妊娠期糖尿病对母乳喂养的12周龄婴儿肠道菌群影响

doi:10.12372/jcp.2024.23e0806

摘要/Abstract

摘要：

目的比较妊娠期糖尿病（GDM）及正常孕妇的持续母乳喂养的12周龄婴儿肠道菌群的分布特点，以探索GDM对12周龄婴儿肠道菌群的影响。方法选择2016年6月—2019年12月入组的母亲及其随访至12周龄的母乳喂养的婴儿，依据母亲孕期血糖检测结果将母乳喂养婴儿分为GDM组（n=13）和对照组(n=27)。采集婴儿12周龄粪便，采用16S rDNA高通量测序技术对所有粪便样本进行检测，比较两组肠道菌群分布特点。采用Spearman相关分析法分析肠道菌群与孕期血糖、婴儿体重的相关性。结果共纳入40对研究对象，GDM组13对，对照组27对。两组的优势菌门均为放线菌门、厚壁菌门和变形菌门，GDM组的疣微菌门相对丰度高于对照组，差异有统计学意义（Z=2.233，P<0.05）。在属水平上，GDM组中肠道菌群优势菌属来自放线菌门和厚壁菌门，对照组中肠道菌群的优势菌属来自放线菌门、厚壁菌门和变形菌门。LEfSe差异分析结果显示，GDM组中疣微菌门/目/科、阿克曼氏菌、劳森氏菌、哈利真杆菌的丰度明显升高（LDA>2），而在对照组中芽孢杆菌目、孪生球菌属、丹毒梭菌属的丰度明显升高（LDA>2）。肠道优势菌群的门水平丰度与孕期血糖、12周龄婴儿体重均不相关（P>0.05）。结论孕期GDM对持续母乳喂养的12周龄婴儿肠道菌群构成产生一定的影响。

关键词: 妊娠糖尿病, 母乳喂养, 肠道菌群, 16SrDNA, 高通量测序

Abstract:

Objective To compare the distribution of gut microbiota in continuously breastfed 12 week-old infants whose mothers were diagnosed with and without gestational diabetes mellitus (GDM), and to further explore the effect of GDM on the gut microbiota of those infants. Methods The mothers enrolled between June 2016 and December 2019 and their breastfed infants who were followed up to 12 weeks of age were selected. The breastfed infants were divided into the GDM group (n=13) and the control group (n=27) according to the results of maternal blood glucose detection during pregnancy. Fecal samples were collected from infants at 12 weeks of age, and 16S rDNA high-throughput sequencing technology was used to detect all fecal samples, and gut microbiota distribution characteristics of the two groups were compared. Spearman correlation analysis was used to analyze the correlation between gut microbiota and blood glucose during pregnancy as well as infant weight. Results A total of 40 pairs of subjects were included, including 13 pairs in the GDM group and 27 pairs in the control group. The gut microbiota in the 2 groups consisted mainly of 3 phyla (Actinobacteria, Firmicutes, and Proteobacteria). The relative abundance of Verrucomicrobia in the GDM group was significantly higher than that in the control group (Z=2.233, P<0.05). At the genus level, the dominant genus in the GDM group came from Actinobacteria and Firmicutes, while in the control group came from Actinobacteria, Firmicutes and Proteobacteria. LEfSe analysis showed that the abundance of Verrucomicrobia, Akkermansia, Lawsonella and Eubacterium hallii were significantly increased in the GDM group, while the abundance of Bacillales, Gemella and Erysipelatoclostridium were significantly increased in the control group (LDA>2). The phylum-level abundance of gut microbiota was not correlated with blood glucose during pregnancy and infant weight at 12 weeks of age (P>0.05). Conclusions GDM during pregnancy had a certain effect on the gut microbiota composition of 12-week-old infants who were continuously breastfed.

Key words: gestational diabetes mellitus, breastfeeding, gut microbiota, 16S rDNA, high-throughput sequencing

赵永丽, 段一凡, 牛蓓, 张翠, 陈磊, 雍明媛, 刘长青. 妊娠期糖尿病对母乳喂养的12周龄婴儿肠道菌群影响[J]. 临床儿科杂志, 2024, 42(4): 305-310.

ZHAO Yongli, DUAN Yifan, NIU Bei, ZHANG Cui, CHEN Lei, YONG Mingyuan, LIU Changqing. Effect of gestational diabetes mellitus on gut microbiota of 12-week-old breastfed infants[J]. Journal of Clinical Pediatrics, 2024, 42(4): 305-310.

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组别	例数	孕妇年龄($\bar{x}±s$)/岁	孕前体质指数 ($\bar{x}±s$)/kg·m^-2	剖宫产比例	出生孕周($\bar{x}±s$)/周	12周龄体重[M(P₂₅~P₇₅)]/kg	孕期血糖[M(P₂₅~P₇₅)]/mmol·L^-1
GDM组	13	26.15±4.51	24.62±4.73	10/13	39.81±0.85	7.13(6.24~7.52)	5.21(5.08~5.55)
对照组	27	26.41±3.83	24.11±3.34	15/27	39.37±1.09	7.21(6.14~7.60)	4.37(4.14~4.54)
统计量 P		t=0.19 0.854	t=0.39 0.699	χ²=2.13 0.435	t=1.29 0.206	Z=0.09 0.927	Z=5.05 <0.0001

组别	例数	Alpha多样性指数
组别	例数	Observed Species	Goods coverage	Shannon	Simpson	Chao1
GDM组	13	140.2±14.83	1.00±0.00	2.53±0.56	0.65±0.13	178.9±26.27
对照组	27	152.0±23.69	1.00±0.00	2.74±0.63	0.71±0.13	186.9±32.69
t值 P		1.65 0.108	0.31 0.762	1.01 0.320	1.22 0.230	0.77 0.444

组别	例数	Actinobacteria ($\bar{x}±s$)	Firmicutes [M(P₂₅~P₇₅)]	Proteobacteria [M(P₂₅~P₇₅)]	Bacteroidetes [M(P₂₅~P₇₅)]	Verrucomicrobia [M(P₂₅~P₇₅)]
GDM组	13	46.27±27.04	23.87(18.73~36.14)	11.29(3.07~33.32)	0.16(0.09~0.25)	0.00(0.01~0.07)
对照组	27	45.46±23.23	29.84(14.17~35.61)	5.37(2.51~16.43)	0.13(0.08~5.48)	0.00(0.00~0.02)
统计量 P		t=0.10 0.922	Z=0.49 0.624	Z=0.49 0.624	Z=0.38 0.707	Z=2.23 0.026

优势菌群	孕期血糖		12周龄婴儿体重
优势菌群	r	P	r	P
Actinobacteria	0.144	0.375	-0.092	0.585
Firmicutes	-0.128	0.433	0.205	0.212
Proteobacteria	-0.025	0.880	0.102	0.543
Bacteroidetes	0.069	0.673	-0.041	0.806
Verrucomicrobia	-0.084	0.605	0.083	0.621