Figure 1 .

The gut-kidney axis in diabetic nephropathy (DN)

With the manifestation of renal dysfunction, (1) glomerular filtration rate (GFR) decreases with podocyte damage and death, and (2) uremic toxins accumulate in the circulation and destroy the homeostasis of the intestinal microbiota, namely, dysbiosis. Subsequently, (3) pathogens utilizing nitrogenous waste are increased at the expense of fewer probiotics. (4) Short-chain fatty acid (SCFA) production decreases, while the levels of typical uremic toxins, such as p-cresyl sulfate (PCS), indolyl sulfate (IS), phenyl sulfate (PS) and trimethylamine N-oxide (TMAO), are increased, and (5) ultimately deteriorates DN. In addition, (6) changes in the intestinal microenvironment result in increased intestinal permeability, leading to the leakage of bacterial components such as lipopolysaccharides. (7) These endotoxins bind to signaling molecules such as toll-like receptors (TLRs) to recruit inflammatory cytokines and (8) cause chronic systemic inflammation in the kidney.