慢性肾脏病5期患者的肠道菌群变化

doi:10.6040/j.issn.1671-7554.0.2019.002

摘要/Abstract

摘要： 目的通过16S rDNA测序技术探究慢性肾脏病5期(CKD5)患者与健康人体内肠道菌群构成的差异。方法研究入组健康对照组69例、慢性肾脏病5期非透析(CKD5-NHD)组24例、慢性肾脏病5期透析(CKD5-HD)组29例。通过16s rDNA测序技术研究CDK5组(CKD5-NHD组和CKD5-HD组)与健康对照组肠道菌群构成的差异,以LDA>2.0表示两组间生物群落存在显著差异。基于测序结果,应用宏基因组数据统计分析(STAMP)软件映射到京都基因与基因组百科全书(KEGG)和蛋白质直系同源簇(COG)数据库,研究CKD5患者肠道微生物群可能具有的功能。结果健康对照组中,拟杆菌门(Bacteroidetes)、γ-变形菌纲(Gammaproteobacteria)、肠杆菌科(Enterobacteriaceae)等占优势;在CKD-HD组中,肠球菌科(Enterococcaceae)、真细菌属(Eubacterium)、红杆菌科(Rhodobacteraceae)等丰度较高;而在CKD-NHD组中,放线菌门(Actinobacteria)、双歧杆菌属(Bifidobacterium)、红蝽菌目(Coriobacteriales)等为主要优势菌群。通过肠道微生物群功能预测发现,CKD5患者肠道失调的微生物群在脂质代谢、碳水化合物代谢、蛋白质及氨基酸代谢方面有着更活跃的表现。结论与健康人相比,CKD5患者肠道菌群发生显著变化。CKD5患者的紊乱肠道菌群能够影响机体物质代谢,并通过影响机体多种代谢及信号传导通路增加罹患并发症风险。

关键词: 慢性肾脏病, 透析, 非透析, 肠道微生态, 微生物16S rDNA测序

Abstract: Objective To explore the differences of gut microbiota composition between chronic kidney disease 5(CKD5)patients and healthy people. Methods The individuals were divided into the healthy control group(n=69), CKD5-none hemodialysis(NHD)group(n=24)and CKD5-hemodialysis(HD)group(n=29). 16S rRNA gene sequencing technology was used to analyze differences of the gut microbiota composition among the three groups. LDA>2.0 indicated significant differences in the biome between two groups. Based on the sequencing results, the function of intestinal microflora in CKD5 patients was studied by means of STAMP software mapping to KEGG and COG database. Results In the healthy control group, Bacteroidetes, Gammaproteobacteria, and Enterobacteriaceae were dominant. Enterococcaceae, Eubacterium, Rhodobacteraceae were high in CKD5-HD group, while Actinobacteria, Bifidobacterium, Coriobacteriales were dominant in the CKD5-NHD group. In the CKD5 patients, glycerolipid, carbohydrate, protein and amino acid metabolism activity was increased. Conclusion Significant differences were found in the composition and function of the gut microbiota between the CKD5 patients and healthy individuals. Imbalance of the gut micro- 山东大学学报 (医学版)57卷7期 -吕晨箫,等. 慢性肾脏病5期患者的肠道菌群变化 \=-biota in CKD5 patients may increased the risk of complications by influencing a variety of metabolic and signaling pathways.

Key words: Chronic kidney disease, Hemodialysis, None hemodialysis, Intestinal microbiota, Microbial 16S rDNA sequencing

中图分类号:

R574

吕晨箫,李洋,高颖,张群业,张磊,王尊松. 慢性肾脏病5期患者的肠道菌群变化[J]. 山东大学学报 (医学版), 2019, 57(7): 72-79.

LÜ Chenxiao, LI Yang, GAO Ying, ZHANG Qunye, ZHANG Lei, WANG Zunsong. Changes of intestinal microbiota in patients with chronic kidney disease 5[J]. Journal of Shandong University (Health Sciences), 2019, 57(7): 72-79.

参考文献

[1] Zhang L, Wang F, Wang L, et al. Prevalence of chronic kidney disease in China: a cross-sectional survey[J]. Lancet, 2012, 379(9818): 815-822.
[2] Kidney Disease: Improving Global Outcomes(KDIGO). KDIGO 2012 clinical practice guideline for evaluation and management of chronic kid- ney disease[J]. Kidney Int Suppl, 2013, 3(1): 1-150.
[3] Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions[J]. J Am Soc Nephrol, 2014, 25(4): 657-670.
[4] Noel S, Martinalingua MN, Bandapalle S, et al. Intestinal microbiota-kidney cross talk in acute kidney injury and chronic kidney disease[J]. Nephron Clin Pract, 2014, 127(1-4): 139-143.
[5] Richards EM, Pepine CJ, Raizada MK, et al. The gut, its microbiome, and hypertension[J]. Curr Hypertens Rep, 2017, 19(4): 36-47.
[6] Yang T, Santisteban MM, Rodriguez V, et al. Gut dysbiosis is linked to hypertension[J]. Hypertension, 2015, 65(6): 1331-1340.
[7] Duranton F, Cohen G, De Smet R, et al. Normal and pathologic concentrations of uremic toxins[J]. J Am Soc Nephrol, 2012, 23(7): 1258-1270.
[8] Lynch SV, Pedersen O. The human intestinal microbiome in health and disease[J]. N Engl J Mes, 2016, 375(24): 2369-2379.
[9] Wilck N, Matus MG, Kearney SM, et al. Salt-responsive gut commensal modulates TH17 axis and disease[J]. Nature, 2017, 551(7682): 585-589.
[10] Pluznick J. A novel SCFA receptor, the microbiota, and blood pressure regulation[J]. Gut Microbes, 2014, 5(2): 202-207.
[11] Mishima E, Fukuda S, Shima H, et al. Alteration of the intestinal environment by lubiprostone is associated with amelioration of adenine-induced CKD[J]. J Am Soc Nephrol, 2015, 26(8): 1787-1794.
[12] Yoshifuji A, Wakino S, Irie J, et al. Gut Lactobacillus protects against the progression of renal damage by modulating the gut environment in rats[J]. Nephrol Dial Transplant, 2016, 31(3): 401-412.
[13] Zeng YQ, Dai Z, Lu F, et al. Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease[J]. Oncotarget, 2016, 7(14): 17468-17478.
[14] 臧凯丽,江岩,孙勇,等.益生菌剂调整肠道疾病人群菌群结构丰度水平的研究[J].食品科学, 2018, 39(13): 131-143. ZANG Kaili, JIANG Yan, SUN Yong, et al. Probiotics modulate the structure and abundance of gut mircrobiota in populations with intestinal diseases[J]. Food Science, 2018, 39(13): 131-143.
[15] Hovind P, Rossing P, Tarnow L, et al. Remission of nephrotic-range albuminuria in type 1 diabetic patients[J]. Diabetes Care, 2001, 24(11): 1972-1977.
[16] 杨旭,焦睿,杨琳,等.基于新一代高通量技术的人类疾病组学研究策略[J].遗传, 2011, 33(8): 829-846. YANG Xu, JIAO Rui, YANG Lin, et al. New-generation high-throughput technologies based‘omics’research strategy in human disease[J]. Hereditas(Beijing), 2011, 33(8): 829-846.
[17] 刘玲雪. 基于16SrRNA基因的食源性致病菌的实时荧光PCR检测研究[D].济南:山东师范大学, 2016.
[18] Jiang XT, Peng X, Deng GH, et al. Illumina sequencing of 16S rRNA tag revealed spatial variations of bacterial communities in a mangrove wetland[J]. Microb Ecol, 2013, 66(1): 96-104.
[19] Durgan DJ, Ganesh BP, Cope JL, et al. Role of the gut microbiome in obstructive sleep apnea-induced hypertension[J]. Hypertension, 2016, 67(2): 469-474.
[20] Sun CY, Hsu HH, Wu MS. p-Cresol sulfate and indoxyl sulfate induce similar cellular inflammatory gene expressions in cultured proximal renal tubular cells[J]. Nephrol Dial Transplant, 2013, 28(1): 70-78.
[21] Wang L, Cao AL, Chi YF, et al. You-gui Pill ameliorates renal tubulointerstitial fibrosis via inhibition of TGF-β/Smad signaling pathway[J]. J Ethnopharmacol, 2015, 169(3): 229-238.
[22] Zhang W, Wang W, Yu H, et al. Interleukin-6 underlies angiotensin II-induced hypertension and chronic renal damage[J]. Hypertension, 2012, 59(1): 136-144.
[23] Barker SL, Pastor J, Carranza D, et al. The demonstration of αKlotho deficiency in human chronic kidney disease with a novel synthetic antibody[J]. Nephrol Dial Transplant, 2015, 30(2): 223-233.
[24] 马祥雪,王凤云,符竣杰,等.基于肠道菌群的中医健脾方剂作用机制的研究现状与思考[J].中国实验方剂学杂志, 2017, 23(5): 210-215. MA Xiangxue, WANG Fengyun, FU Junjie, et al. Research situation and thoughts of mechanism of traditional Chinese medicine spleen prescription based on intestinal Flora[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2017, 23(5): 210-215.
[25] Archer SD, McDonalid IR, Herbold CW, et al. Benthic microbial communities of coastal terrestrial and ice shelf Antarctic meltwater ponds[J]. Front Microbiol, 2015, 6:485-493. doi: 10.3389/fmicb.2015.00485.
[26] Chen Y, Yang F, Lu H, et al. Characterization of fecal microbial communities in patients with liver cirrhosis[J]. Hepatology, 2011, 54(2): 562-572.
[27] Pryde SE, Duncan SH, Hold GL, et al. The microbiology of butyrate formation in the human colon[J]. FEMS Microbiol Lett, 2002, 217(2): 133-139.
[28] Rose DJ, DeMeo MT, Keshavarzian A, et al. Influence of dietary fiber on inflammatory bowel disease and colon cancer: importance of fermentation pattern[J]. Nutr Rev, 2007, 65(2): 51-62.
[29] Guarner C, González-Navajas JM, Sánchez E, et al. The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation[J]. Hepatology, 2006, 44(3): 633-639.
[30] Pérez-Paramo M, Muñoz J, Albillos A, et al. Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites[J]. Hepatology, 2000, 31(1): 43-48.
[31] Wiest R, Garcia-Tsao G. Bacterial translocation(BT)in cirrhosis[J]. Hepatology, 2005, 41(3): 422-433.

相关文章 15

[1]	冯静静,张鲁伟,赵鹏,郭宁,田军,崔先泉. 彩色多普勒超声在终末期肾病患者自体动静脉内瘘术前评估及术后监测中的应用[J]. 山东大学学报 (医学版), 2018, 56(7): 65-69.
[2]	周苗,卞伟玮,柳晓涓,康凤玲,薛付忠,刘静. 嗜碱性粒细胞百分比与慢性肾脏病关系的回顾性队列研究[J]. 山东大学学报 (医学版), 2018, 56(3): 85-90.
[3]	周苗,夏同耀,孙爱玲,李明,申振伟,卞伟玮,蒋正,康凤玲,柳晓涓,薛付忠,刘静. 健康管理人群慢性肾脏病风险预测模型[J]. 山东大学学报（医学版）, 2017, 55(6): 98-103.
[4]	申振伟,季晓康,王庆莲,李洁,薛付忠,刘静. 非酒精性脂肪肝与慢性肾脏病关系的回顾性队列研究[J]. 山东大学学报（医学版）, 2016, 54(7): 43-49.
[5]	邱晶, 王丽莹, 张清霞, 曾算香, 王海燕. 延续性护理对腹膜透析出院患者自我管理行为的影响[J]. 山东大学学报（医学版）, 2014, 52(Z2): 156-157.
[6]	石正兰. 预见性护理干预减少血液透析患者急性左心衰竭发作的应用[J]. 山东大学学报（医学版）, 2014, 52(Z1): 182-182.
[7]	蔡宇, 张颖, 徐成. 维持性血液透析患者肾性骨病预防和护理[J]. 山东大学学报（医学版）, 2014, 52(Z1): 154-155.
[8]	王静, 李娟. 无肝素血液透析的疗效及护理体会[J]. 山东大学学报（医学版）, 2014, 52(Z1): 185-186.
[9]	梁波. 连续性静脉-静脉血液滤过治疗严重乳酸性酸中毒临床观察[J]. 山东大学学报（医学版）, 2014, 52(S2): 31-31.
[10]	赖小航, 杨沛华. 不同血液透析模式对外周血非对称性二甲基精氨酸及血压的影响[J]. 山东大学学报（医学版）, 2014, 52(S2): 25-26.
[11]	谭芳, 章厚芬. 不同途径深静脉置管在慢性肾衰竭患者血液透析中的应用[J]. 山东大学学报（医学版）, 2014, 52(S2): 134-135.
[12]	杨红兰. 慢性肾功能衰竭血液透析患者合并恶性肿瘤22例临床分析[J]. 山东大学学报（医学版）, 2014, 52(S1): 127-128.
[13]	李凤波, 高晓芳, 王小双. 基层医院维持性血液透析患者生存质量相关影响因素调查分析[J]. 山东大学学报（医学版）, 2014, 52(S1): 46-46.
[14]	姜祥品, 崔美玉, 孔祥雷, 许冬梅. 透析患者应用果糖二磷酸钠出现代谢性脑病1例[J]. 山东大学学报（医学版）, 2014, 52(8): 111-112.
[15]	梁素忍1，郭志玲1，胡昭2. 持续非卧床腹膜透析患者低T3综合征与大动脉僵硬度的关系[J]. 山东大学学报（医学版）, 2014, 52(1): 67-70.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed