The placenta is not a hermetic shelter as was once thought. Recent research shows it harbours a unique ecosystem of bacteria coming from the mother. And alterations of that microbial community, claims Kjersti Aagaard of Texas Children’s Hospital and Baylor College of Medicine in Houston (USA), may lead some women to give birth prematurely. Aagaard investigates the impact of gestational factors on birth and also on the early life microbiota. She has looked at how, for instance, the mum’s diet can affect her infant’s gut bacteria and thus, disease risk.
At the beginning of the summer, Aagaard attended the Barcelona Bdebate conference on the human gut microbiome, held at the Cosmocaixa Science Museum on June 30 and July 1.
Tell us about your research interests – so far your research focuses mostly on what factors in pregnancy impact the early life microbiota.
Where we are really looking to expand our interest out is in those first weeks to months of life. We know something about what the baby’s microbiota looks like at birth and we know something about what it looks like even at a year. But we firmly believe it is crucial to understand the first six weeks of life, when there are minimal outside the home and family exposures.
What do you mean by exogenous exposures?
Many babies by 6 weeks of age are in daycares. By two months of age they get a whole round of vaccines; a significant percentage of them will have got an additional antibiotic course; some of them will be exclusively breastfed, other[s] will have formula milk, or a mix of both. And so on. That’s why we think this first window is so pivotal. We need to understand that relatively naïve period and the impact of pregnancy on it. And in fact, part of our research focuses on trying to discriminate out whether we can measure the impact of the 40 weeks of [pregnancy] in those first six weeks of life.
And that is where our interest differs from some other group[s]. Ours relies mainly in understanding the role pregnancy plays in modeling that early microbiota, whereas other groups are interested in understanding what the early interval of time means for life down the road. Both are separate questions and we look at [the same period] in very different ways.
During pregnancy, it has been discovered, some of the mum’s bacteria get to the placenta. One hypothesis states the reason for this bacterial journey is to start preparing the fetal immune system.
Let me be a bit skeptical. Bacteria circulate in blood through our bodies, also into the placenta, and [they cross] into the fetus. I am not sure there is a huge evolutionary design thing of having bacteria there, but it is just a process of blood flow that just happens. Having said that, it is true we can maybe take advantage of it; there may be ways we can leverage that exposure early on [in] life. Why not start preparing the body defense system?
In fact, you have a paper on the placenta microbiota suggesting that idea.
We have, but it was just speculation. Recently, there was a paper published suggesting this purpose for bacteria crossing the placenta. In a mice study, researchers used a pathogenic form of E. coli to demonstrate mum’s bacteria start training the baby’s immune system. It could be. But we don’t know what came first: the bacteria or the immune system.
You talk about these 40 weeks of pregnancy and the impact they have on the baby’s microbiota. But what about, for example, the mode of delivery or antibiotics used during labor or in early life?
We have a paper in review just now that tackles just this. There are a lot of women that during labor need to get a course of antibiotics for a myriad of reasons. In the States, for example, we screen all women for Group B Streptococcus; in [the] case they are positive, they need to get a course of antibiotics, because these bacteria can be passed on to the baby during labor or birth. It is harmless in adults but may cause stillbirth, and serious infections in the newborn.
As a clinician, I think we should take a pause for a moment, when talking about the impact of antibiotics (AB) in babies’ microbiota, and [remember]: first, we do a lot of things in labor management, and take a lot of decisions around pregnancy that have nothing to do with microbial health, but with the mum’s or the baby’s health. For example, there is good and solid evidence that the best thing to do before a caesarean is giving AB to the mother. In fact, it is crucial to give a course of AB before you cut anyone’s belly for any reason. Not doing so has negative consequences. In the case of caesarean, antibiotics prevent wound infection, at extreme states sepsis, endometritis.
So we have to be very cautious when taking large cohorts of associative data and conclude not to give AB during labor or even not to do Caesareans.
So your recommendation would be caution.
Of course. These are highly confounding things and many factors go hand in hand clinically. Discerning what has a real long-lasting impact is crucial before we change what we do now in our clinical practice for medical good reasons. Because antibiotics and caesarean are saving mothers and babies’ lives, reducing morbidity and mortality.
Can you tell us about the recent paper from the Broad Institute that shed some light on C-section’s impact on early life microbiota?
They followed 39 babies since they were born until they were three years of age. Four of them were born by C-section and what was interesting was that they found that not only babies born by C-section had low levels of Bacteroidetes but so did at least 20% of the vaginally born babies. In fact, they could not discriminate between those ones. In my opinion, we have attributed certain things to C-section delivery but have not paid attention to what happened before, the prior 40 weeks of pregnancy, and maybe that is as important or even more than how the baby comes out.
I don’t believe that the way in which you are born, C-section or vaginally, can determinate how your microbiota will look like during your life [although] maybe it has some burden.
Can breastfeeding reconstitute that early microbiota?
Breastfeeding is really important. The American Academy of Paediatrics, and the WHO are very clear about it: women should exclusively breastfeed through at least the first 6 months of age, without mixing formula milk. Its health benefits are very well known and documented. Unfortunately, not all women can do that. Ideally, they can even use milk banks.
But, whether breastfeeding can restore the microbiota of the baby, we don’t really know the answer yet. But we have good evidence babies exclusively breastfed do have different microbiota composition. But, again, caution. Looking at the relative levels of this or that bacteria is a far cry from understanding the whole metabolic and immune health [of] a child.