Wagner Carsten A, Frey-Wagner Isabelle, Ortiz Alberto, Unwin Robert, Liabeuf Sophie, Suzumoto Yoko, Iervolino Anna, Stasi Alessandra, Di Marzo Vincenzo, Gesualdo Loreto, Massy Ziad A
Institute of Physiology and Zurich Kidney Center, University of Zurich, Switzerland.
Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
Nephrol Dial Transplant. 2025 Mar 13;40(Supplement_2):ii4-ii17. doi: 10.1093/ndt/gfae253.
Cognitive decline is frequently seen in patients with chronic kidney disease (CKD). The causes of cognitive decline in these patients are likely to be multifactorial, including vascular disease, uraemic toxins, blood-brain barrier leakage, and metabolic and endocrine changes. Gut dysbiosis is common in patients with CKD and contributes to the increase in uraemic toxins. However, the gut microbiome modulates local and systemic levels of several metabolites such as short-chain fatty acids or derivatives of tryptophan metabolism, neurotransmitters, endocannabinoid-like mediators, bile acids, hormones such as glucagon-like peptide 1 (GLP1) or cholecystokinin (CCK). These factors can affect gut function, immunity, autonomic nervous system activity and various aspects of brain function. Key areas include blood-brain barrier integrity, nerve myelination and survival/proliferation, appetite, metabolism and thermoregulation, mood, anxiety and depression, stress and local inflammation. Alterations in the composition of the gut microbiota and the production of biologically active metabolites in patients with CKD are well documented and are favoured by low-fiber diets, elevated urea levels, sedentary lifestyles, slow stool transit times and polypharmacy. In turn, dysbiosis can modulate brain function and cognitive processes, as discussed in this review. Thus, the gut microbiome may contribute to alterations in cognition in patients with CKD and may be a target for therapeutic interventions using diet, prebiotics and probiotics.
慢性肾脏病（CKD）患者常出现认知功能下降。这些患者认知功能下降的原因可能是多因素的，包括血管疾病、尿毒症毒素、血脑屏障渗漏以及代谢和内分泌变化。肠道微生物群失调在CKD患者中很常见，会导致尿毒症毒素增加。然而，肠道微生物群可调节多种代谢物的局部和全身水平，如短链脂肪酸或色氨酸代谢衍生物、神经递质、内源性大麻素样介质、胆汁酸、激素，如胰高血糖素样肽1（GLP1）或胆囊收缩素（CCK）。这些因素会影响肠道功能、免疫、自主神经系统活动以及脑功能的各个方面。关键领域包括血脑屏障完整性、神经髓鞘形成和存活/增殖、食欲、代谢和体温调节、情绪、焦虑和抑郁、应激以及局部炎症。CKD患者肠道微生物群组成的改变和生物活性代谢物的产生已有充分记录，低纤维饮食、尿素水平升高、久坐的生活方式、缓慢的粪便转运时间和多种药物治疗有利于这些改变。反过来，如本综述所讨论的，微生物群失调可调节脑功能和认知过程。因此，肠道微生物群可能导致CKD患者认知改变，可能是饮食、益生元和益生菌治疗干预的靶点。
