationship has expanded the human metabolic and biosynthetic capabilities, well beyond what is encoded in the human genome. The microbiota in the gut, dominated to a large extent by Firmicutes and Bacteroidetes, and to a lesser extent by Actinobacteria, and Proteobacteria, constantly adapt to lifestyle modifications, such as diet and exercise. The gut microbiota can regulate about 10% of the host’s transcriptome, especially those genes related to immunity, cell proliferation, and metabolism. The gut microbiota have been shown to play a role in the development of conditions or diseases, such as obesity, insulin resistance, atherosclerosis, immune dysregulation, inflammation, susceptibility to infection, nephrolithiasis, and chronic kidney disease, among others. Dr. Raj states in his review that the major uremic toxins, p-cresol sulfate, indoxyl sulfate, and trimethylamine N-oxide, which are produced by the gut microbiome, contribute to progression of chronic kidney disease and associated cardiovascular disease (9). Dr. Jennifer Pluznik reports that a subset of gut microbial metabolites, known as short chain fatty acids (SCFA), act as ligands for host G protein-coupled receptors (G protein-coupled receptor 41 [Gpr41] and olfactory receptor 78 [Olfr78]). SCFA-mediated activation of Gpr41 and Olfr78 modulates blood pressure control, both by modulating renin secretion and vascular tone (10). Thus, the kidney can “smell” the metabolites produced by the gut microbiota. Sniffing and tasting (10, 11), and enterokines, among others, entail how the gastrointestinal tract and kidney communicate to regulate sodium balance and blood pressure.