The prenatal gut microbiome: are we colonized with bacteria in utero?

Abstract

The colonization of the gut with microbes in early life is critical to the developing newborn immune system, metabolic function and potentially future health. Maternal microbes are transmitted to offspring during childbirth, representing a key step in the colonization of the infant gut. Studies of infant meconium suggest that bacteria are present in the foetal gut prior to birth, meaning that colonization could occur prenatally. Animal studies have shown that prenatal transmission of microbes to the foetus is possible, and physiological changes observed in pregnant mothers indicate that in utero transfer is likely in humans as well. However, direct evidence of in utero transfer of bacteria in humans is lacking. Understanding the timing and mechanisms involved in the first colonization of the human gut is critical to a comprehensive understanding of the early life gut microbiome. This review will discuss the evidence supporting in utero transmission of microbes from mother to infants. We also review sources of transferred bacteria, physiological mechanisms of transfer and modifiers of maternal microbiomes and their potential role in early life infant health. Well-designed longitudinal birth studies that account for established modifiers of the gut microbiome are challenging, but will be necessary to confirm in utero transfer and further our knowledge of the prenatal microbiome.

Keywords: Bacteria; foetal development; gut microbiome; pregnancy.

Conflict of interest statement

Conflict of Interest Statement

The authors declare no conflicts of interest.

© 2017 World Obesity Federation.

Figures

Figure 1. Maternal sites that may contribute to offspring gut microbiome

During pregnancy there are changes to maternal microbiomes. Translocation of bacteria from the oral and gut microbiomes of mothers during pregnancy, in addition to ascension of bacteria from the vaginal microbiome, may explain the presence of non-pathogenic bacteria in intrauterine locations. Maternal-derived bacteria detected in neonatal meconium, a proxy for the in utero gut microbiome, is suggestive of the prenatal transfer of bacteria from mother to infant.

Figure 2. Proposed mechanisms of maternal transfer of bacteria to the fetus in utero

Gut: The lumen of the maternal distal gut is lined with enterocytes that under normal conditions form a cellular and mucosal barrier to gut microbes (yellow spheres). Diet, stress, antibiotic exposure, disease and pregnancy may alter the thickness of the mucosal layer and the integrity of the enterocyte border. Gaps in this layer (intestinal permeability) allow bacteria to cross the intestinal barrier into blood or lymphatic vessels where they translocate to other body sites. Similarly, resident dendritic cells (DC) probe the lumen and transport bacteria across the gut border in an immune stimulating process. Oral: Dental injury or surgery and oral conditions that cause inflammation (gingivitis) allow oral bacteria contained in salivary and subgingival microbiome communities exposure to the circulatory system. Placenta: Bacteria already present in the endometrial lining or urogenital regions may be incorporated into the developing placental decidua. Bacteria transferred in the blood from other maternal microbiomes to the placenta may populate the decidua, fetal membranes and sinuses and transfer to the developing fetus in utero via amniotic fluid and cord blood.