基于16S rDNA序列分析胃肠外营养相关性胆汁淤积症早产儿肠道微生态和肠-肝轴的研究  

A Study on Intestinal Flora and Gut-liver Axis in Premature Infants with Parenteral Nutrition Associated Cholestasis Based on 16S rDNA Sequence Analysis

作　　者：杨秀芳[1] 曾柳钰 郑铠军[2] 邹梅玲 陈康[4] 施尚文 丁俊彩[1] 杨仙姬[1] YANG Xiufang;ZENG Liuyu;ZHENG Kaijun;ZOU Meiling;CHEN Kang;SHI Shangwen;DING Juncai;YANG Xianji(Neonatal Intensive Care Unit,Zhongshan City People’s Hospital,Zhongshan 528403,China;Department of Pediactrics,Zhongshan City People’s Hospital,Zhongshan 528403,China;Department of Maternal And Child Health,Zhongshan City People’s Hospital,Zhongshan 528403,China;Laboratory Center,Zhongshan City People’s Hospital,Zhongshan 528403,China;Guangdong Medical University,Zhongshan 524023,China)

机构地区：[1]中山市人民医院新生儿监护室,广东中山528403 [2]中山市人民医院儿科,广东中山528403 [3]中山市人民医院妇幼保健科,广东中山528403 [4]中山市人民医院检验中心,广东中山528403 [5]广东医科大学,广东中山524023

出　　处：《标记免疫分析与临床》2024年第3期482-490,共9页Labeled Immunoassays and Clinical Medicine

基　　金：中山市科技局立项(编号:2020B1045)。

摘　　要：目的旨在研究胃肠外营养相关性胆汁淤积症(PNAC)早产儿的肠道微生态特征和肠-肝轴在PNAC发病中的作用。方法采用前瞻性研究收集2020年5月1日至2022年12月31日在中山市人民医院新生儿监护室收治的早产儿,住院期间曾接收14d以上的胃肠外营养治疗。实验组为13例患有PNAC的早产儿,对照组为24例未患PNAC的早产儿。对两组患儿不同日龄的粪便中肠道菌群的DNA情况采用16S rDNA序列分析技术进行测定。同时检测两组早产儿不同日龄血清血炎症细胞因子包括降钙素原(PCT)、白细胞介素6(IL-6)水平和肝胆生化变化,通过统计学分析组间差异。结果实验组与对照组生后第1、7和14d的肠道菌门构成比的差异无统计学意义(χ_(D1)^(2)=0,χ_(D7)^(2)=1.06,χ_(D14)^(2)=6.98,P均>0.05),生后第30d的肠道菌门构成比的差异有统计学意义(χ_(D30)^(2)=16.29,P<0.05);对比两组出生后不同日龄肠道菌门的相对丰度,结果显示两组在生后第7d厚壁菌门、拟杆菌门和变形菌门相对丰度的差异无统计学意义(t值分别为0.69、2.00、2.00,P均>0.05);两组在生后第14d厚壁菌门、拟杆菌门、变形菌门相对丰度的差异均有统计学意义(t值分别为15.41、24.74、6.64,P均<0.05),两组在生后第30d厚壁菌门、拟杆菌门、变形菌门和放线菌门相对丰度的差异有统计学意义(t值分别为37.88、25.88、34.63、33.36,P均<0.05),提示在生后第14d和第30d实验组厚壁菌门相对丰度低于对照组,实验组拟杆菌门、变形菌门的相对丰度均高于对照组。对比两组动态的肝胆生化和炎症指标,结果显示,血清谷丙转氨酶(ALT)、总胆红素(T-BIL)、直接胆红素(D-BIL)、总胆汁酸(TBA)、γ-谷氨酰转肽酶(γ-GT)水平上,实验组在生后第14d、第30d和第60d血清ALT、T-BIL、D-BIL、TBA、γ-GT水平高于对照组,通过统计学分析,我们发现组间差异具有统计学意义(P均<0.05);实验组血清PCT、IL-6水平在�Objective The aim of this study was to investigate the intestinal microecological characteristics of premature infants with parenteral nutrition-associated cholestasis(PNAC)and the role of the gut-liver axis in the pathogenesis of PNAC.Methods This prospective study collected preterm infants admitted to the Neonatal Intensive Care Unit(NICU)of Zhongshan City People’s Hospital from May 1,2020 to December 31,2022.During hospitalization period,patients received parenteral nutrition for more than 14 days.13 premature infants with PNAC were enrolled as the experimental group,while 24 neonates without PNAC as the control group.16S rDNA sequence analysis was used to determine the DNA status of fecal intestinal flora of the two groups.The level of inflammatory cytokines,including procalcitonin(PCT),Interleukin 6(IL-6)levels and liver and hepatobiliary biochemistry in the serum at different age groups were detected.The differences between the two groups were statistically analyzed.Results The results of this study showed that there were no significant differences between the experimental group and the control groups in the proportion of intestinal flora on the 1^(st),7^(th) and 14^(th) days after birth(χ_(D1)^(2)=0,χ_(D7)^(2)=1.06,χ_(D14)^(2)=6.98,P>0.05).There was a significant difference in the composition of the intestinal flora at the 30th day after birth(χ_(D30)^(2)=16.29,P<0.05).The relative abundances of Firmicutes,Bacteroidetes and Proteobacteria were not significantly different between the two groups on the 7^(th) day after birth(t value:0.69,2.00,2.00,P>0.05).The relative abundances of Firmicutes,Bacteroidetes and Proteobacteria were significantly different between the two groups on the 14^(th) day after birth(t value:15.41,24.74,6.64,P<0.05).The relative abundance of Firmicutes,Bacteroidetes,Proteobacteria and Actinomycetes were also significantly different between the two groups on the 30^(th) day after birth(t value:37.88,25.88,34.63,33.36,P<0.05).The results showed that the relative abundance of Firmic

关 键 词：肠道菌群 炎症指标 早产儿 胃肠外营养 胆汁淤积 肠肝轴 

分 类 号：R575[医药卫生—消化系统]