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

By M. Perez-Muñoz, M. Arrieta, A. Ramer-Tait, J. Walter. Microbiome, 2017

908 citations recorded by the source corpus.

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.

Subfields: Geochemistry and Petrology, Pharmaceutical Science, Radiation

View Paper: https://www.semanticscholar.org/paper/5b346ffd70c48a7e9d69761a8b69acdbdcca5de5

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Citations in the corpus

The Human Microbiome and Child Growth - First 1000 Days and Beyond. (2019, background): “The Fetal Microbiota Microbial invasion of the amniotic cavity is associated with preterm birth and other adverse birth outcomes; however, the hypothesis of fetal exposure to a more complex placental microbiota in healthy pregnancies remains under debate [15,23,24].”
The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota (2017, background): “Finally, gnotobiology has been claimed as the strongest evidence against the existence of microbiomes in the fetal environment because of the ability to derive germfree animals via C-sections and subsequently raise the offspring in a sterile environment (66).”
Mother-to-Infant Microbial Transmission from Different Body Sites Shapes the Developing Infant Gut Microbiome (2018, background): “offering evidence of the occurrence of intra-uterine seeding (Aagaard et al., 2014; Perez-Munoz et al., 2017; Rodriguez et al., 2015), but the role and importance of prenatal microbial colonization are still open to debate (Jimenez et al.”