Furthermore, specific bacteria present in amniotic fluid and placenta were also detected in the meconium samples by DGGE Fig. B A neighbour joining phylogenetic tree representing the sequences obtained from maternal faeces samples, placenta, amniotic fluid, colostrum, meconium and infant faeces samples.
Maternal faeces pink , placenta yellow , amniotic fluid red , colostrum light blue , meconium dark blue and infant faeces green samples are shown as single points. D Heatmap plot of Hierarchical Ward-linkage clustering based on the similarity measure Euclidean distance of phylum proportion. Sequences were normalized by log transformation. Individual maternal faeces pink , placenta yellow , amniotic fluid red , colostrum light blue , meconium dark blue and infant faeces green samples are shown as single points.
Despite these similarities between amniotic fluid, placenta and meconium microbiota, the overall microbial composition and activity in meconium appears unique. Significant differences were observed between the activity of the amniotic fluid and meconium microbiota Fig. In addition, the LDA Effect Size LEfSe: Linear Discriminant Analysis Effect Size algorithm used to identify taxa with differing abundance in amniotic fluid and meconium samples revealed that while Enterobacteriaceae are the predominant bacteria in the placenta, meconium samples differ from the placenta particularly with regard to high numbers of Bacillaceae and Streptococcaceae Fig.
On the phylum level, the meconium microbiota is dominated by Firmicutes Figs 1A and 3D and Staphylococcaceae was the most frequent bacterial family detected in meconium samples Fig. These findings are consistent with a previous report on microbial composition of meconium in preterm infants A Bacterial taxa that were differentially abundant in placenta and meconium samples visualised using a cladogram generated from LEfSe analysis. B Differences in key OTUs identified as differentiating between placenta and meconium samples.
C Bacterial taxa that were differentially abundant in placenta and colostrum samples visualized using a cladogram generated from LEfSe analysis. D Differences in key OTUs identified as differentiating between placenta and colostrum samples. The meconium microbiota exhibited a notable correlation with the colostrum microbiota in some individuals Figs 1C,D and 3B,C. Of the 75 bacterial family level phylotypes detected in the meconium samples, 54 were also detected in colostrum Fig.
In certain individuals, specific bacteria present in colostrum were also detected in meconium Fig.
It is of note that the colostrum and amniotic fluid microbiota also share features Figs 1C and 3A,B,D , Supplementary Table 3 , while significant differences were also detected in both microbiota composition Fig. Consistently with a previous report 24 , the microbial composition observed in infant faecal samples collected later in the first week of life was clearly distinct from that of meconium Fig.
Moreover, the infant faecal microbiota at 3—4 days of life displayed notable similarity with colostrum Fig. Our data demonstrate that human amniotic fluid and placenta harbour unique microbial communities, which may provide the initial inoculum for gut colonisation, the single most important determinant of host-microbe interaction modulating the risk of non-communicable disease. The distinct microbial populations in placenta, amniotic fluid and colostrum and the consistency of the findings across individuals observed in this study suggest that there may be active and selective mechanisms by which bacteria are transported to these maternal compartments.
The origin of the intrauterine microbiota is currently not known. Similarities between human oral and placenta microbial communities have previously been suggested 11 but the study relied on oral microbiota data from a previous report based on non-pregnant individuals and the mechanism of possible bacterial transport between these confined maternal compartments remains unknown. In contrast, there are mechanistic data consistent with the notion that both breast milk and intrauterine microbes may originate in the maternal gut.
We have previously reported that the composition of the intestinal microbiota changes dramatically during pregnancy in humans 25 and increased intestinal bacterial translocation has been reported in experimental animals during pregnancy and lactation Specific labelled bacteria introduced to the gut of pregnant mice have been detected in the placenta in an experimental animal model There are data indicating that maternal intestinal microbes may be actively transported to breast milk by immune cells in the systemic circulation in both lactating mice and humans Consequently, we hypothesise that maternal intestinal microbes may be selectively transported to the mammary gland and to the foeto-placental interface.
Microbes in the amniotic cavity have previously been investigated primarily as potential pathogens causing infection or premature labour, but recently the dogma of sterile foetal life has been challenged 1. Several investigators have reported the presence of microbes in meconium 13 , 14 , 15 but their origin has not been known. Recently, the bacteria in meconium have been reported to reflect maternal health 27 and also to be associated with the development of disease in the offspring Combining observations from separate studies, it has been speculated that the meconium microbiota may be derived from swallowed amniotic fluid We present here for the first time comprehensive analyses of the microbiota in the placenta, amniotic fluid and meconium from the same mother-infant pairs.
Only infants born by elective caesarean section were included in this study. While it is important to recognize that this population does not reflect the physiological continuum of microbial contact during pregnancy, vaginal delivery and breastfeeding, the study design allowed us to exclude the impact of bacterial transfer during labour and delivery. Mothers, who presented with rupture of membranes, labour, or signs of infection were excluded from the study to minimise contamination of the placenta and amniotic fluid samples.
Contamination of the meconium samples with environmental microbes cannot be ruled out since the specimens were collected noninvasively from diapers, but the procedures were designed to avoid contamination as much as possible. Based on detection of both live microbes and microbial DNA, the intrauterine compartment appears to harbour a unique microbiota with a distinct composition and activity. Shared features and specific bacteria as well as clustering of microbial findings in meconium on the one hand and placenta and amniotic fluid on the other suggest that colonisation of the foetal intestine may indeed be initiated in utero by microbes in the placenta and amniotic fluid.
This notion is consistent with data from an experimental animal model according to which specific bacteria introduced to the gut of pregnant animals may be recovered in the meconium of the offspring after sterile caesarean section The microbial composition observed in meconium also exhibits common features with the colostrum microbiota. All the infants in the study were breastfed from the first hours of life and it is therefore possible that microbes from colostrum or other postnatal environmental sources may have had an impact on the microbial composition of meconium, which was passed during the first two days of life.
Given our data suggesting that the impact of colostrum microbes on gut colonisation is more evident later in the first week of life and the fact that meconium is formed during foetal life, it is perhaps more likely that meconium and colostrum microbiota share a common maternal source than that colostrum directly contributes to the meconium microbiota. This notion is consistent with the hypothesised mechanism of maternal intestinal bacterial transport to both the mammary gland and the placenta and amniotic fluid discussed above.
Interestingly, the colostrum microbiota also appears to exhibit specific metagenomic activity. The role of breast milk microbes beyond the hypothesised contribution to neonatal gut colonisation remains unknown. None of the infants in this study received formula during the study period. Rigorous comparison of microbial transfer and gut colonisation in breastfed and formula-fed infants should be conducted and might provide more insight into the significance of breast milk bacteria. To our knowledge, this is the first study to report the direct impact of prenatal bacterial exposure on foetal gut colonisation in healthy term pregnancy by integrating microbiological data from placenta, amniotic fluid and meconium samples from the same mother-infant pairs.
Based on the present data, we hypothesise that the process of healthy immune maturation guided by intestinal microbial contact may begin already during foetal life.
You and Your Hormones
The contribution of maternal microbes to human gut colonisation continues after birth via microbes in breast milk. Bacterial transfer from the mother during the perinatal period may offer a novel target for devising interventions aiming to reduce inflammatory non-communicable disease risk by modulating early host-microbe interactions. This study is based on samples collected from subjects participating in a randomized, double-blind placebo-controlled clinical trial clinicaltrials. Pregnant women scheduled to undergo elective caesarean section after 37 weeks of gestation were recruited to obtain placenta samples without risk of contamination taking place during vaginal delivery.
Mothers with conditions, which might affect placental and foetal physiology e. Amniotic fluid, placenta, meconium, colostrum, infant faeces and maternal faeces samples were available from 15 mother-infant pairs and included in this study. One mother received antenatal antibiotic therapy with clindamycin for a bacterial infection of the skin whilst the remaining 14 mothers received no antibiotics prior to or during the caesarean section. None of the neonates were administered antibiotics.
The detailed clinical characteristics of these mother-infant pairs are presented in Table 1. The study was approved by the Ethics committee of the Intermunicipal Hospital District of Southwest Finland and conducted in accordance with the Declaration of Helsinki as well as national legislation and institutional guidelines concerning clinical research. Informed consent was obtained from all subjects.
Meconium and infant faeces samples were collected from diapers after they had been passed. Meconium, infant faecal samples and maternal faecal samples were collected fresh in sterile plastic recipients, refrigerated and processed without further delay. Colostrum samples were collected in the maternity hospital using milk produced within 24 hours after delivery. Before sample collection, the breast was cleaned with an iodine swab to reduce contamination from skin bacteria, and breast milk was collected manually discarding the first drops with a sterile milk collection unit.
Placenta samples approximately 10 mg were kept under anaerobic conditions AnaeroGen; Oxoid, Hampshire, United Kingdom , and analysed in less than 2 hours to avoid alterations in bacterial viability. All the viable and cultivable bacteria recovered from placenta and amniotic fluid samples were isolated and re-streaked onto the same agar media. For preliminary identification of the isolates, conventional microbiological methods were used, including analysis of colony and cellular morphology and Gram staining.
Bacterial isolates were grown in the same isolation broth media and harvested at the late log growth phase. DNA from the reference strains was extracted as previously described Amplification was confirmed by gel electrophoresis in 1. The bands and band matching were manually corrected when seen necessary. The number of bands present in the DGGE profile was used as a measure of richness for the samples.
Specificity and amplicon size were verified by gel electrophoresis and the amplicons were checked and measured using the Agilent High Sensitivity DNA assay in Agilent Expert. From the resulting raw data set provided by pyrosequencing, low quality sequences were filtered out to remove sequences having a length shorter than nucleotides and chimeric sequences were removed using UCHIME software Quality filtering and final reads number data of the 16S rRNA profiling analysis are presented in Supplementary Table 5.
Phylogenetic identification of the organisms on the family and genus levels are presented as read numbers in Supplementary Table 1 and as relative abundances in Supplementary Table 2. To estimate diversity conservatively and reduce noise in patterns of beta diversity, singleton OTUs were removed prior to community analysis.
The Chao1 alpha diversity curves for the sample types as well as individual samples are provided in Supplementary Figure 1. Most of the samples reached a plateau suggesting sufficient coverage of the microbes present in the samples. Microbial Beta-diversity between samples was evaluated and computed from the previously constructed OTU table using UniFrac, a phylogenetic distance metric that measures community similarity based on the degree to which pairs of communities share branch length in a common phylogenetic tree Unweighted and weighted UniFrac distances and sample metadata comprised the data matrices used as inputs for principal coordinate analysis PCoA.
PCoA plots were used to assess the variation in the composition of microbial communities between samples and to visualise potential clustering of samples by metadata.
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Biplots were generated as part of the beta diversity analyses, using genus level OTU tables showing principle coordinate sample clustering alongside weighted taxonomic group data. All beta-diversity measures were performed on OTU tables rarefied to sequences per sample for all samples to account for variations in sequencing depth. Data on assigned sequences at family level shared between samples were used to generate a Venn diagram.
After taxonomical assignment, relative frequencies of different taxonomic categories obtained were calculated using the Statistical Analysis of Metagenomic Profiles program STAMP v. MEGAN v. Data-filtering was performed by the interquantile range method followed by quantile normalisation within replicates after log transformation.
Principal component analyses and identification of significant features were performed for all sample groups together. LEfSe couples robust tests for measuring statistical significance Kruskal-Wallis test with quantitative tests for biological consistency Wilcoxon-rank sum test. The differentially abundant and biologically relevant features are ranked by effect size after undergoing linear discriminant analysis LDA. An effect size threshold between 2—3 on a log 10 scale was used for all biomarkers discussed in this study.
In short, this software allows the prediction of functional pathways from the 16S rRNA reads. Supervised analysis was done using LEfSe to elicit the microbial functional pathways that were differentially expressed in the different samples. How to cite this article : Collado, M. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Rautava, S. Microbial contact during pregnancy, intestinal colonization and human disease. Placental expulsion can be managed actively, for example by giving oxytocin via intramuscular injection followed by cord traction to assist in delivering the placenta.
Alternatively, it can be managed expectantly, allowing the placenta to be expelled without medical assistance. Blood loss and the risk of postpartum bleeding may be reduced in women offered active management of the third stage of labour, however there may be adverse effects and more research is necessary. The habit is to cut the cord immediately after birth, but it is theorised that there is no medical reason to do this; on the contrary, it is theorized that not cutting the cord helps the baby in its adaptation to extrauterine life , especially in preterm infants.
The placenta is traditionally thought to be sterile , but recent research suggests that a resident, non-pathogenic , and diverse population of microorganisms may be present in healthy tissue. However, whether these microbes exist or are clinically important is highly controversial and is the subject of active research. The placenta intermediates the transfer of nutrients between mother and fetus. The perfusion of the intervillous spaces of the placenta with maternal blood allows the transfer of nutrients and oxygen from the mother to the fetus and the transfer of waste products and carbon dioxide back from the fetus to the maternal blood.
Placenta: How it works, what's normal - Mayo Clinic
Nutrient transfer to the fetus can occur via both active and passive transport. Waste products excreted from the fetus such as urea , uric acid , and creatinine are transferred to the maternal blood by diffusion across the placenta. IgG antibodies can pass through the human placenta, thereby providing protection to the fetus in utero. IgM , however, cannot cross the placenta, which is why some infections acquired during pregnancy can be hazardous for the fetus. Furthermore, the placenta functions as a selective maternal-fetal barrier against transmission of microbes.
However, insufficiency in this function may still cause mother-to-child transmission of infectious diseases. The placenta and fetus may be regarded as a foreign body inside the mother, and needs to be protected from the normal immune response of the mother that would cause it to be rejected.
The placenta and fetus are thus treated as sites of immune privilege , with immune tolerance. However, the Placental barrier is not the sole means to evade the immune system, as foreign fetal cells also persist in the maternal circulation, on the other side of the placental barrier. The placenta also provides a reservoir of blood for the fetus, delivering blood to it in case of hypotension and vice versa, comparable to a capacitor. The placenta often plays an important role in various cultures , with many societies conducting rituals regarding its disposal.
In the Western world , the placenta is most often incinerated. Some cultures bury the placenta for various reasons. The placenta is believed by some communities to have power over the lives of the baby or its parents. The Kwakiutl of British Columbia bury girls' placentas to give the girl skill in digging clams, and expose boys' placentas to ravens to encourage future prophetic visions. In Turkey , the proper disposal of the placenta and umbilical cord is believed to promote devoutness in the child later in life.
In Ukraine , Transylvania , and Japan , interaction with a disposed placenta is thought to influence the parents' future fertility. Several cultures believe the placenta to be or have been alive, often a relative of the baby. Nepalese think of the placenta as a friend of the baby; Malaysian Orang Asli regard it as the baby's older sibling.
In some cultures, the placenta is eaten, a practice known as placentophagy. Some cultures have alternative uses for placenta that include the manufacturing of cosmetics, pharmaceuticals and food. Picture of freshly delivered placenta and umbilical cord wrapped around Kelly clamps. Micrograph of a placental infection CMV placentitis. From Wikipedia, the free encyclopedia. Organ that connects the fetus to the uterine wall. This article is about the human placenta.
For general information about the placenta as an organ in biology, see placentation. For the ancient Roman Bread, see placenta food. Human placenta from just after birth with the umbilical cord in place. Further information: Placentation. Further information: Fetal circulation. Main article: Placental expulsion. Main article: Placental microbiome. Further information: Immune tolerance in pregnancy. Main article: Placental disease. Magnified a little over two diameters. Close-up of umbilical attachment to fetal side of freshly delivered placenta.
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Herpetology: Third Edition. Archived from the original on Online Etymology Dictionary. Most likely this is due to the beneficial effect of estrogen. Maternal weight at birth is a strong determinant of neonatal birth weight. When maternal birth weight is less than 5. This means that the babies of women born small for gestation, do not realize the nutritional advantage of their expected genetic potential and of course, this leads to bad health consequences later on.
Pregnancy is a wonderful, natural phenomenon. It transforms the female body to a life generator. For this to be achieved, the maternal body must undergo certain changes in order to support the development of the fetus from a tiny, single cell organism to a complete human being. This includes, gastrointestinal, renal and cardiovascular changes but not only.
Several studies in animals and humans have shown that periconceptional time before pregnancy as well as during pregnancy maternal nutritional state plays a very important role in the subsequent development of the fetus. Nutritional imbalances prior to conception exert a significant effect on the quality of placental development and subsequent fetal growth.
Balanced nutrition prior to conception in contrast leads to a healthy and well-grown neonate. Nutritional deprivation during pregnancy affects fetal growth differently at different stages of development. Nutritional insufficiency prior to conception and during the first trimester , limits fetal growth and the neonate will be proportionately small giving the appearance of a normal small neonate.
The newborn is likely to be skinny and long suggestive of a genetic potential that was not fulfilled due to the insufficient nutritional supplies at a critical time that the baby was determined to grow faster according to its own growth trajectory. The baby by means of metabolic alterations and developmental programming reduces its nutritional demands in order to survive and grow according to the new growth pattern.
When fetuses are deprived, they have the capacity to change the function of their genes in order to reduce their metabolic needs. This is achieved by the so-called epigenetic imprinting, a methylation de-methylation process that changes the normal functionality of a gene. By doing so, fetuses decrease their metabolic needs and thus become able to survive a a hostile environment with limited supplies.