Gut Microbiome-Derived Short-Chain Fatty Acids in Glomerular Protection and Modulation of Chronic Kidney Disease Progression.

Chronic kidney disease (CKD) is a progressive disorder that is characterized by the gradual loss of kidney function, often leading to end-stage renal failure. Recent research has highlighted the role of gut dysbiosis and its metabolic byproducts in the pathogenesis of CKD, with a particular focus on short-chain fatty acids (SCFAs). SCFAs, including acetate, propionate, and butyrate, are primarily produced by the fermentation of dietary fibers by the gut microbiota and are known for their systemic anti-inflammatory and immunomodulatory properties. In CKD, gut dysbiosis results in a reduction in SCFA-producing bacteria and an increase in uremic toxin-producing microorganisms, contributing to systemic inflammation, oxidative stress, and renal fibrosis. The depletion of SCFAs has been shown to exacerbate glomerular injury, whereas their presence supports integrity of the glomerular barrier and confers protection against damage. These protective effects are mediated by several mechanisms, including the modulation of immune responses, preservation of epithelial barrier function, and activation of specific receptors, such as G protein-coupled receptor 41 (GPR41), GPR43, and GPR109A. The present review provides a comprehensive overview of current understanding of SCFA-mediated pathways in glomerular protection during CKD progression. It highlights the therapeutic potential of targeting the gut-kidney axis to mitigate CKD progression by examining the complex interplay between gut microbiota and disease development, with a particular focus on strategies to protect the glomerular structure and function.