性早熟女童肠道菌群和抗生素耐药性的宏基因组分析

doi:10.16150/j.1671-2870.2022.01.011

摘要/Abstract

摘要：

目的： 分析性早熟女童肠道菌群的种属及所携带的抗性基因特征。目的： 收集21例性早熟女童[包括11例中枢性性早熟（central precocious puberty,CPP）女童、10例单纯性乳房早发育（premature thelarche,PT）]及8名健康对照（normal control,NC）女童的粪便样本,采用宏基因组测序技术分析组间样本肠道菌群的特征和差异,并重点分析抗性基因丰度分布。结果： 性早熟女童的肠道菌群在门、纲、目、科、属及种水平的组成及丰度上与健康女童间均存在差异。CPP组、PT组及NC组相对丰度排名前3位的肠道菌群分别为厚壁菌门（50.03%、37.73%及67.61%）、拟杆菌门（33.00%、43.26%及10.32%）、放线菌门（4.26%、4.22%及11.16%）。与NC组相比,性早熟组（CPP+PT）的拟杆菌门（P=0.034）丰度显著升高,厚壁菌门（P=0.006）及放线菌门（P<0.0001）丰度降低。CPP组、PT组及NC组分别发现有257种、273种和240种抗性基因。性早熟组（CPP+PT）抗性基因的种类明显多于NC组,其中四环素类及大环内酯类抗性基因丰度远高于NC组。结论： 与健康女童相比,性早熟女童的肠道菌群的分布存在明显差异,其携带抗性基因的种类明显高于健康女童,且抗性基因富集于四环素与大环内酯类,提示饮食、环境中的抗生素暴露影响了儿童肠道菌群分布,这可能与性早熟的发生相关。

关键词: 中枢性性早熟, 单纯性乳房早发育, 肠道菌群, 宏基因组, 抗性基因

Abstract:

Objective: To investigate the gut microbiota distribution and antibiotic resistant genes (ARGs) carrying- status in the girls with precocious puberty (PP). Methods: A total of 29 girls were enrolled in the study, including 21 girls with precocious puberty (PP) [11 girls with central precocious puberty (CPP group), 10 girls with premature thelarche (PT group)], and 8 age-matched healthy girls (NC group). The fecal samples were analyzed to explore difference in composition of gut microbiota and ARGs numbers between the PP (CPP+PT) and NC groups using shotgun metagenomic sequencing. Results: The composition and abundance of gut microbiota in the PP girls were different from the NC girls. The relative abundances of top three gut microbiota in CPP, PT and NC girls were 50.03%, 37.73% and 67.61% for Firmicutes, 33.00%, 43.26% and 10.32% for Bacteroidetes, and 4.26%, 4.22% and 11.16% for Actinobacteria. Compared with the NC girls, the PP girls had a significantly higher abundance of Bacteroidetes (P=0.034) and much lower abundance of Firmicutes (P=0.006) and Actinobacteria (P<0.000 1). It revealed that there were 257, 273 and 240 species of ARGs identified in the CPP, PT and NC girls, respectively. The PP girls had more ARGs types and higher abundance of tetracyclines and macrolide ARGs than the NC girls. Conclusions: Compared with the NC girls, the PP girls have a different distribution of gut microbiota and more species of ARGs enriching in tetracyclines and macrolides. It indicates that the dietary and environmental antibiotic exposure may influence the gut microbiota distribution in children, which may be associated with the pathogenesis of PP.

Key words: Central precocious puberty, Premature thelarche, Gut microbiota, Metagenomics, Antibiotic resistant genes

中图分类号:

R725

许飞, 尹明月, 王伟, 董治亚, 陆文丽, 余熠, 王歆琼, 王俊祺, 肖园. 性早熟女童肠道菌群和抗生素耐药性的宏基因组分析[J]. 诊断学理论与实践, 2022, 21(01): 52-61.

XU Fei, YIN Mingyue, WANG Wei, DONG Zhiya, LU Wenli, YU Yi, WANG Xinqiong, WANG Junqi, XIAO Yuan. Metagenomic analysis of gut microbiota and antibiotic resistome in girls with precocious puberty[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(01): 52-61.

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指标	CPP组（n=11）	PT组（n=10）	NC组（n=8）	P值
年龄（岁）	8.1±1.2	7.5±0.8	7.2±0.5	0.098
身高（cm）	133.2±12.1	127.1±7.8	122.9±4.0	0.062
体重（kg）	29.9±7.1	27.0±4.9	23.9±2.3	0.075
BMI（kg/m²）	16.6±2.3	16.6±2.1	15.9±1.7	0.687
靶身高（cm）	160.1±3.7	158.5±2.6	161.1±4.9	0.346
骨龄（years）	9.8±1.5	8.2±2.1	-	0.053
基线LH（IU/L）	1.9±2.0	0.6±1.1	-	0.016
LH峰值（IU/L）	9.6（6.1~21.5）	3.5（2.3~4.9）	-	<0.001
基线FSH（IU/L）	3.3（2.5~5.8）	2.6（1.3~3.0）	-	0.324
FSH峰值（IU/L）	8.5（7.4~16.7）	13.5（9.4~17.6）	-	0.032
LH/FSH	1.1（0.8~2.1）	0.2（0.2~0.4）	-	<0.001