Wakino Shu, Hasegawa Kazuhiro, Tamaki Masanori, Minato Masanori, Inagaki Taizo
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.
Nutrients. 2025 Jun 9;17(12):1961. doi: 10.3390/nu17121961.
Chronic kidney disease (CKD) has a high prevalence worldwide, with an increasing incidence. One of the mechanisms of CKD progression involves a disordered inter-organ relationship between the kidneys and the intestine, known as the kidney-gut axis. In CKD, two pathological gut conditions-disturbed gut microbiota composition called uremic dysbiosis and leaky gut-contribute to the progression of CKD. Dysbiosis is associated with the increased production of gut-derived uremic toxins, leaky gut, and chronic systemic inflammation, leading to worsening uremia, which in turn aggravates the gut condition. This vicious cycle should be a target of the therapeutic strategy against CKD. The modulation of uremic dysbiosis, including prebiotics, probiotics, and synbiotics, has been a typical treatment approach, although clinical evidence for their efficacy has been insufficient. Some non-antibiotic drugs have an impact on human gut bacteria that are believed to play a role in their clinical efficacy on kidney function. Nutrition therapies, including a low-protein diet, dietary fiber, a Mediterranean diet, and whole grains, positively influence gut microbiota composition and have been linked to a decreased risk of CKD. Novel strategies are currently being explored, involving the use of postbiotics, microbiome sequencing techniques, and fecal microbiota transplantation, although clinical application remains to be tested. Human trials investigating the above-mentioned interventions remain inconclusive due to several limitations, including dietary variability and genetic factors. Future research should focus on the development of more effective probiotics, prebiotics, and microbial metabolism-modifying drugs, not only for CKD but for other systemic diseases as well.
慢性肾脏病（CKD）在全球范围内具有较高的患病率，且发病率不断上升。CKD进展的机制之一涉及肾脏与肠道之间器官间关系紊乱，即所谓的肾-肠轴。在CKD中，两种肠道病理状况——称为尿毒症菌群失调的肠道微生物群组成紊乱和肠道通透性增加——促进了CKD的进展。菌群失调与肠道源性尿毒症毒素产生增加、肠道通透性增加和慢性全身炎症相关，导致尿毒症恶化，进而加重肠道状况。这种恶性循环应成为CKD治疗策略的目标。调节尿毒症菌群失调，包括使用益生元、益生菌和合生元，一直是典型的治疗方法，尽管其疗效的临床证据不足。一些非抗生素药物对人体肠道细菌有影响，据信这些细菌在其对肾功能的临床疗效中发挥作用。营养疗法，包括低蛋白饮食、膳食纤维、地中海饮食和全谷物，对肠道微生物群组成有积极影响，并与CKD风险降低有关。目前正在探索新的策略，包括使用后生元、微生物组测序技术和粪便微生物群移植，尽管其临床应用仍有待测试。由于包括饮食变异性和遗传因素在内的若干限制，对上述干预措施的人体试验仍无定论。未来的研究应侧重于开发更有效的益生菌、益生元和微生物代谢调节药物，不仅用于CKD，也用于其他全身性疾病。
