柠檬酸铁作为磷酸盐结合剂可改变慢性肾脏病大鼠的肠道微生物组。
The Phosphate Binder Ferric Citrate Alters the Gut Microbiome in Rats with Chronic Kidney Disease.
机构信息
Division of Nephrology and Hypertension, Departments of Medicine (W.L.L., N.D.V., A.C.F.N., M.K.) and Molecular Biology and Biochemistry (W.E., J.P., K.W.), University of California, Irvine, California; Centre for Comparative Genomics and Evolutionary Bioinformatics Integrated Microbiome Resource, Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada (A.M.C., M.G.I.L.); and Department of Cardiology, Fukuoka University, Fukuoka, Japan (Y.S.)
Division of Nephrology and Hypertension, Departments of Medicine (W.L.L., N.D.V., A.C.F.N., M.K.) and Molecular Biology and Biochemistry (W.E., J.P., K.W.), University of California, Irvine, California; Centre for Comparative Genomics and Evolutionary Bioinformatics Integrated Microbiome Resource, Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada (A.M.C., M.G.I.L.); and Department of Cardiology, Fukuoka University, Fukuoka, Japan (Y.S.).
出版信息
J Pharmacol Exp Ther. 2018 Dec;367(3):452-460. doi: 10.1124/jpet.118.251389. Epub 2018 Oct 4.
In chronic kidney disease (CKD), the gut microbiome is altered and bacterial-derived uremic toxins promote systemic inflammation and cardiovascular disease. Ferric citrate complex is a dietary phosphate binder prescribed for patients with end-stage kidney disease to treat hyperphosphatemia and secondary hyperparathyroidism. Iron is an essential nutrient in both microbes and mammals. This study was undertaken to test the hypothesis that the large iron load administered with ferric citrate in CKD may significantly change the gut microbiome. Male Sprague-Dawley rats underwent 5/6 nephrectomy to induce CKD. Normal control and CKD rats were randomized to regular chow or a 4% ferric citrate diet for 6 weeks. Fecal and cecal microbial DNA was analyzed via 16S ribosomal RNA gene sequencing on the Illumina MiSeq system. CKD rats had lower abundances of Firmicutes and compared with normal rats and had lower overall gut microbial diversity. CKD rats treated with ferric citrate had improved hemoglobin and creatinine clearance and amelioration of hyperphosphatemia and hypertension. Ferric citrate treatment increased bacterial diversity in CKD rats almost to levels observed in control rats. The tryptophanase-possessing families Verrucomicrobia, Clostridiaceae, and Enterobacteriaceae were increased by ferric citrate treatment. The uremic toxins indoxyl sulfate and -cresyl sulfate were not increased with ferric citrate treatment. Verrucomicrobia was largely represented by , which has important roles in mucin degradation and gut barrier integrity. In summary, ferric citrate therapy in CKD rats was associated with significant changes in the gut microbiome and beneficial kidney and blood pressure parameters.
在慢性肾脏病（CKD）中，肠道微生物组发生改变，细菌衍生的尿毒症毒素促进全身炎症和心血管疾病。柠檬酸铁复合物是一种用于治疗终末期肾病患者高磷血症和继发性甲状旁腺功能亢进症的膳食磷酸盐结合剂。铁是微生物和哺乳动物的必需营养素。这项研究旨在检验假设，即在 CKD 中用柠檬酸铁给予大量铁负荷可能会显著改变肠道微生物组。雄性 Sprague-Dawley 大鼠接受 5/6 肾切除术以诱导 CKD。正常对照和 CKD 大鼠随机分为普通饮食或 4%柠檬酸铁饮食，持续 6 周。通过 Illumina MiSeq 系统对 16S 核糖体 RNA 基因进行粪便和盲肠微生物 DNA 分析。与正常大鼠相比，CKD 大鼠的厚壁菌门和Firmicutes 的丰度较低，且整体肠道微生物多样性较低。用柠檬酸铁治疗的 CKD 大鼠血红蛋白和肌酐清除率改善，高磷血症和高血压得到缓解。柠檬酸铁治疗增加了 CKD 大鼠的细菌多样性，几乎达到了对照组大鼠的水平。柠檬酸铁治疗增加了具有色氨酸酶的微生物家族厚壁菌门、梭菌科和肠杆菌科。柠檬酸铁治疗并没有增加尿毒症毒素吲哚硫酸酯和 - 对甲酚硫酸盐。厚壁菌门主要由具有重要作用的代表，其在粘蛋白降解和肠道屏障完整性中具有重要作用。总之，柠檬酸铁治疗 CKD 大鼠与肠道微生物组的显著变化以及有益的肾脏和血压参数相关。
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