Impact of gut microbiota in chronic kidney disease: natural polyphenols as beneficial regulators

Chronic kidney disease (CKD) poses a severe health risk with high morbidity and mortality, profoundly affecting patient quality of life and survival. Despite advancements in research, the pathophysiology of CKD remains incompletely understood. Growing evidence links CKD with shifts in gut microbiota function and composition. Natural compounds, particularly polyphenols, have shown promise in CKD treatment due to their antioxidant and anti-inflammatory properties and their ability to modulate gut microbiota. This review discusses recent progress in uncovering the connections between gut microbiota and CKD, including microbiota changes across different kidney diseases. We also examine metabolite alterations,such as trimethylamine-N-oxide, tryptophan derivatives, branched-chain amino acids, short-chain fatty acids, and bile acids,which contribute to CKD progression. Further, we outline the mechanisms through which polyphenols exert therapeutic effects on CKD, focusing on signaling pathways like nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), phosphatidylin-ositol-3-kinase (PI3K)/protein kinase B (Akt), and toll like receptors (TLR), as well as their impact on gut microbiota. Lastly, we consider how dietary polyphenols could be harnessed as bioactive drugs to slow CKD progression. Future research should prioritize multi-omics approaches to identify patients who would benefit from polyphenolic interventions, enabling personalized treatment strategies to enhance therapeutic efficacy.