Microbiota-derived metabolites and cognitive dysfunction in dialysis patients: mechanisms and targeted therapeutic strategies

Cognitive impairment (CI) in dialysis patients is a common and serious complication that significantly affects prognosis, with lack of effective treatment strategies. However, its mechanisms are still not fully clear, and effective treatment strategies are still limited. In recent years, more evidence has suggested that gut microbiota dysbiosis and changes in gut-derived metabolites may be involved in the development of CI in dialysis patients through the microbiota-gut-kidney-brain axis. Recent studies have shown that gut microbiota dysbiosis in dialysis patients may promote the progression of CI through several pathways. These include the accumulation of gut-derived uremic toxins, such as indoxyl sulfate (IS), p-cresyl sulfate (PCS), and Trimethylamine N oxide (TMAO), changes in bile acid metabolism; and the reduction of short-chain fatty acids (SCFAs) with neuroprotective effects. These changes may damage the intestinal barrier and the blood-brain barrier (BBB), and promote systemic inflammation, oxidative stress, and neuroinflammation. As a result, cognitive dysfunction in dialysis patients may be further aggravated. Therefore, targeting the gut microbiota has become a promising treatment direction. These strategies include dietary intervention, probiotics and related preparations, fecal microbiota transplantation (FMT), and targeted removal of uremic toxins and their derivatives. This review summarizes the gut microbiota composition associated with CI in dialysis patients, examines the molecular mechanisms of injury mediated by the microbiota-gut-brain-kidney axis, evaluates current microbiota-targeted interventions, and discusses future research directions for improving clinical prevention and treatment.