Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer.
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ABSTRACT:
SUBMITTER: Dominguez-Bello MG
PROVIDER: S-EPMC5062956 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
Publications
Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer.
Dominguez-Bello Maria G MG De Jesus-Laboy Kassandra M KM Shen Nan N Cox Laura M LM Amir Amnon A Gonzalez Antonio A Bokulich Nicholas A NA Song Se Jin SJ Hoashi Marina M Rivera-Vinas Juana I JI Mendez Keimari K Knight Rob R Clemente Jose C JC
Nature medicine 20160201 3
Exposure of newborns to the maternal vaginal microbiota is interrupted with cesarean birthing. Babies delivered by cesarean section (C-section) acquire a microbiota that differs from that of vaginally delivered infants, and C-section delivery has been associated with increased risk for immune and metabolic disorders. Here we conducted a pilot study in which infants delivered by C-section were exposed to maternal vaginal fluids at birth. Similarly to vaginally delivered babies, the gut, oral and ...[more]
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Project description:BackgroundEarly microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth.MethodsUsing 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth.FindingsCompositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study.ConclusionsThe results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth.FundingC&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.
| S-EPMC9123283 | biostudies-literature
Project description:Importance:Pneumococcal nasopharyngeal carriage is a prerequisite for pneumococcal disease. The main transmission route is from toddlers, who commonly carry pneumococci. However, neonatal pneumococcal disease case reports suggest that vertical pneumococcal transmission may also occur. Objective:To describe and compare pneumococcal nasopharyngeal carriage and density by infant mode of delivery in young Fijian infants. Design, Setting, and Participants:Annual cross-sectional surveys were performed in Suva, Fiji, before the introduction of 10-valent pneumococcal conjugate vaccine (PCV10), from September 14 to December 20, 2012, and after PCV10 was introduced, from July 11 to November 19, 2013; July 15 to December 9, 2014; and August 13 to November 19, 2015. Caregivers of 2006 infants aged 5 to 8 weeks participated in the surveys. Statistical analysis was performed from May 24, 2018, to August 12, 2019. Exposures:Caregivers provided data on infant mode of delivery and demographics via interviewer-led survey. Main Outcomes and Measures:Pneumococci in swab samples were detected and quantified by lytA quantitative polymerase chain reaction with molecular serotyping by microarray. Pneumococci were categorized as PCV10 or non-PCV10 serotypes. Results:Of the 2006 infants (976 girls and 1030 boys; mean [SD] age, 6.1 [0.02] weeks]), 1742 (86.8%) were born vaginally and 264 were born by cesarean delivery. Infants delivered vaginally, compared with those born by cesarean delivery, had a higher prevalence of overall pneumococcal nasopharyngeal carriage (470 of 1722 [27.3%; 95% CI, 25.2%-29.4%] vs 47 of 260 [18.1%; 95% CI, 13.6%-23.3%]; P?=?.002), PCV10 carriage (113 of 1698 [6.7%; 95% CI, 5.5%-7.9%] vs 8 of 256 [3.1%; 95% CI, 1.4%-6.1%]; P?=?.03), and non-PCV10 carriage (355 of 1698 [20.9%; 95% CI, 19.0%-22.9%] vs 38 of 256 [14.8%; 95% CI, 10.7%-19.8%]; P?=?.02), and had higher median densities of overall pneumococci (4.9 log10 genome equivalents [GE]/mL [interquartile range, 4.8-5.0 log10 GE/mL] vs 4.5 log10 GE/mL [interquartile range, 4.1-4.6 log10 GE/mL]; P?=?.01) and non-PCV10 pneumococci (4.9 log10 GE/mL [interquartile range, 4.7-5.0 log10 GE/mL] vs 4.4 log10 GE/mL [interquartile range, 4.0-4.7 log10 GE/mL]; P?=?.01). Vaginal delivery was associated with overall (adjusted odds ratio, 1.57 [95% CI, 1.10-2.23]; P?=?.01) and non-PCV10 (adjusted odds ratio, 1.49 [95% CI, 1.01-2.20]; P?=?.04]) pneumococcal nasopharyngeal carriage. Vaginal delivery was not associated with PCV10 carriage (adjusted odds ratio, 1.67 [95% CI, 0.80-3.51]; P?=?.17). After adjustment, vaginal delivery was not associated with density. Conclusions and Relevance:Pneumococcal nasopharyngeal carriage prevalence and density were higher in infants delivered vaginally compared with those delivered by cesarean birth. After adjustment, vaginal delivery was associated with pneumococcal carriage. Differences in carriage by mode of delivery may be due to differential exposure to the vaginal microbiota during delivery and the effect of intrapartum antibiotics during cesarean delivery on the infant microbiome. Our findings also raise the hypothesis that vertical transmission may contribute to pneumococcal acquisition.
| S-EPMC6813584 | biostudies-literature
Project description:The rate of cesarean delivery (CD) in China has risen sharply and the high rate was reported to be associated with increased risk of disease in the offspring. However, there is little research on the molecular mechanism of critical pathways and gene signatures involved in the neonatal immunity of cesarean-born infants. This study was undertaken to identify unique gene signatures which was involved in the neonatal immunity of cesarean-born infants through large-scale RNA-sequencing. Genes differentially expressed in cesarean-born infants were identified and further validated through quantitative real-time PCR (RT-qPCR). Moreover, we employed weighted gene co-expression network analysis (WGCNA) to identify highly connected genes that were correlated with neonatal inflammation. In total, 73 differentially expressed genes (DEGs) were identified between cesarean-born infants and normal vagina childbirth. The results obtained by secondary validation indicated that GATM, MIF, IFI27, IL1B, CA1, and EPHB1 were significantly upregulated in phenotype CD, while CYP2A6 and DLK1 were significantly down regulated. Further, functional and pathway enrichment analysis reveals perturbation of several DEGs involved in signaling pathways pertaining to immunoregulation, inflammation, apoptosis, and nervous development. Additionally, HLA-DOB popped out as a core gene in the process of inflammation, which might indicate the risk of cesarean-born infants for inflammatory disease. Notably, our study for the first time has documented gene signatures PIK3CA, PTPRC, SOS1, IL6ST, and MALT1, which were found to be involved in neonatal inflammation. Taken together, the full expression repertoire including the differentially expressed gene sets and core differentially co-expressed genes should provide an excellent resource for identifying potential biomarkers of cesarean-born infants with inflammation, and formulating new hypotheses for physiological functions and the discovery of novel therapeutic targets for inflammatory disease.
2019-01-23 | GSE125421 | GEO
Project description:Helicobacter pylori colonization may affect the mucosal immune system through modification of microbiota composition and their interactions with the host. We hypothesized that maternal H. pylori status affects the maternal intestinal microbiota of both mother and newborn. In this study, we determine the structure of the fecal microbiota in mothers and neonates according to maternal H. pylori status and delivery mode. We included 22 mothers and H. pylori infection was determined by fecal antigen test. Eleven mothers (50%) were H. pylori-positive (7 delivering vaginally and 4 by C-section), and 11 were negative (6 delivering vaginally and 5 by C-section). Stool samples were obtained from mothers and infants and the fecal DNA was sequenced. The fecal microbiota from mothers and their babies differed by the maternal H. pylori status, only in vaginal birth, not in C-section delivery. All 22 infants tested negative for fecal H. pylori at 15 days of age, but those born vaginally -and not those by C-section- showed differences in the infant microbiota by maternal H. pylori status (PERMANOVA, p?=?0.01), with higher abundance of Enterobacteriaceae and Veillonella, in those born to H. pylori-positive mothers. In conclusion, the structure of the infant fecal microbiota is affected by the maternal H. pylori status only in infants born vaginally, suggesting that the effect could be mediated by labor and birth exposures.
| S-EPMC7190710 | biostudies-literature
Project description:For decades, babies were thought to be born germ-free, but recent evidences suggest that they are already exposed to various bacteria in utero. However, the data on population levels of such pioneer gut bacteria, particularly in context to birth mode, is sparse. We herein aimed to quantify such bacteria from the meconium of 151 healthy term Japanese infants born vaginally or by C-section. Neonatal first meconium was obtained within 24-48 h of delivery; RNA was extracted and subjected to reverse-transcription-quantitative PCR using specific primers for Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Atopobium cluster, Prevotella, Bifidobacterium, Lactobacillus, Enterococcus, Enterobacteriaceae, Staphylococcus, Enterococcus, Streptococcus, C. perfringens, and C. difficile. We detected several bacterial groups in both vaginally- and cesarean-born infants. B. fragilis group, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus were detected in more than 50% of infants, with counts ranging from 105 to 108 cells/g sample. About 30-35% samples harbored Bifidobacterium and Lactobacillus (104-105 cells/g); whereas C. coccoides group, C. leptum subgroup and C. perfringens were detected in 10-20% infants (103-105 cells/g). Compared to vaginally-born babies, cesarean-born babies were significantly less often colonized with Lactobacillus genus (6% vs. 37%; P = 0.01) and Lactobacillus gasseri subgroup (6% vs. 31%; P = 0.04). Overall, seven Lactobacillus subgroups/species, i.e., L. gasseri subgroup, L. ruminis subgroup, L. casei subgroup, L. reuteri subgroup, L. sakei subgroup, L. plantarum subgroup, and L. brevis were detected in the samples from vaginally-born group, whereas only two members, i.e., L. gasseri subgroup and L. brevis were detected in the cesarean group. These data corroborate that several bacterial clades may already be present before birth in term infants' gut. Further, lower detection rate of lactobacilli in cesarean-born babies suggests that the primary source of lactobacilli in infant gut is mainly from maternal vaginal and-to a lesser extent-anal microbiota during vaginal delivery, and that the colonization by some important Lactobacillus species is delayed in babies delivered via cesarean-section.
| S-EPMC5156933 | biostudies-literature
Project description:Maternal FMT in Cesarean-Born Infants - WGS sequencing of infants (1w to 1year) and maternal fecal samples
| PRJEB64567 | ENA
Project description:BackgroundExclusive breastfeeding promotes beneficial modifications on the microbiota of cesarean born infants, but little is known about the role of specific breast milk components in this modulation. Women with an active FUT2 gene (called secretors) secrete α1-2 fucosylated human milk oligosaccharides (HMOs), which promote Bifidobacterium in the infant's gut and may modulate the microbiota of cesarean born infants.ObjectiveTo compare the microbiota composition of cesarean and vaginally born infants breastfed by secretor mothers.MethodsMaternal secretor status was determined by the occurrence of 4 different α1-2 fucosylated HMOs in breast milk by LC-MS. The fecal microbiota composition from cesarean and vaginally born infants was analyzed by 16S rRNA gene sequencing and qPCR, stratified by the maternal secretor status, and compared.ResultsAlpha and beta diversity were not significantly different in cesarean born, secretor-fed infants (CSe+) compared to vaginally born, secretor-fed infants (VSe+). There were no significant differences in the fecal relative abundance of Bifidobacterium between CSe+ and VSe+ infants, but the prevalence of the species B. longum was lower in CSe+. The fecal relative abundance of Bacteroides was also lower, while Akkermansia and Kluyvera were higher in CSe+ infants.ConclusionCesarean and vaginally born infants fed with breast milk containing the α1-2 fucosylated HMOs fraction present similar amounts of Bifidobacterium in the feces, but differences are observed in other members of the microbiota.
| S-EPMC7870049 | biostudies-literature
Project description:The maternal vaginal microbiome is an important source for infant gut microbiome development. However, infants delivered by Cesarean section (CS) do not contact the maternal vaginal microbiome and this delivery method may perturb the early establishment and development of the gut microbiome. The aim of this study was to investigate the early gut microbiota of Korean newborns receiving the same postpartum care services for two weeks after birth by delivery mode using fecal samples collected at days 3, 7, and 14. Early gut microbiota development patterns were examined using 16S rRNA gene-based sequencing from 132 infants either born vaginally (VD, n = 64) or via Cesarean section (CS, n = 68). VD-born neonates showed increased alpha diversity in infant fecal samples collated at days 7 and 14 compared to those from day 3, while those of CS infants did not differ (p < 0.015). Bacterial structures of infants from both groups separated at day 7 (p < 0.001) and day 14 (p < 0.01). The bacterial structure of VD infants gradually changed over time (day 3 vs. day 7, p < 0.012; day 3 vs. day 14, p < 0.001). Day 14 samples of CS infants differed from day 3 and 7 samples (day 3 vs. day 14, p < 0.001). VD infant relative abundance of Bifidobacterium (days 7, 14), Bacteroides (days 7, 14), and Lachnospiraceae (day 7) significantly increased compared to CS infants, with a lower abundance of Enterobacteriaceae (found in all periods of the CS group) (LDA > 3.0). Relative abundances of Bifidobacterium, Lactobacillus, and Staphylococcus were significantly increased in both VD and CS groups at day 14 (LDA > 3.0). Predicted functional analysis showed that VD infants had overrepresented starch/sucrose, amino acid and nucleotide metabolism in gut microbiota with depleted lipopolysaccharide biosynthesis until day 14 compared to CS infants. This study confirmed that delivery mode is the major determinant of neonatal intestinal microbiome establishment and provides a profile of microbiota perturbations in CS infants. Our findings provide preliminary insight for establishing recovery methods to supply the specific microbes missing in CS infants.
| S-EPMC7516058 | biostudies-literature
Project description:Children delivered by elective, prelabor Cesarean section (C-section) are not exposed to the birth canal microbiota and, in relation to vaginally delivered children, show altered microbiota development. Perturbed microbial colonization during critical early-life windows of development alters metabolic and immune programming and is associated with an increased risk of immune and metabolic diseases. In nonrandomized studies, vaginal seeding of C-section-born neonates partially restores their microbiota colonization to that of their vaginally delivered counterparts, but without randomization, confounding factors cannot be excluded. In a double-blind, randomized, placebo-controlled trial, we determined the effect of vaginal seeding versus placebo seeding (control arm) on the skin and stool microbiota of elective, prelabor C-section-born neonates (n = 20) at 1 day and 1 month after birth. We also examined whether there were between-arm differences in engraftment of maternal microbes in the neonatal microbiota. In relation to the control arm, vaginal seeding increased mother-to-neonate microbiota transmission and caused compositional changes and a reduction in alpha diversity (Shannon Index) of the skin and stool microbiota. The neonatal skin and stool microbiota alpha diversity when maternal vaginal microbiota is provided is intriguing and highlights the need of larger randomized studies to determine the ecological mechanisms and effects of vaginal seeding on clinical outcomes. IMPORTANCE Children delivered by elective C-section are not exposed to the birth canal and show altered microbiota development. Impairing microbial colonization during early life alters metabolic and immune programming and is associated with an increased risk of immune and metabolic diseases. In a double-blind, randomized, placebo-controlled trial, we determined the effect of vaginal seeding on the skin and stool microbiota of elective C-section born neonates and found that vaginal seeding increased mother-to-neonate microbiota transmission and caused compositional changes and a reduction in the skin and stool microbiota diversity. The reduction of neonatal skin and stool microbiota diversity when maternal vaginal microbiota is provided is intriguing and highlights the need of larger randomized studies to determine the ecological mechanisms and effects of vaginal seeding on clinical outcomes.
| S-EPMC10294643 | biostudies-literature
Project description:BackgroundNeonatal health at delivery as measured by apgar scores is an important outcome. This study was done to assess the impact of anesthesia on Apgar 1-minute and 5-minute scores of infants delivered through elective cesarean section in Zimbabwe.MethodsWe carried out a secondary analysis of data from the Efficacy of Tranexamic Acid in Preventing Postpartum Hemorrhage (ETAPPH) clinical trial in Zimbabwe. Outcomes measured were infant Apgar scores at 1 and 5 min, exposure was the administration of either a general (intravenous propofol/ketamine/sodium thiopental) or spinal (hyperbaric bupivacaine 0.5%) anesthesia for anesthesia during the elective cesarean section procedure. Marginal Structural Logistic Modelling (MSM) using an unstabilized Inverse Probability Treatment Weight (IPTW) estimator was used to assess the relationship between anesthetic administration method and infant Apgar scores.ResultsFour hundred and twenty-one (421) women who had an elective caesarean section in the ETAPPH study had their infants assessed for Apgar scores. Comparing general anesthesia to spinal anesthesia, spinal anesthesia was related to good Apgar scores at 1-minute (adjusted odds ratio [aOR] = 4.0, 95% Confidence Interval = 1.5-10.7, sensitivity analysis E-value = 3.41). Spinal anesthetic administration was also related to good Apgar scores at 5 min (adjusted odds ratio [aOR] = 6.2, 95% Confidence Interval = 1.6-23.1, sensitivity analysis E-value = 4.42).ConclusionsWhen providing anesthesia for patients undergoing elective cesarean section, care should be taken on the method of administration of anesthetic agents. General anesthesia tends to depress Apgar scores at 1 min, although most neonates recover and have better scores at 5 min. Spinal anesthesia should be the first choice whenever possible.Trial registrationThe clinical trial from which data of this study was abstracted was registered under clinical trials registration number NCT04733157.
| S-EPMC10134612 | biostudies-literature