KU Leuven, Department of Nephrology and Department of Immunology and Microbiology, Laboratory of Nephrology, Leuven, Belgium.
Division of Nephrology, Medizinische Klinik and Poliklinik IV, Klinikum der LMU München-Innenstadt, München, Germany.
Nat Rev Nephrol. 2019 Sep;15(9):531-545. doi: 10.1038/s41581-019-0172-1. Epub 2019 Jun 26.
Environmental changes can induce diversity shifts within ecosystems that affect interactions between species. Similarly, the development of kidney disease induces shifts within the ecosystem of the intestinal microbiome, affecting host physiology and fitness. Renal failure itself, together with related changes in diet and medication, alters the microbiota and its secretome of micronutrients, nutrients and regulatory metabolites towards a phenotype characterized by the production of uraemic toxins, hence contributing to the clinical syndrome of uraemia and its complications. These alterations are associated with structural changes in the intestinal wall that impair barrier function and cause leakage of bacterial metabolites, bacterial wall products and live bacteria into the circulation. Thus, the intestinal microbiota represents a new therapeutic target to improve outcomes of chronic kidney disease (CKD), including symptoms of uraemia, metabolic changes, cardiovascular complications, aberrant immunity and disease progression. Initial interventional studies have shown promising effects of unselective probiotic preparations on kidney inflammation and uraemia in patients with CKD but longer-term studies are needed. Here, we take an ecological approach to understand the role of the intestinal microbiota in determining survival fitness in kidney disease.
环境变化会引起生态系统内的多样性变化,从而影响物种间的相互作用。同样,肾脏疾病的发展会引起肠道微生物组生态系统内的变化,影响宿主的生理和健康。肾衰竭本身以及相关的饮食和药物变化会改变微生物群及其微量营养素、营养物和调节代谢物的分泌组,朝着产生尿毒症毒素的表型发展,从而导致尿毒症及其并发症的临床综合征。这些改变与肠道壁的结构变化有关,这些结构变化会损害屏障功能,并导致细菌代谢物、细菌壁产物和活菌泄漏到循环中。因此,肠道微生物群代表了改善慢性肾脏病 (CKD) 结局的一个新的治疗靶点,包括尿毒症症状、代谢变化、心血管并发症、异常免疫和疾病进展。初步的干预性研究表明,非选择性益生菌制剂对 CKD 患者的肾脏炎症和尿毒症有一定的治疗效果,但需要进行更长期的研究。在这里,我们采用生态学方法来理解肠道微生物群在决定肾脏疾病中生存适应度方面的作用。