Four distinct circuits are shown. (Green) Dietary choline is converted by gut microbes to trimethylamine (TMA), which undergoes oxidation in the liver to generate trimethylamine-N-oxide (TMAO). TMAO is renally cleared and has toxic cardiovascular effects. (Yellow) Dietary starch is converted by gut microbes to short chain fatty acids (SCFA, butyrate shown), which can then exert biologic effects as ligands for specific GPCRs, including in the kidney. (Blue) Dietary glutamine is converted by enterocytes to citrulline, which can then undergo enzymatic conversion in the kidney to arginine, which then exerts a range of biologic effects. Finally urea, which is synthesized primarily in the liver from excess ammonia derived from throughout the body (not shown) is excreted by the kidney.