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Microbiome. 2017 Apr 28;5(1):48. doi: 10.1186/s40168-017-0268-4.

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

Author information

1
Department of Agriculture, Food and Nutritional Sciences, 4-126 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada.
2
Department of Physiology and Pharmacology, University of Calgary, Cumming School of Medicine, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada.
3
Department of Pediatrics, University of Calgary, Cumming School of Medicine, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada.
4
Department of Food Science and Technology, 260 Food Innovation Center, University of Nebraska-Lincoln, 1901 N 21st Street, Lincoln, Nebraska, 68588-6205, USA.
5
Department of Agriculture, Food and Nutritional Sciences, 4-126 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada. jwalter1@ualberta.ca.
6
Department of Biological Sciences, 7-142 Katz Group Centre, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada. jwalter1@ualberta.ca.

Abstract

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.

KEYWORDS:

Axenic animals; Contamination; In utero colonization; Microbiome; Placenta; Sterile womb

PMID:
28454555
PMCID:
PMC5410102
DOI:
10.1186/s40168-017-0268-4
[Indexed for MEDLINE]
Free PMC Article

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