Gut Microbiome in Patients with Chronic Kidney Disease Stages 4 and 5: A Systematic Literature Review

This systematic review investigates the role of the gut microbiota in patients with advanced chronic kidney disease (CKD), specifically stages 4 and 5. Increasing evidence suggests that dysbiosis-an alteration in the normal balance of gut microbial populations-is not merely a secondary consequence of renal decline but a significant driver of disease progression. Such microbial imbalances are closely linked to a range of CKD-associated complications, including systemic inflammation, accumulation of uremic toxins, and heightened cardiovascular risk. Using PRISMA 2020 guidelines, we analyzed 87 peer-reviewed studies published between 2019 and 2025. The review revealed a consistent decline in beneficial microbes such as short-chain fatty acid-producing bacteria were markedly reduced, while populations of uremic toxin-generating microbes were notably increased. This microbial imbalance was associated with elevated concentrations of indoxyl sulfate and p-cresyl sulfate, heightened systemic inflammation, and impaired intestinal barrier integrity. Five conceptual frameworks-including the gut-kidney axis and endotoxemia-inflammation loop-were discussed. Ten microbiome assessment tools were reviewed, including 16S rRNA sequencing and LC-MS/MS for uremic toxin detection. Although probiotics, prebiotics, and synbiotics are gaining attention as potential therapeutic options, questions remain regarding their long-term efficacy and incorporation into standard clinical practice. Increasing scientific evidence underscores the gut microbiome's pivotal role in CKD progression and management, reinforcing the need for carefully designed, long-term interventions aimed at restoring a healthier microbial balance to support renal function.