Of the placental microbiome

fetusA study published last week in Science Translational Medicine shows that low amounts of DNA from diverse bacterial phyla are found in the placenta even in healthy pregnancies, and that the bacterial phyla present in the placenta are more similar to those found in the mouth than to those present in other body tissues such as the gut, the skin, or the vagina.

Many news outlets reported the findings; unfortunately, it seems that (perhaps characteristically) the speculations developed by the authors of the study in the discussion section of their article received more attention than the actual results of the study, leading to misleading comments on the importance of oral hygiene in women and on the relative importance of the placental microbiome and the mode of delivery (C-section or vaginal birth) regarding the infant’s own microbiota.

  • The placental microbiome – what the study shows

First of all, this study is not the first one showing that there are bacteria in the placenta. What the researchers have done here is to look in more details at what kind of bacterial genetic diversity there is.

The team collected bits of placental tissue at the time of delivery from a total of 320 pregnancies, isolated DNA from these samples and analyzed them for the presence of bacterial DNA. 48 samples were subsequently analyzed in more details through a technique called whole-genome shotgun sequencing. The researchers then looked at the relative abundance of DNA from different bacterial phyla in the placental samples and compared it to what had been described for other body sites harboring bacteria.

The amounts of bacterial DNA isolated from the placental samples was relatively low but nevertheless revealed the presence of a diverse set of bacteria. Escherichia coli was the most prevalent single species in the placenta of most individuals, but the tissue samples also contained DNA from other bacterial phyla. Comparison of the different phyla present in the placental tissue and their relative abundance with those present in other tissues showed that the taxonomic profile of the placental microbiome was more similar to that of the mouth microbiome than to those of the gut, skin, or vaginal microbiomes.

The research team also compared the diversity of bacterial phyla making up the placental microbiome between samples from full-term and pre-term deliveries (less than 37 weeks of pregnancy), and between samples from pregnancies with and without clinical history of antenatal infections. They found that the bacterial taxonomic profile of the placenta varied with gestational age at delivery, and that the relative abundance of certain kinds of bacteria was different between women with a history of bacterial infection in the first or early second trimester of pregnancy and women with no clinical record of infection.

  • The placental microbiome – questions and speculations

As with any scientific result, the data presented in the Science Translational Medicine article have their share of limitations, but they are also a source of new knowledge on which further research can be build, generating questions and hypotheses to be investigated. That is how it should be. However the study garnered a fair amount of press coverage (sexy microbiome’s fault?) and many stories went a bit overboard in their claims. Here are some of the questions/issues I noticed.

Is there really a placental bacterial community?

The researchers assessed the diversity of bacterial phyla present in the placental samples via sequencing DNA isolated from these samples, hence the use of the term “microbiome” to refer to the collective microbial genomes present in the samples, rather than “microbiota”, which would refer to the microorganisms themselves. However, showing the presence of bacterial DNA is not the same as showing that there is a living microbial community in the placenta. In addition, the amount of bacterial DNA isolated from the samples was relatively low, so is it possible that the bacterial DNA found in the placental tissue was from the maternal blood flow rather than from an established local microbial community? In any case, it seems a bit too early to talk about a placental ecosystem teeming with bacteria based on just the data presented in this study.

If there is a placental microbiota, where did the bacteria come from?

This particular study explores the bacterial genetic diversity present in human placenta but does not provide data to address the question of how a living bacterial community would be established in the placenta. From the fact that the taxonomic profile of the placental microbiome resembles more that of the mouth microbiome than those of the skin, gut, or vaginal microbiomes, the authors of the study suggest that the placental microbiome is established by the spread of the oral microbiota through the maternal bloodstream. However it is also possible that bacteria are already present in the uterus before pregnancy and contribute to the placental microbiome.

The oral hygiene emphasis

Based on the resemblance between the placental microbiome profile and that of the mouth microbiome, the researchers speculate on a possible link between periodontal disease, placental microbiome, and preterm deliveries. Although this is enough for many news articles to emphasize the importance of oral hygiene during pregnancy, there is no data in the study causally connecting periodontal disease, the composition of the placental microbiome and pre-term births. For one thing, only one of all the placental samples analyzed came from a woman with periodontal disease (the majority of women with a clinical history of infection during pregnancy had been treated for urinary tract infections or a sexually transmitted infection – gonorrhea or chlamydia). But even considering other types of infections, there is no data in the study allowing to draw a causal link between infections and preterm deliveries that would be due to a change in placental microbiome composition. Making variation in the placental microbiome composition responsible for preterm deliveries associated with maternal infections is therefore a big leap to make based on this sole study (a leap probably motivated by the current hype surrounding anything that has to do with the microbiome), and one that actually ignores the fact that infections would affect other parameters that could have an effect on pregnancy besides the placental microbiome composition (for example, an increased inflammatory response in the mother).

Placental microbiota responsible for preterm births?

I have also seen headlines suggesting that bacteria present in the placenta could be responsible for preterm deliveries (even without bacterial infections in the mother). Again, quite a leap from what the study shows. Although the researchers did observe a difference in the relative abundance of the different bacterial phyla present in the placenta between samples from preterm deliveries and samples from deliveries at term, they do not show any data supporting a causal link between placental microbial composition and the risk of premature birth (as always, correlation is not causation). Also, as the authors themselves mention, the composition of the placental microbiome earlier in pregnancy for women who delivered at term is unknown (it would have required an invasive procedure and sampling of the placenta during pregnancy), so one cannot dismiss the possibility that the composition of the placental microbiome simply changes over time during a healthy pregnancy, without being causally related to gestation length.

Placental microbiome and infant microbiota

This study did not look at the microbiota present in infants shortly after birth so nothing (but speculations) can be said here about a potential transmission of microbes from mother to fetus via the placenta. The idea of such a mother-to-fetus transmission is however not new (see an older post on the topic here), though difficult to investigate in humans.

The techniques employed in the present study to analyze the placental microbiome were based on DNA sequencing, so whether the placenta harbors living bacteria that can be passed on to the fetus during pregnancy remains unknown. There may very well be a transfer of bacteria from mother to fetus in utero, and a study done in mice has indeed found so. However, if science news stories want to suggest the existence of such a maternal microbial transmission to the fetus, they should do so by citing the relevant scientific evidence, certainly not on the basis of a study that presented data on genetic microbial diversity in placenta but that in no way investigated the transfer of living microbes from mother to fetus.

That being said, even if bacteria were found to pass from mother to fetus via the placenta, it would not change the fact that the make-up of an infant’s gut microbiota is affected by the mode of delivery (vaginal birth versus cesarean section). Studies on the topic have generated data supporting this latter idea, and in parallel, others have shown that babies delivered by C-section have a higher risk of developing immune-related disorders later in life than babies delivered vaginally. To suggest that a (possible) transfer of microbiota from mother to fetus during pregnancy could “reassure” women opting for a C-section delivery that there will be no effect on their infant’s microbiota does not make any sense: only finding that the mode of delivery does not affect the baby’s microbiota could provide such “reassuring” evidence (and this is independent on whether bacteria have been transferred to the fetus before delivery or not), and so far, studies have shown the contrary.

  • Scientific article versus science news story

I had originally looked at this study because I found its investigation of the placental microbiome interesting. Then I noticed the science news articles building on the “microbiome” hype to sell stories with headlines that went far beyond what the original scientific paper reported. Although the authors were more cautious in what they wrote down in their Science Translational Medicine article (which goes through peer-review), it seems that they were driven to go further in their speculations when interviewed by journalists. Some of the limitations of the study that were appropriately discussed in the scientific article were also absent from the science news reports available to the public, and emphasis was put on the speculations made by the authors at the end of their scientific article, often misleadingly representing them as being more than just speculations that have yet no evidence to support them.

But then, would readers have cared for a science story that had nothing sensational to reveal?

For more on the not-so-great science reporting surrounding this particular study, look at this post on Jonathan Eisen’s blog: Overselling the microbiome award – many – for stories about placental vs. oral microbiomes.

Reference
The placenta harbors a unique microbiome. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. Sci Transl Med. 2014 May 21;6(237):237ra65. doi: 10.1126/scitranslmed.3008599
PMID: 24848255

ResearchBlogging.orgAagaard K, Ma J, Antony KM, Ganu R, Petrosino J, & Versalovic J (2014). The placenta harbors a unique microbiome. Science translational medicine, 6 (237) PMID: 24848255

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