A spotlight on the inflammatory role of uremic toxins in the dysbiosis–CKD axis: a review

There is growing evidence that gut-derived metabolites activate specific signaling pathways that lead to renal inflammation and injury, suggesting that the gut-kidney axis plays a significant role in the inflammatory processes that underlie chronic kidney disease (CKD). Alterations in the gut microbiota in CKD patients known as dysbiosis increases the production of uremic toxins such as p-cresyl sulfate, indoxyl sulfate and Trimethylamine N-oxide. These toxins trigger pro-inflammatory signaling pathways in renal tubular cells by initiating a series of inflammatory events, such as immune dysregulation, oxidative stress, and endotoxemia. As a result, cytokines like TNF-α, IL-6, and IL-1β are expressed more frequently, creating a chronic inflammatory environment that increase kidney damage and the progression of CKD. Emerging therapeutic strategies that alter gut microbiota composition, such as prebiotics, probiotics, dietary fiber, and fecal microbiota transplantation, have demonstrated promise in decreasing the burden of inflammation-inducing toxins. As research reveals new linkages between microbial metabolites and inflammatory signaling in CKD, addressing uremic toxin-mediated inflammation could revolutionize disease management. Understanding these interrelated signaling systems provides a more detailed understanding of how gut microbes influence renal inflammation at the molecular level. The aim of this review is to investigate the underlying signaling pathways by which gut-renal dysbiosis induces inflammation in CKD. The review attempts to guide the development of targeted treatment approaches that can reduce the inflammatory load and slow the progression of CKD by examining the mechanisms in which gut-derived uremic toxins alter oxidative stress, immunological responses, and inflammatory cascades. Not applicable.