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枸橼酸氢钾钠对尿酸结石患者肠道微生态的调节作用

Regulation of gut microecology in patients with uric acid stone by potassium sodium hydrogen citrate
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摘要 目的探讨枸橼酸氢钾钠溶石治疗对尿酸结石患者肠道菌群及其代谢产物的影响。方法前瞻性纳入苏州大学附属常熟医院2021年12月至2023年8月收治的40例尿酸结石(UAS)患者为UAS组,纳入同时期40例非结石(NS)健康对照者为NS组。对术后有多处残留或肾下盏难以清除的长径>6 mm的结石患者进行枸橼酸氢钾钠溶石治疗。对受试者进行血、尿生化检测,粪便16S核糖体RNA(rRNA)基因测序及短链脂肪酸(SCFAs)含量测定。利用SPSS 22.0、Mothur、R语言和Unparse软件对数据变量进行分析。结果UAS组血肌酐[92.50(30.25)μmol/L比(73.38±16.95)μmol/L,Z=-3.759,P<0.01]、血尿酸[(505.25±104.96)μmol/L比(365.75±91.69)μmol/L,t=6.331,P<0.01]高于NS组,UAS组尿pH值[5.50(1.00)比6.00(0.50),Z=-4.194,P<0.01]低于NS组。UAS组患者肠道菌群多样性的Ace指数[(181.25±57.38)比212.89(86.10),Z=-3.579,P<0.01]、Chao1指数(180.77±57.16比232.82±58.84,t=3.932,P<0.01)和Shannon指数(2.68±0.51比2.95±0.56,t=2.233,P<0.05)低于NS组。UAS组患者肠道中拟杆菌属菌[478.13(301.40)比300.06(204.28),Z=-2.365,P<0.05]和梭杆菌属[13.74(99.13)比0.42(4.43),Z=-4.344,P<0.01]丰度高于NS组,毛螺菌属[0.24(19.95)比9.89(25.19),Z=-2.732,P<0.01]、副萨特氏菌属[0.33(9.66)比3.77(17.53),Z=-2.142,P<0.05]和双歧杆菌属[0.43(1.17)比2.12(12.94),Z=-2.719,P<0.01]丰度低于NS组。15例UAS患者接受枸橼酸氢钾钠溶石治疗。治疗后患者血尿酸水平[(444.67±74.66)μmol/L比(520.67±101.23)μmol/L,t=2.340,P<0.05]、结石最长径[(4.27±1.16)mm比(9.87±3.52)mm,t=5.846,P<0.01]和结石平均CT值[(399.57±78.27)HU比(501.84±106.90)HU,t=2.990,P<0.01]低于治疗前,尿pH值[6.50(0.50)比5.00(0.50),Z=-4.608,P<0.01]高于治疗前。治疗后梭杆菌属丰度[3.98(53.76)比20.22(168.62),Z=-2.189,P<0.05]低于治疗前,Lachnoclostridium(48.91±22.41比26.63±18.30,t=-2.436,P<0.05)、副萨特氏菌属[(35.70±21.93)比0.16(16.91),Z=-2.087,P<0.05]丰度高于治疗前。治疗后患者粪便中丁酸水平高于治疗前(1017.05±438.37比669.94±258.97,t=-2.156,P<0.05)。结论尿酸结石患者具有独特的肠道微生态特征,枸橼酸氢钾钠溶石治疗能调节该类患者的肠道菌群及代谢产物。对肠道微生物及SCFAs的靶向调节有望提高药物治疗效果,预防结石复发。 Objective To examine the impact of potassium sodium hydrogen citrate(PSHC)on the composition of gut microbiota and its metabolites in patients with uric acid stone(UAS).Methods A total of 40 UAS patients were prospectively enrolled at Changshu Hospital Affiliated to Soochow University from December 2021 to August 2023,while 40 non-stone individuals were enrolled during the same period as the non-stone(NS)group.Patients with stones larger than 6 mm in length and those with multiple or difficult-to-remove subrenal calices after surgery received treatment with PSHC.The serum and urine were subjected to biochemical tests,while the stool underwent gene sequencing of 16S ribosomal RNA(rRNA)and determination of short chain fatty acids(SCFAs)content.Data variables were analyzed using SPSS 22.0,Mothur,R language,and Unparse software.Results The levels of creatinine[92.50(30.25)vs.(73.38±16.95)μmol/L,Z=-3.759,P<0.01]and uric acid[(505.25±104.96)vs.(365.75±91.69)μmol/L,t=6.331,P<0.01]were significantly higher in the UAS group than in the NS group,while urine pH level[5.50(1.00)vs.6.00(0.50),Z=-4.194,P<0.01]was significantly lower in the UAS group than in the NS group.Additionally,there was a decrease observed in the Ace index[(181.25±57.38)vs.212.89(86.10),Z=-3.579,P<0.01],Chao1 index(180.77±57.16 vs.232.82±58.84,t=3.932,P<0.01),and Shannon index(2.68±0.51 vs.2.95±0.56,t=2.233,P<0.05)of intestinal flora diversity in the UAS group when compared to the NS group.The abundances of Bacteroides[478.13(301.40)vs.300.06(204.28),Z=-2.365,P<0.05]and Fusobacterium[13.74(99.13)vs.0.42(4.43),Z=-4.344,P<0.01]were significantly higher in the UAS group than in the NS group,whereas those of Lachnospira[0.24(19.95)vs.9.89(25.19),Z=-2.732,P<0.01],Parasutterella[0.33(9.66)vs.3.77(17.53),Z=-2.142,P<0.05],and Bifidobacterium[0.43(1.17)vs.2.12(12.94),Z=-2.719,P<0.01]were significantly lower in the UAS group than in the NS group.A total of 15 UAS patients underwent PSHC dissolution therapy.After treatment,the uric acid level[(444.67±74.66)vs.(520.67±101.23)μmol/L,t=2.340,P<0.05],maximum stone diameter[(4.27±1.16)vs.(9.87±3.52)mm,t=5.846,P<0.01],and average CT value of stones[(399.57±78.27)vs.(501.84±106.90)HU,t=2.990,P<0.01]exhibited a significant decrease compared to pre-treatment levels.Additionally,urine pH[6.50(0.50)vs.5.00(0.50),Z=-4.608,P<0.01]demonstrated an elevation post-treatment.After the treatment,the abundances of Fusobacterium[3.98(53.76)vs.20.22(168.62),Z=-2.189,P<0.05]exhibited a decrease compared to pre-treatment,while those of Lachnoclostridium(48.91±22.41 vs.26.63±18.30,t=-2.436,P<0.05)and Parasutterella[(35.70±21.93)vs.0.16(16.91),Z=-2.087,P<0.05]demonstrated an increase.The level of butyric acid in stool increased after treatment compared to pre-treatment(1017.05±438.37 vs.669.94±258.97,t=-2.156,P<0.05).Conclusion UAS patients exhibit distinct intestinal microecological characteristics.Administration of PSHC can modulate gut microbiota and metabolites.Targeted regulation of gut microbiota and SCFAs holds great promise for enhancing the efficacy of pharmacological treatments and preventing stone recurrence.
作者 曹程 王李胜 陈创 顾宇伟 邵雨帆 章幸诞 范波 Cao Cheng;Wang Lisheng;Chen Chuang;Gu Yuwei;Shao Yufan;Zhang Xingdan;Fan Bo(Department of Urology,Changshu Hospital Affiliated to Soochow University(Changshu No.1 People’s Hospital),Changshu 215500,China)
出处 《中华实验外科杂志》 CAS 2024年第6期1168-1172,共5页 Chinese Journal of Experimental Surgery
基金 苏州市科技计划项目(SKJY2021008、SKY2023021) 常熟市"昆承英才"科技计划项目(KCH202302) 常熟市临床医学专家团队引进(CSYJTD202001)。
关键词 尿酸结石 枸橼酸氢钾钠 肠道菌群 短链脂肪酸 Uric acid stone Potassium sodium hydrogen citrate Gut microbiota Short chain fatty acids
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