Care and observation of a germ-free neonate.

Barnes, R. D.; Bentovim, Arnon; Hensman, S.; Piesowicz, A T

doi:10.1136/adc.44.234.211

Cited by 9 publications

(7 citation statements)

References 16 publications

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“…Infection may be detectable in a minority of placenta samples from pre-term birth, though here too possible contamination of placenta specimens with vaginal lineages provides an alternative explanation for most cases. Our data is congruent with the observation that axenic (germ free) mammals can be generated routinely [ 19 , 20 ]—in numerous studies, mammalian neonates have been delivered by sterile cesarean section into sterile isolators, after which they remain sterile. It is hard to sustain the idea that the womb is normally colonized by microbes given this observation.…”

Section: Discussionsupporting

confidence: 89%

“…This method is used routinely to derive germ-free mouse strains and has been used to derive germ-free rats, guinea pigs, rabbits, dogs, cats, pigs, lambs, calves, goats, baboons, chimpanzees, and marmosets [ 19 ]. Even germ-free humans have been generated by this method [ 19 , 20 ]. This observation provides strong evidence against the idea that contents of the gravid uterus (placenta, amniotic cavity, and fetus) are colonized with microbes.…”

Section: Introductionmentioning

confidence: 99%

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Lack of detection of a human placenta microbiome in samples from preterm and term deliveries

et al. 2018

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BackgroundHistorically, the human womb has been thought to be sterile in healthy pregnancies, but this idea has been challenged by recent studies using DNA sequence-based methods, which have suggested that the womb is colonized with bacteria. For example, analysis of DNA from placenta samples yielded small proportions of microbial sequences which were proposed to represent normal bacterial colonization. However, an analysis by our group showed no distinction between background negative controls and placenta samples. Also supporting the idea that the womb is sterile is the observation that germ-free mammals can be generated by sterile delivery of neonates into a sterile isolator, after which neonates remain germ-free, which would seem to provide strong data in support of sterility of the womb.ResultsTo probe this further and to investigate possible placental colonization associated with spontaneous preterm birth, we carried out another study comparing microbiota in placenta samples from 20 term and 20 spontaneous preterm deliveries. Both 16S rRNA marker gene sequencing and shotgun metagenomic sequencing were used to characterize placenta and control samples. We first quantified absolute amounts of bacterial 16S rRNA gene sequences using 16S rRNA gene quantitative PCR (qPCR). As in our previous study, levels were found to be low in the placenta samples and indistinguishable from negative controls. Analysis by DNA sequencing did not yield a placenta microbiome distinct from negative controls, either using marker gene sequencing as in our previous work, or with shotgun metagenomic sequencing. Several types of artifacts, including erroneous read classifications and barcode misattribution, needed to be identified and removed from the data to clarify this point.ConclusionsOur findings do not support the existence of a consistent placental microbiome, in either placenta from term deliveries or spontaneous preterm births.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0575-4) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Lack of detection of a human placenta microbiome in samples from preterm and term deliveries

et al. 2018

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“…The first germ-free human was delivered by performing a C-section inside a sterile canopy attached to the mother’s abdomen, which prevented exposure to environmental contaminants [126]. Gram stains of feces and aerobic and anaerobic cultures of swabs from both the infant and the isolator surfaces confirmed the germ-free status of the infant [126, 129, 130]. The published cases report axenic status from 6 days to 3 months after which the subjects were either removed from the axenic isolators or microbial contamination was detected [126, 127, 129, 131].…”

Section: Pondering the Two Hypothesesmentioning

confidence: 99%

A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome

et al. 2017

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After more than a century of active research, the notion that the human fetal environment is sterile and that the neonate’s microbiome is acquired during and after birth was an accepted dogma. However, recent studies using molecular techniques suggest bacterial communities in the placenta, amniotic fluid, and meconium from healthy pregnancies. These findings have led many scientists to challenge the “sterile womb paradigm” and propose that microbiome acquisition instead begins in utero, an idea that would fundamentally change our understanding of gut microbiota acquisition and its role in human development. In this review, we provide a critical assessment of the evidence supporting these two opposing hypotheses, specifically as it relates to (i) anatomical, immunological, and physiological characteristics of the placenta and fetus; (ii) the research methods currently used to study microbial populations in the intrauterine environment; (iii) the fecal microbiome during the first days of life; and (iv) the generation of axenic animals and humans. Based on this analysis, we argue that the evidence in support of the “in utero colonization hypothesis” is extremely weak as it is founded almost entirely on studies that (i) used molecular approaches with an insufficient detection limit to study “low-biomass” microbial populations, (ii) lacked appropriate controls for contamination, and (iii) failed to provide evidence of bacterial viability. Most importantly, the ability to reliably derive axenic animals via cesarean sections strongly supports sterility of the fetal environment in mammals. We conclude that current scientific evidence does not support the existence of microbiomes within the healthy fetal milieu, which has implications for the development of clinical practices that prevent microbiome perturbations after birth and the establishment of future research priorities.

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“…There they remained sterile. 14,15 What would allow the idea of the colonized womb to be preserved, given what seem to be conclusive data for sterility from gnotobiotic studies? It is hard to propose a workable model, even allowing ad hoc wild speculation.…”

mentioning

confidence: 99%

De-Discovery of the Placenta Microbiome

Bushman

2019

American Journal of Obstetrics and Gynecology

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Care and observation of a germ-free neonate.

Cited by 9 publications

References 16 publications

Lack of detection of a human placenta microbiome in samples from preterm and term deliveries

Lack of detection of a human placenta microbiome in samples from preterm and term deliveries

A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome

De-Discovery of the Placenta Microbiome

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