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儿童功能性便秘肠道菌群结构和功能预测分析

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目的 研究功能性便秘(functional constipation,FC)患儿肠道菌群结构与功能的变化,探讨其可能的病理生理机制.方法 采用回顾性病例对照研究方法,收集、分析于2018年3月—2019年6月就诊于上海市儿童医院(上海交通大学医学院附属儿童医院)或常州市第七人民医院便秘门诊并确诊为FC的患儿资料,纳入FC组.对照组为同期于医院儿保科进行健康体检时经调查问卷显示无胃肠道症状且近两周内无服药史、无重大疾病史的健康儿童.分析两组肠道菌群多样性、菌群结构和菌群功能的差异.应用Shannon指数、Chao指数、Ace指数进行计算、评估肠道菌群α多样性.应用PCoA分析计算、评估肠道菌群β多样性.在门、目、科、属水平分析两组菌群结构差异.菌群功能通过肠道菌群KEGG功能预测进行分析.结果 FC组患儿74例,其中男36例、女38例,年龄为(34.66±22.50)个月.对照组儿童30名,其中男13名、女17名,年龄为(40.87±35.46)个月.两组间年龄、性别构成的差异无统计学意义(P=0.736、0.623).FC组Shannon指数、Chao指数、Ace指数得分均显著低于对照组(P=0.02或P<0.01),提示FC组肠道菌群的物种多样性和物种丰度均较低.两组共存在1 707个操作分类单元(OTU),其中420个为FC组和对照组共有,887个为对照组特有,400个为FC组特有.PCoA分析结果显示,FC组与对照组肠道菌群β多样性存在显著性差异(P<0.01).与对照组比较,FC组在门水平有3个菌门丰度增高,1个菌门丰度减低;FC组在目水平有6个菌目丰度增高,1个菌目丰度减低;FC组在科水平有12个菌科丰度增高,1个菌科丰度减低;FC组在属水平有19个菌属丰度增高,1个菌属丰度减低.肠道菌群KEGG功能预测分析提示,FC组与对照组间存在36项功能差异.与对照组相比,FC组磷酸戊糖途径、赖氨酸代谢等16个功能增强,而牛磺酸和亚牛磺酸代谢、色氨酸代谢等20个功能减退.结论 FC患儿与健康儿童间存在肠道菌群结构及其功能的差异,FC患儿肠道菌群多样性显著减低,刺激肠道蠕动的代谢产物可能减少,抑制肠道蠕动的代谢产物可能增多.
Structural and functional prediction analysis of microbiota in children with functional constipation
Objective To explore the structural and functional changes of gut microbiota and possible pathophysiological mechanism in children with functional constipation(FC).Methods This is a retrospective case-control study.The children diagnosed as FC at Children's Hospital of Shanghai or Changzhou No.7 People's Hospital from March 2018 to June 2019 were enrolled in FC group.And the children who underwent a health examination during the same period and had no gastrointestinal symptoms and history of taking medication or major illnesses in the past two weeks were selected as the control group.The diversity,structure and function of gut microbiota were compared between the two groups.The diversity of gut microbiota αwas evaluated by using Shannon index,Chao index,and Ace index.The diversity of gut microbiota β was assessed by PCoA analysis.The differences in microbial community structure at the phylum,order,family,and genus levels were analyzed between the two groups.KEGG function prediction was used to analyze the function of gut microbiota.Results There were 74 FC children(36 males and 38 females)with a mean age of(34.66±22.50)months in the FC group.There were 30 healthy children(13 males and 17 females)aged(40.87±35.46)months in the control group.There were no significant dierences in age or gender composition between the two groups(P=0.736,0.623).The scores of Shannon index,Chao index,and Ace index in the FC group were significantly lower than those in the control group(P<0.05).indicating gut microbial α diversity was significantly decreased in children with FC.There were 1 707 operational taxonomic units(OTU)in both groups.Of them,420 existed in both groups,887 were unique to the control group,and 400 were unique to the FC group.The PCoA analysis showed that there was significant difference in the diversity of gut microbiota β between two groups(P<0.01).Compared with the control group,the FC group showed increased abundance of three microbiotas and decreased abundance of one microbiota at the phylum level,increased abundance of 6 microbiotas and decreased abundance of one microbiota at the order level,increased abundance of 12 microbiotas and decreased abundance of one microbiota at the family level,and increased abundance of 19 microbiotas and decreased abundance of one microbiota at the genus level.KEGG function prediction showed that there were 36 functional differences between the FC group and the control group.Sixteen predicted microbial functions such as pentose phosphate pathway and lysine metabolism increased,while twenty functions such as taurine and hypotaurine metabolism,tryptophan metabolism decreased in children with FC.Conclusion There are differences in the structure and function of microbiota between children with FC and healthy children.Compared with healthy children,the diversity of microbiota was reduced in children with FC.Metabolites that stimulate intestinal peristalsis may decrease,while metabolites that inhibit intestinal peristalsis may increase in children with FC.

ChildFunctional constipationMicrobiota16S rRNA

牟娅妮、李世燕、徐莉、王怡仲、张婷、胡会

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200062 上海,上海市儿童医院(上海交通大学医学院附属儿童医院)消化科

中国科学院上海营养与健康研究所

常州市第七人民医院儿科

儿童 功能性便秘 肠道菌群 16S核糖体核糖核酸

国家自然科学基金上海市卫生健康委员会卫生行业临床研究专项面上项目

81870373202040481

2024

上海医学
上海市医学会

上海医学

CSTPCD
影响因子:0.582
ISSN:0253-9934
年,卷(期):2024.47(3)