慢性肾病患者肠道菌群特征及与微炎症因子水平的相关性
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摘要
目的 探究慢性肾病(CKD)患者肠道菌群特征及与微炎症因子水平的相关性。方法 选取2018年6月至2018年12月在莆田学院附属医院诊断及治疗的CKD患者25例(CKD组)和健康体检者25例(对照组),对两组研究对象进行肠道微生物检测,同时比较两组研究对象炎症因子水平,应用Pearson模型探究患者肠道微生态特征与炎症因子水平的相关性。结果 CKD组与对照组研究对象的肠道菌群构成具有显著差异,其中对照组双歧杆菌、乳杆菌、产甲酸草酸杆菌、草酸杆菌属、草酸杆菌科和普拉梭菌相对丰度高于CKD组,CKD组克雷伯菌属、大肠埃希菌属、肠杆菌科、瘤胃菌科、毛螺菌科、梭杆菌属和拟杆菌目相对丰度高于对照组,CKD组患者的IL-6、TNF-α、CRP和LPa水平显著高于对照组(t=3.876、4.177、2.236、3.354,P=0.000、0.000、0.030、0.002),Pearson相关性分析显示,双歧杆菌与IL-6、TNF-α水平呈明显负相关(r=-0.272、-0.482,P=0.009、0.002),乳杆菌与IL-6、LPa水平呈明显负相关(r=-0.438、-0.384,P=0.005、0.014),普拉梭菌与TNF-α水平呈明显负相关(r=-0.407,P=0.009),瘤胃菌科与IL-6、CRP水平呈明显正相关(r=0.477、0.508,P=0.002、0.001)。结论 CKD患者肠道菌群与健康人群存在明显差异,其中益生菌水平与炎症因子呈负相关,瘤胃菌科与炎症因子呈明显的正相关。
Objective To explore the characteristics of intestinal flora in patients with chronic kidney disease and its correlation with the level of micro-inflammatory factors. Methods Twenty five CKD patients(CKD group) and 25 healthy subjects(control group) diagnosed and treated in our hospital from June 2018 to December 2018 were selected, intestinal microorganism in the two groups was detected, and the levels of inflammatory factors were compared. Pearson model was used to explore the correlation between the intestinal microecological characteristics of patients and the levels of inflammatory factors. Results The composition of intestinal flora was significantly different between the two groups, the relative abundance of Bifidobacterium, Lactobacillus, Oxalobacillus formate, Oxalobacillus, Oxalobacteriaceae and Clostridium praecox in control group was higher than that of CKD group, the relative abundance of Klebsiella, Escherichia coli, Enterobacteriaceae, Rumen bacteriaceae, Trichospirillaceae, Clostridium and Bacteroides of CKD group was higher than that of control group, the levels of IL-6, TNF-α, CRP, and LPa in CKD group were significantly higher than that of control group(t=3.876, 4.177, 2.236, 3.354, P=0.000, 0.000, 0.030, 0.002). Correlation analysis showed that Bifidobacterium levels were negatively correlated with IL-6 and TNF-α levels(r=-0.272,-0.482;P=0.009,0.002), Lactobacillus was negatively correlated with IL-6 and LPa levels(r=-0.438,-0.384;P=0.005,0.014). There was a significant negative correlation between the level of TNF-α and Clostridium pulposus(r=-0.407,P=0.009).There was a significant positive correlation between Ruminococcaceae and IL-6 and CRP levels(r=0.477,0.508;P=0.002,0.001). Conclusion There are significant differences in intestinal flora between CKD patients and healthy people, the probiotics level is negatively correlated with inflammatory cytokines, and the Ruminococcaceae is positively correlated with inflammatory cytokines.
Objective To explore the characteristics of intestinal flora in patients with chronic kidney disease and its correlation with the level of micro-inflammatory factors. Methods Twenty five CKD patients(CKD group) and 25 healthy subjects(control group) diagnosed and treated in our hospital from June 2018 to December 2018 were selected, intestinal microorganism in the two groups was detected, and the levels of inflammatory factors were compared. Pearson model was used to explore the correlation between the intestinal microecological characteristics of patients and the levels of inflammatory factors. Results The composition of intestinal flora was significantly different between the two groups, the relative abundance of Bifidobacterium, Lactobacillus, Oxalobacillus formate, Oxalobacillus, Oxalobacteriaceae and Clostridium praecox in control group was higher than that of CKD group, the relative abundance of Klebsiella, Escherichia coli, Enterobacteriaceae, Rumen bacteriaceae, Trichospirillaceae, Clostridium and Bacteroides of CKD group was higher than that of control group, the levels of IL-6, TNF-α, CRP, and LPa in CKD group were significantly higher than that of control group(t=3.876, 4.177, 2.236, 3.354, P=0.000, 0.000, 0.030, 0.002). Correlation analysis showed that Bifidobacterium levels were negatively correlated with IL-6 and TNF-α levels(r=-0.272,-0.482;P=0.009,0.002), Lactobacillus was negatively correlated with IL-6 and LPa levels(r=-0.438,-0.384;P=0.005,0.014). There was a significant negative correlation between the level of TNF-α and Clostridium pulposus(r=-0.407,P=0.009).There was a significant positive correlation between Ruminococcaceae and IL-6 and CRP levels(r=0.477,0.508;P=0.002,0.001). Conclusion There are significant differences in intestinal flora between CKD patients and healthy people, the probiotics level is negatively correlated with inflammatory cytokines, and the Ruminococcaceae is positively correlated with inflammatory cytokines.
引文
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[2] Liu M,Li XC,Lu L,et al.Cardiovascular disease and its relationship with chronic kidney disease[J].Eur Rev Med & Pharmacolog Sci,2014,18(19):2918-2926.
[3] Shikata K,Makino H.Microinflammation in the pathogenesis of diabetic nephropathy[J].J Diabetes Investig,2013,4(2):142-149.
[4] Duran-Salgado MB,Rubio-Guerra AF.Diabetic nephropathy and inflammation[J].World J Diabetes,2014,5(3):393.
[5] Ramezani A,Massy ZA,Meijers B,et al.Role of the gut microbiome in uremia:A potential therapeutic target[J].Am J Kidney Dis,2016,67(3):483-498.
[6] Wing MR,Patel SS,Ramezani A,et al.Gut microbiome in chronic kidney disease[J].Exp Physiol,2016,19(4):471-477.
[7] Levin A,Stevens PE,Bilous RW,et al.Kidney disease:Improving global outcomes(KDIGO)CKD work group.KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease[J].Kidney Int,2013,3(Suppl):1-150.
[8] Jiang S,Xie S,Lv D,et al.Alteration of the gut microbiota in Chinese population with chronic kidney disease[J].Sci Rep,2017,7(1):2870.
[9] Ramezani A,Barrows IR,Raj DS.Electroacupuncture therapy for muscle atrophy in CKD:Is there a needle in the haystack[J].J Am Soc Nephrol,2015,26(3):510-512.
[10] Wu G,Wadgymar A,Wong G,et al.A cross-sectional immunosurveillance study of anti-EPO antibody levels in CRF patients receiving epoetin alfa in 5 Ontario Renal Centers[J].Am J Kidney Dis,2004,44(2):264-269.
[11] Wong MG,Pollock CA.Biomarkers in kidney fibrosis:Are they useful[J].Kidney Int,2014,4(Suppl):79-83.
[12] Meijers BK,Claes K,Bammens B,et al.p-Cresol and cardiovascular risk in mild-to-moderate kidney disease[J].Clin J Am Soc Nephrol,2010,5(7):1182-1189.
[13] Li XS,Obeid S,Klingenberg R,et al.Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes:A prognostic marker for incident cardiovascular events beyond traditional risk factors[J].Eur Heart J,2017,38(11):814.
[14] Mai AO,Singh R,Datta P,et al.Gut microbiota-dependent trimethylamine-N-oxide and serum biomarkers in patients with T2DM and advanced CKD[J].J Clin Med,2017,6(9):86.
[15] Tang WH,Wang Z,Kennedy DJ,et al.Gut microbiota-dependent trimethylamine N-oxide(TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease[J].Circ Res,2015,116(3):448-455.