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ORIGINAL ARTICLE
Year : 2018  |  Volume : 131  |  Issue : 23  |  Page : 2792-2799

Relationship between Gut Microbiota and Phosphorus Metabolism in Hemodialysis Patients: A Preliminary Exploration


1 Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing 100034, China
2 Department of Biomedical Engineering, State Key Laboratory for Turbulence and Complex Systems, College of Engineering, and Centre for Quantitative Biology, Peking University, Beijing 100871, China

Correspondence Address:
Dr. Yu-Qing Chen
Renal Division, Department of Medicine, Peking University First Hospital, No. 8, Xishiku Street, Beijing 100034
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0366-6999.246059

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Background: Hyperphosphatemia is a risk factor associated with mortality in patients on maintenance hemodialysis. Gut absorption of phosphate is the major source. Recent studies indicated that the intestinal flora of uremic patients changed a lot compared with the healthy population, and phosphorus is an essential element of bacterial survival and reproduction. The purpose of this study was to explore the role of intestinal microbiota in phosphorus metabolism. Methods: A prospective self-control study was performed from October 2015 to January 2016. Microbial DNA was isolated from the stools of 20 healthy controls and 21 maintenance hemodialysis patients. Fourteen out of the 21 patients were treated with lanthanum carbonate for 12 weeks. Thus, stools were also collected before and after the treatment. The bacterial composition was analyzed based on 16S ribosomal RNA pyrosequencing. Bioinformatics tools, including sequence alignment, abundance profiling, and taxonomic diversity, were used in microbiome data analyses. Correlations between genera and the serum phosphorus were detected with Pearson's correlation. For visualization of the internal interactions and further measurement of the microbial community, SparCC was used to calculate the Spearman correlation coefficient with the corresponding P value between each two genera. Results: Thirteen genera closely correlated with serum phosphorus and the correlation coefficient was above 0.4 (P < 0.05). We also found that 58 bacterial operational taxonomic units (OTUs) were significantly different and more decreased OTUs were identified and seven genera (P < 0.05) were obviously reduced after using the phosphate binder. Meanwhile, the microbial richness and diversity presented downward trend in hemodialysis patients compared with healthy controls and more downward trend after phosphorus reduction. The co-occurrence network of genera revealed that the network complexity of hemodialysis patients was significantly higher than that of controls, whereas treatment with lanthanum carbonate reduced the network complexity. Conclusions: Gut flora related to phosphorus metabolism in hemodialysis patients, and improving intestinal microbiota may regulate the absorption of phosphate in the intestine. The use of phosphate binder lanthanum carbonate leads to a tendency of decreasing microbial diversity and lower network complexity.

 

 Abstract in Chinese

血液透析患者肠道菌群和磷代谢相关性的初步探讨

摘要

背景:高磷血症是维持性血液透析患者死亡相关的高危因素。肠道对磷的吸收是主要的来源。近期的研究显示尿毒症患者的肠道菌群与健康人群相比发生了较大改变。研究显示磷元素是细菌生存和繁殖的基本元素。该研究的主要目的是探讨血液透析患者肠道菌群在磷代谢中的作用。

方法:该研究为前瞻性自身对照研究,于2015年10月到2016年1月进行。维持性血液透析患者21人参加了碳酸镧降低磷负荷的治疗研究,其中14例透析患者完成了12周的治疗,7例因胃肠道反应和低钙血症中途退出。收集患者降磷前的粪便样本和14例完成治疗的患者治疗后的粪便标本,同时收集了20例健康志愿者的粪便标本。提取样本中的DNA,进行16S rRNA基因测序,对肠道菌群的分布情况和血磷之间的关系进行分析。分析过程包括数据拆分、长度过滤等数据预处理,以及OTU聚类、α多样性分析、Shannon指数计算、群落结构分析、菌门和菌属丰度分析。用Pearson相关性分析菌属与血清磷的相关性,P值小于0.05被认为是有意义的。为了进一步分析菌群内部之间的相互作用,SparCC用于计算菌属之间Spearman相关系数及对应的P值

结果:13种肠道菌和血磷显著相关,相关系数在0.4以上(P﹤0.05)。降磷治疗后,58个操作分类单元(OTU)有明显差异,减少的OTU比增加的OTU多;并且有7种菌属显著减少。健康人的菌群多样性有高于血透患者的趋势,同一批患者进行降磷后菌群多样性有进一步下降的趋势。血透患者菌属之间的网络复杂度高于健康人,患者降磷后菌属之间的网络复杂度降低。

结论:肠道菌群与血透患者磷代谢有相关性,改善肠道菌群有可能调节磷的肠道吸收。肠道磷结合剂的使用,使肠道菌群的多样性和网络复杂度下降



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