Article(id=1321170537762631774, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1321170430187130949, articleNumber=null, orderNo=null, doi=10.11847/zgggws1145737, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1724947200000, receivedDateStr=2024-08-30, revisedDate=1726070400000, revisedDateStr=2024-09-12, acceptedDate=1730995200000, acceptedDateStr=2024-11-08, onlineDate=1792921202363, onlineDateStr=2026-10-25, pubDate=1739116800000, pubDateStr=2025-02-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792921202363, onlineIssueDateStr=2026-10-25, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792921202363, creator=13701087609, updateTime=1792921202363, updator=13701087609, issue=Issue{id=1321170430187130949, tenantId=1146029695717560320, journalId=1319373219989389464, year='2025', volume='41', issue='2', pageStart='129', pageEnd='256', issueExtLink='null', onlineDate='null', pubDate='1739116800000', pubDateStr='2025-02-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792921176716, creator='13701087609', updateTime=1792921176716, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=212, endPage=216, ext={EN=ArticleExt(id=1321170538135924831, articleId=1321170537762631774, tenantId=1146029695717560320, journalId=1319373219989389464, language=EN, title=Effect of gestational diabetes mellitus on the gut microbiota of male and female infants at 12 weeks: a hospital-based follow-up study, columnId=1320427686514770171, journalTitle=Chinese Journal of Public Health, columnName=Survey and Report, runingTitle=null, highlight=null, articleAbstract=
Objective

To study the effects of gestational diabetes mellitus (GDM) on the gut microbiota of male and female infants.

Methods

From June 2016 to December 2019, 913 singleton pregnant women (aged 18–45 years) attending prenatal examinations at a county hospital in Hebei province were enrolled in the study. Information on prenatal examinations and laboratory test results were collected, and their offspring were followed up to 12 weeks of age. Fresh fecal samples were collected from the infants as samples. Based on the results of two maternal fasting blood glucose tests (at 12 and 24 weeks of gestation), a total of 48 healthy full-term infants with no history of antibiotic use were divided into two groups: the GDM group, in which the mothers had fasting blood glucose levels ≥ 5.1 mmol/L on both tests, and the control group, in which the mothers had normal fasting blood glucose levels on both tests. 16S rDNA sequencing was performed using high-throughput sequencing technology.

Results

Of the 16 infants in the GDM group, 10 were male and 6 were female, while of the 32 infants in the control group, 17 were male and 15 were female. In the female infants, the Chao1 index of gut microbiota was lower in the GDM group than in the control group (t= –3.34, P< 0.01). LEfSe analysis showed that the highly expressed gut microbiota in the male infants of the GDM group were Lactobacillaceae and Lactobacillus, while in the female infants, it was Carnobacteriaceae. In male infants, the relative abundance of Lactobacillus was higher in the GDM group than in the control group (Z=4.66, P =0.03), and the relative abundance of Erysipelatoclostridium was lower in the GDM group than in the control group (Z= –4.45, P= 0.04). In female infants, the relative abundances of Lactobacillus and Rothia were lower in the GDM group than in the control group (Z= –10.19, P <0.01; Z= –4.42, P=0.04). There were no statistically significant gender differences in the gut microbiota at the phylum and genus level (all P > 0.05).

Conclusions

Compared with the offspring of mothers with healthy pregnancies, the gut microbiota richness of female infants of mothers with GDM was reduced, which may also affect the relative abundance of Lactobacillus and Rothia in female infants. In addition, the gut microbiota richness of female infants was lower than that of male infants, but gender had no significant effect on the composition of the infant gut microbiota.

, authors=Cui ZHANG1, Yongli ZHAO1, Yifan DUAN2, Yuanyuan ZHOU1, Bei NIU1, Changqing LIU1, authorsList=Cui ZHANG, Yongli ZHAO, Yifan DUAN, Yuanyuan ZHOU, Bei NIU, Changqing LIU, authorCompany=null, correspAuthors=Changqing LIU, authorNote=null, correspAuthorsNote=
LIU Changqing, E-mail:
, copyrightStatement=Copyright © 2025 Chinese Journal of Public Health. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1321170541994684525, articleId=1321170537762631774, tenantId=1146029695717560320, journalId=1319373219989389464, language=CN, title=妊娠期糖尿病对不同性别子代婴儿肠道菌群的影响, columnId=1320427686770622717, journalTitle=中国公共卫生, columnName=调查报告与分析, runingTitle=null, highlight=null, articleAbstract=
目的

探讨母亲妊娠期糖尿病(GDM)对不同性别子代婴儿肠道菌群的影响。

方法

于2016年6月—2019年12月,将在河北省某县医院产检的孕妇为研究对象,共913名,收集孕检和实验室检查结果相关信息,并随访其子代至12周龄,采集子代婴儿的新鲜粪便作为样本。根据孕妇2次(孕12周和孕24周)的空腹血糖检测结果进行分组,将母亲孕期2次空腹血糖结果均≥5.1 mmol/L的婴儿纳入到GDM组;将母亲孕期2次空腹血糖结果均正常的婴儿纳入到对照组。应用高通量测序技术进行16S rDNA测序检测分析。

结果

共有48名婴儿纳入到本研究,其中GDM组16人,对照组32人。女婴中GDM组的肠道菌群Chao1指数低于对照组(t=–3.34,P<0.01)。LEfSe分析显示男婴中GDM组高表达的肠道菌群为乳杆菌科/属(Lactobacillaceae、Lactobacillus),女婴中GDM组高表达的为肉杆菌科(Carnobacteriaceae)。男婴中,GDM组乳杆菌属(Lactobacillus)的相对丰度高于对照组(Z=4.66,P=0.03),丹毒杆菌属(Erysipelatoclostridium)的相对丰度低于对照组(Z= –4.45,P=0.04);女婴中,GDM组乳杆菌属(Lactobacillus)和罗氏菌属(Rothia)的相对丰度低于对照组(Z= –10.19,P<0.01;Z= –4.42,P=0.04)。门水平、属水平肠道菌群在不同性别间的差异无统计学意义(均P>0.05)。

结论

与母亲妊娠期健康的子代相比,母亲GDM子代女婴肠道菌群的丰富度降低,还可能影响子代女婴乳杆菌属(Lactobacillus)、罗氏菌属(Rothia)的相对丰度。另外女婴肠道菌群的丰富要低于男婴,但性别对婴儿肠道菌群构成影响不明显。

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张翠(1990—),主管医师,硕士,研究方向:营养与食品安全

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刘长青,E-mail:
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Distinguishable influence of the delivery mode, feeding pattern, and infant sex on dynamic alterations in the intestinal microbiota in the first year of life[J]. Microbial Ecology, 2023, 86(3): 1799-1813., articleTitle=null, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1321170542292480110, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, xref=1, ext=[AuthorCompanyExt(id=1321170542300868719, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, companyId=1321170542292480110, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Institute of Nutrition and Food Safety, Hebei Provincial Center for Disease Control and Prevention, Shijiazhuang 050021, China), AuthorCompanyExt(id=1321170542313451632, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, companyId=1321170542292480110, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1河北省疾病预防控制中心营养与食品安全所,石家庄 050021)]), AuthorCompany(id=1321170542384754801, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, xref=2, ext=[AuthorCompanyExt(id=1321170542397337714, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, companyId=1321170542384754801, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China), AuthorCompanyExt(id=1321170542414114931, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, companyId=1321170542384754801, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2中国疾病预防控制中心营养与健康所,北京 100050)])], figs=[ArticleFig(id=1321170546532921500, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, language=EN, label=Fig.1, caption=UniFrac distance-based principal coordinate analysis plots of gut microbiota in male (left) and female (right) infants born to GDM (blue marker) and control (red marker) mothers, figureFileSmall=soq5pXp3iUyZP+eWseP/Ng==, figureFileBig=Aw1RifYpXneFOr5qLr2RbA==, tableContent=null), ArticleFig(id=1321170546600030365, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, language=CN, label=图1, caption=男婴(左)和女婴(右)的两组子代肠道菌群主坐标成分分析(PCoA), figureFileSmall=soq5pXp3iUyZP+eWseP/Ng==, figureFileBig=Aw1RifYpXneFOr5qLr2RbA==, tableContent=null), ArticleFig(id=1321170546792968350, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, language=EN, label=Fig.2, caption=Linear discriminant analysis scores of relatively abundant gut microbiota in male (left) and female (right) infants born to GDM (green) and control (red) mothers, figureFileSmall=NKWpZ4uUcnXm3qPmY3LE2w==, figureFileBig=OOfRqBY7gYRcqocnHmwTHg==, tableContent=null), ArticleFig(id=1321170546860077215, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, language=CN, label=图2, caption=男婴(左)和女婴(右)的组间子代肠道菌群LDA分值分布图

注:绿色条形代表GDM组中丰度相对较高的菌群;红色条形代表对照组中丰度相对较高的菌群。

, figureFileSmall=NKWpZ4uUcnXm3qPmY3LE2w==, figureFileBig=OOfRqBY7gYRcqocnHmwTHg==, tableContent=null), ArticleFig(id=1321170546943963296, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, language=EN, label=Fig.3, caption=Individual histograms of relatively abundant gut microbiota at the phylum level of male infants (left, 17 and 10 born to control and GDM mothers) and female infants (right, 15 and 6 born to control and GDM mothers), figureFileSmall=mHmxkvX3FjzEaX0io5n9eg==, figureFileBig=9mQ47M4hUJz73Hhw3mp1xQ==, tableContent=null), ArticleFig(id=1321170547006877857, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, language=CN, label=图3, caption=男婴(左)和女婴(右)的门水平上菌落结构柱状图, figureFileSmall=mHmxkvX3FjzEaX0io5n9eg==, figureFileBig=9mQ47M4hUJz73Hhw3mp1xQ==, tableContent=null), ArticleFig(id=1321170547086569634, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, language=EN, label=Tab.1, caption=

Differences ($ \bar{x}\pm s $) by gender in alpha diversity indices (observed species/Chao/Shannon/Simpon) of the gut microbiota between infants (10 boys and 6 girls) born to mothers with GDM and those (17 boys and 15 girls) born to control mothers

, figureFileSmall=null, figureFileBig=null, tableContent=
α多样性指数男婴女婴
合计GDM组对照组t值P值合计GDM组对照组t值P值
Observed Species指数155.74±23.54155.30±21.21156.00±25.44–0.070.94148.62±19.05136.17±19.48153.60±17.02–2.040.06
Chao1指数199.83±32.50208.99±29.70194.44±33.711.130.27178.07±21.27158.10±21.54186.05±15.53–3.34<0.01
Shannon指数2.64±0.552.60±0.522.66±0.59–0.270.792.79±0.642.48±0.572.91±0.64–1.430.17
Simpson指数0.68±0.120.66±0.130.69±0.12–0.760.460.71±0.130.67±0.120.73±0.13–1.060.29
), ArticleFig(id=1321170547162067107, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, language=CN, label=表1, caption=

不同性别、组别婴儿肠道菌群α多样性指数的比较($ \bar{x}\pm s $)

, figureFileSmall=null, figureFileBig=null, tableContent=
α多样性指数男婴女婴
合计GDM组对照组t值P值合计GDM组对照组t值P值
Observed Species指数155.74±23.54155.30±21.21156.00±25.44–0.070.94148.62±19.05136.17±19.48153.60±17.02–2.040.06
Chao1指数199.83±32.50208.99±29.70194.44±33.711.130.27178.07±21.27158.10±21.54186.05±15.53–3.34<0.01
Shannon指数2.64±0.552.60±0.522.66±0.59–0.270.792.79±0.642.48±0.572.91±0.64–1.430.17
Simpson指数0.68±0.120.66±0.130.69±0.12–0.760.460.71±0.130.67±0.120.73±0.13–1.060.29
), ArticleFig(id=1321170547237564580, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, language=EN, label=Tab.2, caption=

Genus-specific median (percentiles 25, 75) of relative abundance of six gut microbiota for male infants (all, 10 and 17 born to GDM and control mothers) and female infants (all, 6 and 15 born to GDM and control mothers)

, figureFileSmall=null, figureFileBig=null, tableContent=
菌属男婴女婴
合计GDM组对照组Z值P值合计GDM组对照组Z值P值
双歧杆菌属(Bifidobacter)40.55(17.37,61.49)50.08(15.23,64.77)40.11(23.51,60.62)<0.011.0047.41(25.78,56.90)53.49(47.41,72.64)45.71(17.19,56.90)1.360.24
罗氏菌属(Rothia)0.20(0.06,0.77)0.20(0.05,0.34)0.20(0.08,0.77)0.350.580.27(0.09,0.84)0.07(0.02,0.27)0.32(0.17,1.34)–4.420.04
乳杆菌属(Lactobacillus)1.11(0.17,3.32)2.96(1.33,13.78)0.34(0.15,1.12)4.660.030.27(0.19,1.96)0.11(0.07,0.20)1.05(0.27,4.05)–10.19<0.01
丹毒杆菌属(Erysipelatoclostridium)0.04(0.01,0.05)0.01(0.00,0.03)0.04(0.02,0.06)–4.450.040.03(0.01,0.05)0.02(0.01,0.03)0.03(0.01,0.06)–0.490.48
韦荣氏球菌属(Veillonella)0.32(0.18,1.95)0.32(0.18,3.84)0.32(0.23,1.09)<0.010.960.56(0.08,3.27)0.09(0.03,0.18)0.67(0.09,4.50)–3.490.06
肠球菌属(Enterococcus)0.44(0.13,0.70)0.25(0.09,0.46)0.57(0.34,0.70)–1.980.160.19(0.10,0.52)1.66(0.16,5.48)0.14(0.09,0.25)3.490.06
), ArticleFig(id=1321170547308867749, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321170537762631774, language=CN, label=表2, caption=

婴儿部分肠道菌群在属水平上的相对丰度[M(P25,P75)/%]

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菌属男婴女婴
合计GDM组对照组Z值P值合计GDM组对照组Z值P值
双歧杆菌属(Bifidobacter)40.55(17.37,61.49)50.08(15.23,64.77)40.11(23.51,60.62)<0.011.0047.41(25.78,56.90)53.49(47.41,72.64)45.71(17.19,56.90)1.360.24
罗氏菌属(Rothia)0.20(0.06,0.77)0.20(0.05,0.34)0.20(0.08,0.77)0.350.580.27(0.09,0.84)0.07(0.02,0.27)0.32(0.17,1.34)–4.420.04
乳杆菌属(Lactobacillus)1.11(0.17,3.32)2.96(1.33,13.78)0.34(0.15,1.12)4.660.030.27(0.19,1.96)0.11(0.07,0.20)1.05(0.27,4.05)–10.19<0.01
丹毒杆菌属(Erysipelatoclostridium)0.04(0.01,0.05)0.01(0.00,0.03)0.04(0.02,0.06)–4.450.040.03(0.01,0.05)0.02(0.01,0.03)0.03(0.01,0.06)–0.490.48
韦荣氏球菌属(Veillonella)0.32(0.18,1.95)0.32(0.18,3.84)0.32(0.23,1.09)<0.010.960.56(0.08,3.27)0.09(0.03,0.18)0.67(0.09,4.50)–3.490.06
肠球菌属(Enterococcus)0.44(0.13,0.70)0.25(0.09,0.46)0.57(0.34,0.70)–1.980.160.19(0.10,0.52)1.66(0.16,5.48)0.14(0.09,0.25)3.490.06
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妊娠期糖尿病对不同性别子代婴儿肠道菌群的影响
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张翠 1 , 赵永丽 1 , 段一凡 2 , 周园园 1 , 牛蓓 1 , 刘长青 1, *, *
中国公共卫生 | 调查报告与分析 2025,41(2): 212-216
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中国公共卫生 |调查报告与分析 2025 , 41 (2) : 212 -216
妊娠期糖尿病对不同性别子代婴儿肠道菌群的影响
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张翠1, 赵永丽1, 段一凡2, 周园园1, 牛蓓1, 刘长青1, *, *
作者信息
  • 1河北省疾病预防控制中心营养与食品安全所,石家庄 050021
  • 2中国疾病预防控制中心营养与健康所,北京 100050
通讯作者:
刘长青,E-mail:
作者简介:

张翠(1990—),主管医师,硕士,研究方向:营养与食品安全

Effect of gestational diabetes mellitus on the gut microbiota of male and female infants at 12 weeks: a hospital-based follow-up study
Cui ZHANG1, Yongli ZHAO1, Yifan DUAN2, Yuanyuan ZHOU1, Bei NIU1, Changqing LIU1
Affiliations
  • 1Institute of Nutrition and Food Safety, Hebei Provincial Center for Disease Control and Prevention, Shijiazhuang 050021, China
  • 2National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
  • Corresponding Author:
    LIU Changqing, E-mail:
出版时间: 2025-02-10 doi: 10.11847/zgggws1145737
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目的

探讨母亲妊娠期糖尿病(GDM)对不同性别子代婴儿肠道菌群的影响。

方法

于2016年6月—2019年12月,将在河北省某县医院产检的孕妇为研究对象,共913名,收集孕检和实验室检查结果相关信息,并随访其子代至12周龄,采集子代婴儿的新鲜粪便作为样本。根据孕妇2次(孕12周和孕24周)的空腹血糖检测结果进行分组,将母亲孕期2次空腹血糖结果均≥5.1 mmol/L的婴儿纳入到GDM组;将母亲孕期2次空腹血糖结果均正常的婴儿纳入到对照组。应用高通量测序技术进行16S rDNA测序检测分析。

结果

共有48名婴儿纳入到本研究,其中GDM组16人,对照组32人。女婴中GDM组的肠道菌群Chao1指数低于对照组(t=–3.34,P<0.01)。LEfSe分析显示男婴中GDM组高表达的肠道菌群为乳杆菌科/属(Lactobacillaceae、Lactobacillus),女婴中GDM组高表达的为肉杆菌科(Carnobacteriaceae)。男婴中,GDM组乳杆菌属(Lactobacillus)的相对丰度高于对照组(Z=4.66,P=0.03),丹毒杆菌属(Erysipelatoclostridium)的相对丰度低于对照组(Z= –4.45,P=0.04);女婴中,GDM组乳杆菌属(Lactobacillus)和罗氏菌属(Rothia)的相对丰度低于对照组(Z= –10.19,P<0.01;Z= –4.42,P=0.04)。门水平、属水平肠道菌群在不同性别间的差异无统计学意义(均P>0.05)。

结论

与母亲妊娠期健康的子代相比,母亲GDM子代女婴肠道菌群的丰富度降低,还可能影响子代女婴乳杆菌属(Lactobacillus)、罗氏菌属(Rothia)的相对丰度。另外女婴肠道菌群的丰富要低于男婴,但性别对婴儿肠道菌群构成影响不明显。

婴儿  /  妊娠期糖尿病  /  肠道菌群  /  性别差异  /  高通量测序技术
Objective

To study the effects of gestational diabetes mellitus (GDM) on the gut microbiota of male and female infants.

Methods

From June 2016 to December 2019, 913 singleton pregnant women (aged 18–45 years) attending prenatal examinations at a county hospital in Hebei province were enrolled in the study. Information on prenatal examinations and laboratory test results were collected, and their offspring were followed up to 12 weeks of age. Fresh fecal samples were collected from the infants as samples. Based on the results of two maternal fasting blood glucose tests (at 12 and 24 weeks of gestation), a total of 48 healthy full-term infants with no history of antibiotic use were divided into two groups: the GDM group, in which the mothers had fasting blood glucose levels ≥ 5.1 mmol/L on both tests, and the control group, in which the mothers had normal fasting blood glucose levels on both tests. 16S rDNA sequencing was performed using high-throughput sequencing technology.

Results

Of the 16 infants in the GDM group, 10 were male and 6 were female, while of the 32 infants in the control group, 17 were male and 15 were female. In the female infants, the Chao1 index of gut microbiota was lower in the GDM group than in the control group (t= –3.34, P< 0.01). LEfSe analysis showed that the highly expressed gut microbiota in the male infants of the GDM group were Lactobacillaceae and Lactobacillus, while in the female infants, it was Carnobacteriaceae. In male infants, the relative abundance of Lactobacillus was higher in the GDM group than in the control group (Z=4.66, P =0.03), and the relative abundance of Erysipelatoclostridium was lower in the GDM group than in the control group (Z= –4.45, P= 0.04). In female infants, the relative abundances of Lactobacillus and Rothia were lower in the GDM group than in the control group (Z= –10.19, P <0.01; Z= –4.42, P=0.04). There were no statistically significant gender differences in the gut microbiota at the phylum and genus level (all P > 0.05).

Conclusions

Compared with the offspring of mothers with healthy pregnancies, the gut microbiota richness of female infants of mothers with GDM was reduced, which may also affect the relative abundance of Lactobacillus and Rothia in female infants. In addition, the gut microbiota richness of female infants was lower than that of male infants, but gender had no significant effect on the composition of the infant gut microbiota.

infant  /  gestational diabetes mellitus  /  gut microbiota  /  gender difference  /  high-throughput sequencing
张翠, 赵永丽, 段一凡, 周园园, 牛蓓, 刘长青. 妊娠期糖尿病对不同性别子代婴儿肠道菌群的影响. 中国公共卫生, 2025 , 41 (2) : 212 -216 . DOI: 10.11847/zgggws1145737
Cui ZHANG, Yongli ZHAO, Yifan DUAN, Yuanyuan ZHOU, Bei NIU, Changqing LIU. Effect of gestational diabetes mellitus on the gut microbiota of male and female infants at 12 weeks: a hospital-based follow-up study[J]. Chinese Journal of Public Health, 2025 , 41 (2) : 212 -216 . DOI: 10.11847/zgggws1145737
新生儿出生后从母亲和环境中获取微生物,在这一过程中,虽然新生儿肠道菌群的丰度和多样性变化较快,但对新生儿甚至是成年以后的健康都起着重要作用,一旦受到干扰可能会导致儿童肥胖、食物过敏、早期哮喘、糖尿病等疾病的发生风险[1–5]。现今孕妇妊娠期糖尿病(gestational diabetes mellitus,GDM)的患病率呈上升趋势,已成为全球性的严重的公共卫生问题[6],且研究已证实GDM影响自身及其子代的肠道菌群分布[7]。另一方面,Yuan X等[8]的研究认为肠道菌群存在性别差异,但婴儿性别差异的相关研究较少。因此本研究以2016年6月—2019年12月在河北省某县医院产检的孕妇为研究对象,收集其孕检和实验室检查结果相关信息,并随访其子代至12周龄,最终共有48名3月龄婴儿纳入到本研究。采集子代婴儿的新鲜粪便为样本,分析母亲妊娠期糖尿病对不同性别子代婴儿肠道菌群的影响,以期为后续婴儿肠道菌群构建的研究提供参考依据。
研究中的孕妇及婴儿均来源于《中国母婴营养与健康队列研究》。于2016年6月—2019年12月,收集在河北省某县医院产检的孕妇纳入到研究,共913名,收集产检及相关信息,并随访其子代至12周龄,采集婴儿的新鲜粪便样本。分组要求如下:根据孕妇2次(孕12周和孕24周)的空腹血糖检测结果进行分组,将母亲孕期2次空腹血糖结果均≥5.1 mmol/L的婴儿纳入到GDM组;将母亲孕期2次空腹血糖结果均正常的婴儿纳入到对照组。纳入标准:(1)孕妇年龄为18~45岁且孕周<16周;(2)单胎;(3)婴儿健康足月。排除标准:(1)孕妇既往有糖尿病史、高血压史;(2)多胎;(3)孕期产检、产后及实验室资料不完整;(4)婴儿出生后使用过抗生素。根据纳入排除标准,并将未取得婴儿粪便样本的及孕妇2次血糖结果不符合分组要求的排除,最终共有48名婴儿纳入到本研究。本研究已在中国临床试验注册中心登记(登记号为:ChiCTR-OOC-16008858),并通过中国疾病预防控制中心营养与健康所伦理委员会审查(No.2016–014),所有孕妇均签署知情同意书。
所有婴儿均在出生后12周时,使用内含DNA保存液的无菌采样管留取粪便标本,采集过程遵循无菌操作,样本在采集后置于–20 ℃冰箱保存,一周内在低温的条件下(干冰)运送至实验室,置于–80 ℃冰箱保存备用。样本采集、运输、贮存过程均遵循严格统一的标准。使用QIAamp PowerFecal DNA Kit(50)试剂盒(德国凯杰,Qiagen GmbH)提取粪便样本的DNA,操作方法依照说明书。检测合格的样本基于16s rDNA基因的V3-V4可变区引物进行2次聚合酶链反应(PCR),上游引物序列为5'-ACTCCTACGGGAGGCAGCA-3',下游引物序列为5'-GGACTACHVGGGTWTCTAAT-3'。再进行文库制备、文库质检、定量,测序则采用Illumina Hiseq 2500高通量测序平台(美国,Illumina)进行。
根据97%的序列相似性水平,利用QIIME软件包中的Uclust方法进行操作性分类单元(operational taxonomic units,OTU)聚类分析。然后基于Silva(Release128 (https://www.arb-silva.de/documentation/release-128/))参考数据库,对每个样品的OTUs进行物种分类学(taxonomy)注释。粪便样本的检测和测序由中国科学院微生物研究所基因组研究中心完成。
由中国疾病预防控制中心营养与健康所和河北省疾病预防控制中心营养与食品安全所组成项目组共同完成,确保项目各阶段工作均严格依据项目工作手册进行。项目组定期对调查人员进行方法和技术培训,考核合格后方可参与调查和实验室工作。数据收集采用统一的问卷及APP,实验室采样工作至少2人专职负责,严格按照工作手册要求进行采集、运输及贮存工作。同时项目组会定期审核数据、督导检查及参与现场调查,发现问题时及时与调查员沟通并解决。
采用R4.2.1进行数据分析。计量资料采用Shapiro-Wilk法进行正态性检验,满足正态分布的以($ \bar{x}\pm s $)进行描述,组间的比较采用独立样本t检验,不满足正态分布的以[M(P25,P75)]进行描述,组间的比较采用Wilcoxon检验。以P<0.05为差异有统计学意义。
本次研究共纳入48名婴儿,其中男婴27人:GDM组10人,对照组17人;女婴21人:GDM组6人,对照组15人。男婴共333个OTU,其中GDM组314个,对照组329个,2组共享OTU数量310个,女婴共271个OTU,GDM组242个,对照组264个,2组共享OTU数量235个。本研究各样本的覆盖度均达到99%以上。
在α多样性指数中用observed species指数和Chao1指数反映菌群的丰富度,其值越高表明菌落的丰富度越高。女婴中,GDM组中菌群Chao1指数低于对照组,差异有统计学意义(t= –3.34,P<0.01)。采用Shannon指数、Simpson指数反映菌群多样性,不同性别的Shannon指数、Simpson指数在不同组间的差异均无统计学意义(均P>0.05)。在不同性别的α多样性指数分析中,女婴的菌群Chao1指数低于男婴,且差异有统计学意义(t=2.66,P=0.01)。
本研究使用(weighted)UniFrac距离的主坐标分析(pricipal coordinates analysis,PCoA),分析不同组别中肠道菌群构成的差异。男婴的第1主坐标和第2坐标对总体菌群的代表性分别为46.75%、20.16%;女婴的第1主坐标和第2坐标对总体菌群的代表性为43.14%、27.49%。经多元方差分析结果显示,不同性别的菌群结构在2组间差异均无统计学意义(P>0.05)。
采用LEfSe(linear discriminant analysis effect size)分析检测不同组间差异显著的菌群,以线性判别分析(linear discriminant analysis,LDA)估计每个差异丰富的分类单元的影响大小(LDA效应阈值设定为2)。男婴中GDM组高表达的肠道菌群为乳杆菌科/属(Lactobacillaceae、Lactobacillus),对照组高表达的为丹毒杆菌属(Erysipelatoclostridium);女婴中GDM组高表达的为肉杆菌科(Carnobacteriaceae),对照组中高表达的为微球菌目/科(Micrococcales、Micrococcaceae)、罗氏菌属(Rothia)、乳杆菌科/属(Lactobacillaceae、Lactobacillus)。
图3反映了不同组别婴儿肠道菌群门水平上的组成情况。男婴检出7个门,依次为放线菌门(Actinobacteria)、厚壁菌门(Firmicutes)、变形菌门(Proteobacteria)、拟杆菌门(Bacteroidetes)、疣微菌门(Verrucomicrobia)、梭杆菌门(Fusobacteria)和螺旋体门(Saccharibacteria)。女婴检出6个门,与男婴相比未检出梭杆菌门(Fusobacteria)。各菌门水平上的相对丰度在组间的差异均无统计学意义(均P>0.05)。
男婴中,GDM组优势菌属根据相对丰度占比由高到低依次为:双歧杆菌属(Bifidobacter)、乳杆菌属(Lactobacillus)、Ambiguous_taxa、克雷伯氏菌属(Klebsiella)、韦荣氏球菌属(Veillonella)、链球菌属(Streptococcus)。对照组依次为双歧杆菌属(Bifidobacter)、链球菌属(Streptococcus)、埃希氏菌属(Escherichia)、类杆菌属(Bacteroides),其中GDM组乳杆菌属(Lactobacillus)的相对丰度高于对照组(Z=4.66,P=0.03),丹毒杆菌属(Erysipelatoclostridium)的相对丰度低于对照组(Z=–4.45,P=0.04)。女婴中,GDM组优势菌属根据相对丰度占比由高到低依次为:双歧杆菌属(Bifidobacter)、埃希氏菌属(Escherichia)、Ambiguous_taxa、类杆菌属(Bacteroides)、链球菌属(Streptococcus);对照组为双歧杆菌属(Bifidobacter)、链球菌属(Streptococcus)、埃希氏菌属(Escherichia)、类杆菌属(Bacteroides)、韦荣氏球菌属(Veillonella)。其中GDM组乳杆菌属(Lactobacillus)和罗氏菌属(Rothia)的相对丰度均低于对照组(Z=–10.19,P<0.01;Z=–4.42,P=0.04)。在不同性别的菌属分析中,属水平的肠道菌群在不同性别间的差异无统计学意义(均P>0.05)。
生命早期肠道菌群的建立,是人类成长与发展的关键窗口期,在健康和疾病的多个方面发挥着重要作用。本研究对3月龄婴儿肠道菌群进行研究,探讨了母亲妊娠期糖尿病对不同性别子代婴儿肠道菌群的影响。在肠道菌群多样性方面,多项研究认为GDM组肠道菌群丰富度(Chao1指数)降低[9–10],如Su M L等[10]对新生儿的研究发现,GDM组的Chao1指数显著低于对照组,而Shannon指数、Simpson指数在组间差异无统计学意义,与本次对女婴α多样性的研究结果相类似,提示GDM组子代女婴肠道菌群的丰富度可能会降低。
在菌群结构门水平上,婴儿肠道菌群在不同组别中均主要由放线菌门(Actinobacteria)、厚壁菌门(Firmicutes)、变形菌门(Proteobacteria)、拟杆菌门(Bacteroidetes)构成,且为放线菌门(Actinobacteria)的双歧杆菌属(Bifidobacter)占主导地位,这与在儿童生命早期的肠道菌群特点相类似[11]。属水平上,在男婴中GMD组的乳杆菌属(Lactobacillus)的相对丰度增加,LEfSe分析也显示该组高表达乳杆菌科/属(Lactobacillaceae、Lactobacillus),分析可能与该组男婴儿均为母乳喂养有关,母乳喂养婴儿的肠道菌群中乳杆菌属(Lactobacillus)的丰度较高[12]。在女婴中发现GDM组乳杆菌属(Lactobacillus)、罗氏菌属(Rothia)的相对丰度降低,有研究也表明GDM影响子代的乳杆菌属(Lactobacillus)[9–10 ,13]、罗氏菌属(Rothia)[14]等部分属水平的肠道菌群。另外LEfSe分析显示女婴GDM组高表达的有肉杆菌科(Carnobacteriaceae),对照组高表达的微球菌科(Micrococcaceae)、罗氏菌属(Rothia),这与Crusell M K W等[14]的研究结果相似。
目前,关于性别对婴儿期肠道菌群的研究较少,其中有研究认为与环境、抗生素等因素相比,性别对婴儿肠道菌群的影响较小[15–16],但Ma X等[17]的研究显示性别是决定1~6月龄婴儿肠道菌群定植的主要因素之一。本研究显示女婴肠道菌群的丰富度要低于男婴,门水平和属水平肠道菌群在不同性别间的差异均无统计学意义。分析未得出统一结论的原因,可能与婴儿时期肠道菌群不稳定有关,不同的研究设计也可能会导致结果的不同。
综上所述,与母亲妊娠期健康的子代相比,母亲GDM子代女婴肠道菌群的丰富度降低,还可能影响子代女婴乳杆菌属(Lactobacillus)、罗氏菌属(Rothia)的相对丰度,另外女婴肠道菌群的丰富度要低于男婴,但性别对婴儿肠道菌群构成影响不明显。然而鉴于肠道菌群易受环境因素、喂养方式、分娩方式等多种因素影响,所以母亲GDM对不同性别子代婴儿肠道菌群的分布所产生的影响,尚需通过更完善的研究设计进行深入研究。

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2025年第41卷第2期
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doi: 10.11847/zgggws1145737
  • 接收时间:2024-08-30
  • 首发时间:2026-10-25
  • 出版时间:2025-02-10
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  • 收稿日期:2024-08-30
  • 修回日期:2024-09-12
  • 录用日期:2024-11-08
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    1河北省疾病预防控制中心营养与食品安全所,石家庄 050021
    2中国疾病预防控制中心营养与健康所,北京 100050

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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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