Corte-Iglesias Viviana, Saiz Maria Laura, Andrade-Lopez Ana Cristina, Salazar Nuria, Bernet Cristian Ruiz, Martin-Martin Cristina, Borra Jesús Martinez, Lozano Juan-Jose, Aransay Ana M, Diaz-Corte Carmen, Lopez-Larrea Carlos, Suarez-Alvarez Beatriz
Translational Immunology, Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Asturias, Spain.
Kidney Disease Spanish Network, RICORS2040, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Nephrol Dial Transplant. 2024 Dec 20;40(1):133-150. doi: 10.1093/ndt/gfae118.
Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies.
SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease, and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD.
Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by tumour necrosis factor-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively, prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term.
Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.
短链脂肪酸（SCFAs），主要是乙酸盐、丙酸盐和丁酸盐，由肠道微生物群通过发酵人类宿主无法消化的复杂碳水化合物产生。它们影响肠道健康，并在远端水平上对包括肾脏疾病在内的几种疾病的病理生理学产生影响。
测量了不同疾病阶段的慢性肾脏病（CKD）患者（n = 54）的SCFA水平，并检查了其与肾功能和炎症参数的相关性。使用全基因组表达分析来分析丙酸盐和丁酸盐在炎症条件下肾小管细胞中触发的信号通路中的作用。最后，使用叶酸诱导的从急性肾损伤转变为CKD的临床前小鼠模型来分析这些微生物代谢产物在CKD发展中的预防和治疗潜力。
CKD患者粪便中的丙酸盐和丁酸盐水平随着疾病进展而逐渐降低，并且与血清肌酐、血尿素氮和估计肾小球滤过率等既定临床参数密切相关。丙酸盐和丁酸盐共同下调了103个与肿瘤坏死因子-α在肾小管细胞中触发的炎症过程和免疫系统激活相关的基因的表达。在体内，分别在损伤前或损伤后不久给予丙酸盐和丁酸盐，可预防并减缓损伤进展。这表现为肾损伤标志物减少、促炎和促纤维化标志物的表达降低以及肾功能的长期恢复。
丙酸盐和丁酸盐水平与CKD患者肾功能的逐渐丧失有关。在急性肾损伤的临床前模型中，早期给予这些SCFAs可预防疾病进展，表明它们独立于肠道微生物群具有治疗潜力。
