Since the early 20th century, it is well known that the fetus is free of germs in utero and that microbial colonization begins during the delivery by contamination with the mother’s microbiotas (vaginal, perineal and fecal microbiotas). More than a century later, the hypothesis that the placenta barrier keeps fetuses sterile throughout a healthy pregnancy still remains a general dogma and, as a consequence, the presence of any bacteria in the uterus is generally considered as a potential danger for the fetus.

However, new data can modify these evidences ! Investigations into the potential for bacterial transmission through the placental barrier have detected bacteria in placenta tissue, umbilical cord blood, amniotic fluid, and fetal membranes from healthy newborns without any indication of infection or inflammation (1). Furthermore, the analysis of meconium (first intestinal excretion of the newborn) shows a complex microbial community.

A recent study characterized the microbiota of meconium and fecal samples obtained from preterm babies during the first 3 weeks of life (2). It has been shown that spontaneously released meconium of such neonates contains a specific microbiota that differs from those observed in early fecal samples (Firmicutes mainly detected in meconium while Proteobacteria was abundant in feces). An analysis of the genetic material revealed the high prevalence of bacteria related to Streptococcus mitis and Lactobacillus plantarum in meconium, whereas those related to E. coli, Enterococcus, and K. pneumoniae predominated in the infant feces. Another study conducted in 23 newborns highlights the microbial richness of meconium, which was not affected by the mode of delivery (3).

But how can bacteria reach the fetus ? The mechanism is not well understood, however it has been suggested that bacteria travel to the placenta via the bloodstream after gut epithelium translocation (1). While the intestinal epithelial barrier generally prevents microbial entry into the circulatory system, dendritic cells could actively penetrate the gut epithelium, take up bacteria from the intestinal lumen, and transport the live bacteria throughout the body as they migrate to lymphoid organs. Two pioneer studies (4,5) investigated if oral administration of a genetically labeled Enterococcus faecium to pregnant mice resulted in its presence in amniotic fluid and meconium of term offspring after sterile cesarean section. Remarkably, E. faecium with the genetic label was cultured from the amniotic fluid and meconium of pups from inoculated mothers, but not from pups of control mice.

The first hypothesis of the sterile fetus is called into question by these recent findings that emphasize the importance of gut microbiota on the in utero environment during pregnancy, childbirth, the baby’s development but also on the future health status of the neonate throughout his life.

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References

(1) RODRIGUEZ JM, MURPHY K STANTON C, ROSS RP, KOBER OI, JUGE N, AVERSHINA E, RUDI K, NARBAD A, JENMALM MC, MARCHESI JR, COLLADO MC. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015, 26:26050

(2) MOLES L, GOMEZ M, HEILIG H, BUSTOS G, FUENTES S, DE VOS W, FERNANDEZ L, RODRIGUEZ JM, JIMENEZ E. Bacterial diversity in meconium of preterm neonates and evolution of their fecal microbiota during the first month of life. PLoS One. 2013; 8(6):e66986

(3) HU J, NOMURA Y, BASHIR A, FERNANDEZ-HERNANDEZ H, ITZKOWITZ S, PEI Z, STONE J, LOUDON H, PETER I. Diversified microbiota of meconium is affected by maternal diabetes status. PLoS One. 2013 Nov 6;8(11):e78257

(4) JIMENEZ E, FERNANDEZ L, MARIN ML, MARTIN R, ODRIOZOLA JM, NUENO-PALOP C, NARBAD A, OLIVARES M, XAUS J, RODRIGUEZ JM. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Curr Microbiol. 2005, 51(4):270-4

(5) JIMENEZ E, MARIN ML, MARTIN R, ODRIOZOLA JM, OLIVARES M, XAUS J, FERNANDEZ L, RODRIGUEZ JM. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008, 159(3):187-93