收稿日期: 2023-06-09
录用日期: 2023-12-05
网络出版日期: 2024-01-28
基金资助
国家重点研发计划重点专项(2017YFE0124700);国家自然科学基金(81961128023);上海交通大学医学院“双百人”项目(20152518)
Relationship among maternal gut, vaginal microbiota and microbiota in meconium and vernix caseosa in newborns
Received date: 2023-06-09
Accepted date: 2023-12-05
Online published: 2024-01-28
Supported by
National Key R&D Program of China(2017YFE0124700);National Natural Science Foundation of China(81961128023);“Two-hundred Talents” Program of Shanghai Jiao Tong University School of Medicine(20152518)
目的·分析母亲孕晚期肠道菌群、阴道菌群、新生儿胎粪及胎皮脂菌群的多样性及菌群构成,比较其异同及相关性。方法·前瞻性研究。招募2018年8月—11月于上海交通大学医学院附属新华医院分娩的11对母婴,采集母亲孕晚期粪便样本、阴道拭子及新生儿胎粪;招募2018年12月于上海交通大学医学院附属国际和平妇幼保健院分娩的14名新生儿,采集额部、腋窝、腹股沟部位的胎皮脂及胎粪样本。所有孕妇均为阴道自然分娩。采用16S rRNA基因V3~V4区测序进行微生物检测,分析11对母婴中母亲的肠道菌群、阴道菌群和新生儿的胎粪菌群,以及14名新生儿的胎皮脂菌群和胎粪菌群的多样性、菌群构成,分析异同及相关性。结果·母亲肠道菌群的操作分类单元(operational taxonomic unit,OTU)数、Ace指数、Chao1指数、Shannon指数均高于阴道菌群和新生儿胎粪菌群;新生儿3个部位胎皮脂菌群的Ace指数和Chao1指数均显著高于胎粪菌群(均P<0.01)。母亲肠道菌群、阴道菌群和新生儿胎粪菌群β多样性存在差异(P<0.01);新生儿额部、腋窝和腹股沟3个部位胎皮脂菌群的β多样性相似,但与胎粪菌群存在差异(P<0.01)。在门水平上,母亲肠道菌群优势菌主要为厚壁菌门(Firmicutes,52.76%)和拟杆菌门(Bacteroidetes,41.67%),阴道菌群优势菌为厚壁菌门(74.36%)和放线菌门(Actinobacteria,21.25%),胎皮脂菌群的优势菌为厚壁菌门(84.22%)和变形菌门(Proteobacteria,8.80%),新生儿胎粪菌群在2个批次样本中优势菌均为变形菌门(分别占81.11%和88.72%)。在属水平上,母亲肠道菌群的优势菌为拟杆菌属(Bacteroides,35.42%)和栖粪杆菌属(Faecalibacterium,10.12%),阴道菌群的优势菌为乳杆菌属(Lactobacillus,69.10%)和双歧杆菌属(Bifidobacterium,11.30%),胎皮脂菌群的优势菌为乳杆菌属(79.81%)和假单胞菌属(Pseudomonas,3.23%),胎粪菌群的优势菌在2个批次样本中均为埃希菌属(Escherichia,分别占55.21%和31.18%)。结论·母亲孕晚期肠道菌群的α多样性高于阴道菌群和新生儿胎粪菌群,新生儿胎皮脂菌群α多样性高于胎粪菌群。厚壁菌门在母亲孕晚期肠道菌群、阴道菌群及新生儿胎皮脂菌群中均为优势菌,乳杆菌属在母亲阴道菌群及新生儿胎皮脂菌群中均为优势菌,胎粪菌群以变形菌门和埃希菌属较多。新生儿不同身体部位的胎皮脂菌群结构相似,但与胎粪菌群存在差异。
马锦倩 , 范翩翩 , 郑涛 , 张琳 , 陈远志 , 申剑 , 欧阳凤秀 . 孕妇肠道、阴道菌群和新生儿胎粪、胎皮脂菌群的相关性研究[J]. 上海交通大学学报(医学版), 2024 , 44(1) : 50 -63 . DOI: 10.3969/j.issn.1674-8115.2024.01.006
Objective ·To analyze the diversity and composition of the maternal gut microbiota and vaginal microbiota in late pregnancy, neonatal meconium microbiota and vernix caseosa microbiota, and analyze the similarities, differences and correlations. Methods ·This is a prospective study. Maternal stool samples and vaginal swabs in late-pregnancy, and neonatal meconium samples were collected from 11 mother-infant pairs at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August to November 2018; the vernix caseosa from three sites (forehead, axilla, and inguinal crease) and meconium samples were collected from 14 healthy newborns at International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine in December 2018. All births were vaginal deliveries. The 16S rRNA gene V3?V4 region sequencing was used. The diversity, composition and similarities/differences of the maternal gut microbiota, the vaginal microbiota, and the neonatal meconium microbiota from the 11 mother-infant pairs, as well as the neonatal vernix caseosa microbiota and the meconium microbiota from the 14 newborns were analyzed. Results ·The number of operational taxonomic units (OTUs), ACE index, Chao1 index, and Shannon index of maternal gut microbiota were all higher than those of vaginal microbiota; the ACE indices and the Chao1 indices of the vernix caseosa microbiota at three sites were all higher than those of meconium microbiota (P<0.01). The β diversity varied among the maternal gut microbiota, vaginal microbiota, and neonatal meconium microbiota (P<0.01). The β diversity of neonatal vernix caseosa microbiota from three sites (forehead, axilla, and inguinal crease) was similar, but different from meconium microbiota (P<0.01). At the phylum level, the dominant bacteria were Firmicutes (52.76%) and Bacteroidetes (41.67%) in the maternal gut microbiota, Firmicutes (74.36%) and Actinobacteria (21.25%) in the maternal vaginal microbiota, and Firmicutes (84.22%) and Proteobacteria (8.80%) in the neonatal vernix caseosa microbiota. The dominant bacterium in the neonatal meconium was Proteobacteria in the two batches of samples (81.11% and 88.72%, respectively). At the genus level, the dominant bacteria were Bacteroides (35.42%) and Faecalibacterium (10.12%) in the maternal gut microbiota, Lactobacillus (69.10%) and Bifidobacterium (11.30%) in the vaginal microbiota, and Lactobacillus (79.81%) and Pseudomonas (3.23%) in the vernix caseosa microbiota. The dominant bacterium in the neonatal meconium was Escherichia in the two batches of samples (55.21% and 31.18%, respectively). Conclusion ·The α diversity of maternal gut microbiota is higher than that of vaginal microbiota and neonatal meconium microbiota, and it is higher in neonatal vernix caseosa than that in meconium microbiota. The Firmicutes is the predominant phylum in the maternal late-pregnancy gut microbiota, vaginal microbiota, and neonatal vernix microbiota. Lactobacillus is the predominant genus in both maternal vaginal and neonatal vernix caseosa microbiota. Proteobacteria in phylum and Escherichia in genus are predominant in meconium microbiota. The microbiota composition is similar in vernix caseosa at different body sites, but there are differences between the vernix caseosa microbiota and meconium microbiota.
1 | LI D T, WANG P, WANG P P, et al. The gut microbiota: a treasure for human health[J]. Biotechnol Adv, 2016, 34(7): 1210-1224. |
2 | WAMPACH L, HEINTZ-BUSCHART A, FRITZ J V, et al. Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential[J]. Nat Commun, 2018, 9(1): 5091. |
3 | ARRIETA M C, ARéVALO A, STIEMSMA L, et al. Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting[J]. J Allergy Clin Immunol, 2018, 142(2): 424-434.e10. |
4 | RAUTAVA S, LUOTO R, SALMINEN S, et al. Microbial contact during pregnancy, intestinal colonization and human disease[J]. Nat Rev Gastroenterol Hepatol, 2012, 9(10): 565-576. |
5 | KRONMAN M P, ZAOUTIS T E, HAYNES K, et al. Antibiotic exposure and IBD development among children: a population-based cohort study[J]. Pediatrics, 2012, 130(4): e794-e803. |
6 | STOUT M J, CONLON B, LANDEAU M, et al. Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations[J]. Am J Obstet Gynecol, 2013, 208(3): 226.e1-226.e7. |
7 | MOREIRA L B, SILVA C B D, GERALDO-MARTINS V R, et al. Presence of Streptococcus mutans and interleukin-6 and -10 in amniotic fluid[J]. J Matern Fetal Neonatal Med, 2022, 35(25): 9463-9469. |
8 | WITT R G, BLAIR L, FRASCOLI M, et al. Detection of microbial cell-free DNA in maternal and umbilical cord plasma in patients with chorioamnionitis using next generation sequencing[J]. PLoS One, 2020, 15(4): e0231239. |
9 | MAKINO H, KUSHIRO A, ISHIKAWA E, et al. Mother-to-infant transmission of intestinal bifidobacterial strains has an impact on the early development of vaginally delivered infant's microbiota[J]. PLoS One, 2013, 8(11): e78331. |
10 | ARBOLEYA S, SáNCHEZ B, MILANI C, et al. Intestinal microbiota development in preterm neonates and effect of perinatal antibiotics[J]. J Pediatr, 2015, 166(3): 538-544. |
11 | FALLANI M, YOUNG D, SCOTT J, et al. Intestinal microbiota of 6-week-old infants across Europe: geographic influence beyond delivery mode, breast-feeding, and antibiotics[J]. J Pediatr Gastroenterol Nutr, 2010, 51(1): 77-84. |
12 | VISSCHER M O, NARENDRAN V, PICKENS W L, et al. Vernix caseosa in neonatal adaptation[J]. J Perinatol, 2005, 25(7): 440-446. |
13 | ECHARRI P P, GRACIá C M, BERRUEZO G R, et al. Assessment of intestinal microbiota of full-term breast-fed infants from two different geographical locations[J]. Early Hum Dev, 2011, 87(7): 511-513. |
14 | TAPIAINEN T, PAALANNE N, TEJESVI M V, et al. Maternal influence on the fetal microbiome in a population-based study of the first-pass meconium[J]. Pediatr Res, 2018, 84(3): 371-379. |
15 | STINSON L F, BOYCE M C, PAYNE M S, et al. The not-so-sterile womb: evidence that the human fetus is exposed to bacteria prior to birth[J]. Front Microbiol, 2019, 10: 1124. |
16 | KLOPP J, FERRETTI P, MEYER C U, et al. Meconium microbiome of very preterm infants across Germany[J]. mSphere, 2022, 7(1): e0080821. |
17 | TANG N, LUO Z C, ZHANG L, et al. The association between gestational diabetes and microbiota in placenta and cord blood[J]. Front Endocrinol, 2020, 11: 550319. |
18 | MITCHELL C M, HAICK A, NKWOPARA E, et al. Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women[J]. Am J Obstet Gynecol, 2015, 212(5): 611.e1-611.e9. |
19 | THEIS K R, ROMERO R, WINTERS A D, et al. Does the human placenta delivered at term have a microbiota? Results of cultivation, quantitative real-time PCR, 16S rRNA gene sequencing, and metagenomics[J]. Am J Obstet Gynecol, 2019, 220(3): 267.e1-267.e39. |
20 | STERPU I, FRANSSON E, HUGERTH L W, et al. No evidence for a placental microbiome in human pregnancies at term[J]. Am J Obstet Gynecol, 2021, 224(3): 296.e1-296.e23. |
21 | FERRETTI P, PASOLLI E, TETT A, et al. Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome[J]. Cell Host Microbe, 2018, 24(1): 133-145.e5. |
22 | ROBERTSON R C, MANGES A R, FINLAY B B, et al. The human microbiome and child growth: first 1000 days and beyond[J]. Trends Microbiol, 2019, 27(2): 131-147. |
23 | WAMPACH L, HEINTZ-BUSCHART A, HOGAN A, et al. Colonization and succession within the human gut microbiome by Archaea, bacteria, and microeukaryotes during the first year of life[J]. Front Microbiol, 2017, 8: 738. |
24 | MILLER J L, SONIES B C, MACEDONIA C. Emergence of oropharyngeal, laryngeal and swallowing activity in the developing fetal upper aerodigestive tract: an ultrasound evaluation[J]. Early Hum Dev, 2003, 71(1): 61-87. |
25 | MILANI C, DURANTI S, BOTTACINI F, et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota[J]. Microbiol Mol Biol Rev, 2017, 81(4): e00036-e00017. |
26 | JIMéNEZ E, FERNáNDEZ L, MARíN M L, et al. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section[J]. Curr Microbiol, 2005, 51(4): 270-274. |
27 | LIU C J, LIANG X, NIU Z Y, et al. Is the delivery mode a critical factor for the microbial communities in the meconium?[J]. EBioMedicine, 2019, 49: 354-363. |
28 | GOMEZ DE AGüERO M, GANAL-VONARBURG S C, FUHRER T, et al. The maternal microbiota drives early postnatal innate immune development[J]. Science, 2016, 351(6279): 1296-1302. |
29 | FER?EK I, LUGOVI?-MIHI? L, TAMBI?-ANDRA?EVI? A, et al. Features of the skin microbiota in common inflammatory skin diseases[J]. Life, 2021, 11(9): 962. |
30 | TA?EB A. Skin barrier in the neonate[J]. Pediatr Dermatol, 2018, 35(Suppl 1): s5-s9. |
31 | NISHIJIMA K, YONEDA M, HIRAI T, et al. Biology of the vernix caseosa: a review[J]. J Obstet Gynaecol Res, 2019, 45(11): 2145-2149. |
32 | MESFIN S, AFEWORK M, BIKILA D, et al. Distribution of vernix caseosa and associated factors among newborns delivered at Adama Comprehensive Specialized Hospital Medical College, Ethiopia, in 2022: cross-sectional study[J]. Clin Cosmet Investig Dermatol, 2022, 15: 2903-2914. |
33 | GRICE E A, KONG H H, CONLAN S, et al. Topographical and temporal diversity of the human skin microbiome[J]. Science, 2009, 324(5931): 1190-1192. |
34 | KONG H H. Skin microbiome: genomics-based insights into the diversity and role of skin microbes[J]. Trends Mol Med, 2011, 17(6): 320-328. |
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