16S rRNA第二代测序技术分析特发性身材矮小儿童肠道菌群构成的特征及相关发病机制研究

doi:10.16150/j.1671-2870.2021.02.006

摘要/Abstract

摘要：

目的:评估特发性身材矮小（idiopathic short stature,ISS）儿童与正常身高儿童的肠道菌群结构特征及组成差异,探究肠道菌群影响ISS发病的可能机制。方法:研究对象包括32名年龄4~8岁青春期前儿童,其中16例儿童被诊断为ISS（ISS组）,另16名为正常身高健康儿童（对照组）。选用细菌16S rRNA的V3~V4区作为目标片段,采用第二代测序技术检测研究对象粪便中的肠道菌群,分析比较2组间肠道菌群的多样性和丰度。结果:ISS组与对照组之间的肠道菌群组成存在显著差异,ISS组肠道菌群的多样性指数Chao1为1 109.85±435.23,显著低于对照组（1 485.68±334.51）（P=0.018）;ISS组肠道菌群的多样性指数Observed_species为946.98±374.93,显著低于对照组（1 217.69±289.66）（P=0.038）,提示ISS组肠道菌群的丰度降低。菌群分析发现,ISS组的柔嫩梭菌属（Faecalibac-terium）、真杆菌属（Eubacterium）相对丰度显著低于对照组（P<0.05）;在ISS组内,柔嫩梭菌属、真杆菌属与其身高标准差积分（standard deviation score,SDS）及胰岛素样生长因子1（insulin-like growth factor 1,IGF-1）SDS均呈显著正相关（r均>0.6,P<0.05）。结论:ISS组肠道菌群的丰度降低,菌群结构发生显著变化。ISS患儿肠道内的柔嫩梭菌属、真杆菌属通过短链脂肪酸（short-chain fatty acid,SCFA）使IGF-1合成减少,可能是致病原因之一。

关键词: 特发性身材矮小, 肠道菌群, 16S rRNA

Abstract:

Objective: To investigate structural characteristics of gut microbiome in idiopathic short stature (ISS) children and difference in gut microbiome between ISS and healthy children(HC) children, so as to explore the possible mechanism of action of gut microbiome on ISS. Methods: A total of 16 children aging from 4 to 8, including 16 ISS children (ISS group)and 16 HC (control group) were enrolled in the study. Flora of the collected feces were collected, and V3-V4 of bacterial 16S rRNA was sequenced with high-throughput sequencing. Diversity and abundance of gut microbiome between HC and ISS group were compared. Results: The structure of gut microbiome in ISS children were significantly different from HC children. The Chao1 (diversity index) of ISS group were lower than that of HC group (1109.85±435.23 vs. 1485.68±334.51) (P=0.018) as well as Observed_species index(946.98±374.93 vs. 1 217.69±289.66)(P=0.038), indicating decreased relative abundance of gut microbiome in ISS group. It’s also showed that the relative abundances of Faecalibacterium and Eubacterium were significantly lower in ISS group than HC group (P<0.05). In ISS group, both abundances of Faecalibacterium and Eubacterium were positively correlated with height-SDS and insulin-like growth factor 1(IGF1)-SDS（r>0.6, P<0.05）. Conclusions: For ISS, the abundance of gut microbiome decreases and the flora also experiences significant structural changes. Faecalibacterium and Eubacterium may decrease IGF-1 by short-chain fatty acid (SCFA), constituting a possible pathogenic mechanism for ISS.

Key words: Idiopathic short stature, Gut microbiome, 16S rRNA

中图分类号:

R725.8

李林, 安静静, 王俊祺, 王歆琼, 董治亚. 16S rRNA第二代测序技术分析特发性身材矮小儿童肠道菌群构成的特征及相关发病机制研究[J]. 诊断学理论与实践, 2021, 20(02): 149-154.

LI Lin, AN Jingjing, WANG Junqi, WANG Xinqiong, DONG Zhiya. The structure of gut microbiome in idiopathic short stature profiled by 16S rRNA second generation sequencing sequencing[J]. Journal of Diagnostics Concepts & Practice, 2021, 20(02): 149-154.

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参数	ISS组（n=16）	对照组(n=16)	P值
男性/女性	8/8	8/8	-
年龄（岁）	6.08±1.04	6.41±1.02	0.866
身高SDS	-2.34±0.29	0.52±0.27	<0.001
体质量指数SDS	0.04±0.74	0.81±0.75	0.007
靶身高（cm）	163.78±6.69	164.78±7.13	0.685