Does a Prenatal Bacterial Microbiota Exist?
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COMMENTARY Does a prenatal bacterial microbiota exist? M Hornef1 and J Penders2 THE CONCEPT OF A PRENATAL the establishment of the neonate’s own meconium samples of 21 healthy human MICROBIOME microbiota.4 Recently, maternal-fetal neonates born by either vaginal delivery The recent technical progress and enor- transmission of commensal bacteria or caesarean section and cultured mous efforts to unravel the manifold and the existence of a placental micro- bacteria of the genera Staphylococcus, interactions of the microbiota with the biome have been suggested.5–10 Coloni- Enterococcus, Streptococcus, Leuconos- host’s organism have provided striking zation of the healthy placental and/or toc, Bifidobacterium, Rothia, Bacteroides and unforeseen insights. This work fetal tissue with a diverse group of but also of the Proteobacteria Klebsiella, assigns the microbiota a central role metabolically active bacteria would; Enterobacter and Escherichia coli.6 in human health and has identified novel however, fundamentally challenge our Again, oral administration of the labeled strategies to prevent and fight diseases in current thinking of the development of E. faecium strain to pregnant mice led to the future. One particular aspect of this the fetus within a sterile, protected the detection in meconium samples.6 work has been the early colonization of environment. It would require new They concluded the presence of the newborn and a strong influence of concepts to explain how bacteria can ‘‘mother-to-child transmission’’ before maternal sources on the developing persist within host tissue but remain birth. Three other groups described the microbiota of the neonate.1,2 Birth, or anatomically restricted to prevent sys- PCR-based detection of bacteria in more accurately rupture of the amniotic temic spread within the fetal organism placental tissue. Rautava et al. detected membranes that surround the embryo and how preterm birth, a condition bacterial DNA mainly from the genus and separate it physically from the lumen causally linked to bacterial infection of Lactobacillus as well as the mostly of the uterus first exposes the neonate to the amniotic tissue, is prevented. It obligate anaerobic growing genera Bifi- the environment and is generally con- would also raise important questions dobacterium, Bacteroides and Clostri- sidered the start of the microbiota on the origin, composition and stability dium in 29 of 29 placental samples establishment. More recently, the exis- of the placental microbiome and its after elective cesarean section.7 The tence of a placental microbiome, and influence on the developing host and group of Versalovic performed a thus maternal-fetal transmission of postnatal microbiome. metagenomic approach on placental microorganisms and microbial coloni- In support of the concept of a prenatal specimen collected under sterile condi- zation of the fetal organism before birth microbiome, Jime´nez et al. reported on tions from 320 individuals after vaginal has been suggested. This commentary the cultural detection of low numbers of delivery or cesarean section and critically discusses the available data. Enterococcus faecium, Staphylococcus described a low-abundance microbiome It is generally believed that the fetus in epidermidis and Propionibacterium including the phyla Firmicutes, Tener- utero develops in the absence of viable acnes from human cord blood samples icutes, Proteobacteria, Bacteroides and microorganisms. This is consistent with after elective cesarean section.5 This Fusobacteria.8 A recent study by Bassols the observation that cesarean section- analysis was complemented by a mouse et al., examined placental tissue of 22 born rodents can serve to generate germ- study in which they administered a vaginally delivered neonates from free animals.3 Only with rupture of genetically labeled human E. faecium mothers with or without gestational membranes and passage through the isolate orally to pregnant mice and diabetes aseptically collected and pre- birth canal, the newborn becomes reported detection of this strain from pared after childbirth in the delivery or exposed to colonized maternal body cultures of amniotic fluid.5 A subsequent operating room.9 PCR and 16S rDNA surfaces and the environment initiating study from the same group analyzed sequencing revealed the presence of 1Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany and 2Department of Medical Microbiology, NUTRIM School of Nutrition and Translational Research in Metabolism & Caphri School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, The Netherlands. Correspondence: MW Hornef ([email protected]) Published online 25 January 2017. doi:10.1038/mi.2016.141 598 VOLUME 10 NUMBER 3 | MAY 2017 | www.nature.com/mi COMMENTARY Proteobacteria, Bacteroidetes, Firmi- pipet tips and (even commercial) by PCR and culture and significant cutes, and Actinobacteria.9 Placental reagents such as spin columns or differences in the main taxa of the tissue of women with gestational diabetes enzymes representing a source for false placental microbiome were described exhibited a distinct microbiota profile positive results. This problem is well in three other reports.8–10,13 which was amongst others characterized known to medical microbiologists or Additionally, transient bacteremia, by a lower relative abundance in the forensic scientists who are frequently i.e., the presence of viable bacteria in Pseudomonadales order and Acineto- confronted with the situation to judge on blood is occasionally observed in the bacter genus and an increased the value and meaning of a positive PCR healthy host. For example, bacteria can abundance in the Lachnospiraceae, signal. Of note, this problem can almost be cultured from blood samples after Coriobacteriaceae and Bradyrizobiaceae be neglected when studying densely dental hygiene.14 Similarly, mechanical families and the genera Escherichia and populated ecological niches such as manipulation of heavily colonized geni- Parabacteroides.9 Both PCR- and cul- the enteric microbiota but becomes a tal body surfaces as it occurs during ture-based methods were used by the critical issue when studying samples with vaginal delivery or the abdominal skin group of Salminen to examine placental low bacterial density. Therefore, exten- incision during cesarean section is tissue and amniotic fluid of 15 electively sive technical precautions during sample expected to facilitate bacterial entry into cesarean section delivered human new- acquisition and processing, the imple- the maternal bloodstream.15 Although borns. 16S rDNA sequencing detected a mentation of adequate internal controls bacteria are rapidly eliminated by serum- "low-richness, low-diversity" bacterial at all steps during sample preparation derived or cellular host defense mechan- composition with a predominance of and analysis and a critical interpretation isms in the healthy host, this can explain Proteobacteria.10 Culture mainly of the results are required. Previous the occasional detection of viable bac- revealed bacteria of the genera Staphy- studies did not incorporate internal teria at low-abundance in blood and lococcus and Propionibacterium (but controls or only at some stages during tissue samples including the heavily notably not the known human pathogen the experimental procedures (e.g., at perfused placental tissue. It can also S. aureus or any Proteobacteria). They DNA isolation and sequencing) but explain the detection of bacterial DNA at concluded the existence of ‘‘microbial not at sample collection.8,9 A bacterial sterile body sites. Although sensitive to transfer at the foeto-maternal interface’’ composition similar to that found in the nucleases, DNA remains detectable in and the presence of a ‘‘fetal micro- environment or the human oral or skin blood for a certain time and could reach biota’’.10 A recent PCR-based study on microbiota should raise doubts on the the placental tissue with the bloodstream early bacterial airway colonization origin. One study detected a similar or intracellularly in maternal phagocytic demonstrated the presence of a diverse microbial density and bacterial commu- migratory cells. and distinct lung microbiome at birth nity structure in placental specimen and Moreover, the detection of DNA by and also hypothesized fetal microbiota air swabs from the processing room.12 definition is unable to prove the exis- acquisition to explain their findings.11 Two other studies highlighted the simi- tence of a bona fide microbiota. The word Although maternal-fetal transfer of larity of the bacterial spectrum detected microbiota composed of the two greek commensal bacteria would reduce the in placental tissue with the human oral words mikros (small) and bios (life) environmental influence and could microbiome or the skin microbiota.7,8 describes a community of microorgan- thereby help to explain stable transmis- Another way to reveal a contamination isms that colonize an ecological niche sion of the microbiota over many gen- bias is to use different purification and refers to the presence of viable, erations, the currently available data methods with the same samples. A proliferating and metabolically active supporting the concept of a placental defined bacterial community is expected microorganisms. The detection of bac- or fetal microbiota at this point are highly to display a similar composition irre- terial DNA is not necessarily equivalent questionable for the following reasons.