Does how you're born affect your microbiome?

It’s now well understood that we’re not alone in our bodies. Trillions of microbes collectively known as the human microbiome live in us and on us, and make a major contribution to keeping us healthy. But how do newborn babies acquire their microbiomes in the first place, and how does the way you are born, or exposure to antibiotics potentially affect things? Peter Brocklehurst is based at the University of Birmingham where he’s a consultant in Public Health and studies these questions as part of an initiative called the Baby Biome Study, and he spoke with Chris Smith. First, Chris asked, what's the Baby biome study seeking to find out?

Peter - Well, we know that mode of birth, particularly cesarean section when compared with vagina birth is associated with conditions in childhood such as asthma and eczema and possibly early-onset diabetes. And the mechanism that links those early exposures to those later outcomes could be through their microbiome. So we know that babies are born without any organisms on them or in them and their first exposure is at the time of birth. If those organisms that colonise the babies gut are different between a cesarean section and vagina birth then that may be the mechanism by which that risk leads to the late outcomes for the baby.

Chris - How are you doing the study?

Peter - So we've taken samples of maternal poo, we've taken samples of baby poo with taken cord blood and we've taken the vaginal swab samples, and then of course we've linked all of those together and we're following up those babies. So with analysed the poo samples, in particular taken at day 4, 7, 21 and between 6 and 10 months and then we are looking at the organisms that we find and linking those together, ascribing them to the mode of birth of the baby.

Chris - So at the moment the association that we know of, the one you mentioned is that you've taken people whom we know were born by cesarean section and we've said these individuals have an elevated risk of asthma, other allergies and intestinal diseases, but we don't know what role the microbiome is playing. Here you're saying you're going to follow these individuals having got a cross-section of the microbiome at these different ages to see if they develop those conditions and then we can actually ask whether one causes or is profoundly linked to the other?

Peter - Correct.

Chris - With your initial findings with the data you have so far, what actually emerges when you compare the microbiome of babies born via cesarean section and those born vaginally?

Peter - Well, for those born vaginally, perhaps not surprisingly, we're finding organisms - the initial colonising organisms to be very similar to those that their mothers carry because babies are born obviously with their mouth close to their mothers anus and that's probably where they pick up the organisms and get that initial colonisation. For babies born by cesarean section, we always rather hoped that the organisms they were first exposed to will be those on their mothers skin and their mother's breast, and those would colonise the babies gut.

What we're finding however is that those babies born by cesarean section have a very different microbiome pattern than those delivered vaginally, including a lot of pathogenic organisms which are those which you would find in hospital-acquired infections. Of more concern is that those hospital-acquired organisms appear to be persistent so even at 6 to 10 months we're finding high levels of those organisms, many of which are resistant to antibiotics so antimicrobial resistant organisms are persisting at 6 to 10 months. So that's quite a lot of concern.

Chris - Indeed, some people say that babies born vaginally their first taste of life is a mouthful of muck. Their mums muck but it's probably the most important meal there ever going to eat because it does seed to their microbiome in this way. I suppose it's worth considering that if you've got a cross-section of microbes that aren't quite the ones that ought to be there, as in you've got hospital superbugs and things, they might be there at low level for what they might be doing is suppressing the growth of other microbes that you do need and which are beneficial to your health so it's not just the physical presence of some bacteria, it might be also that they're causing an absence of other critical ones?

Peter - Well I'm not sure that's true. We are finding obviously babies who are born by cesarean section do digest proteins in milk, whether it's breast milk or formula milk, and so there are organisms in there doing the activities that they're supposed to do. It's a very complex system of organisms living in the gut. The issue about which are the initial colonisers however is that babies are born without anything, without any organisms inside them so the first one is a become exposed to they recognise as being normal and they don't get rid of them and therefore they can become persistent. So even if they're only there in low levels, if they've got antimicrobial resistant pathogenic organisms, those could cause disease disease for them for other people later in life - we just don't know that yet.

And one of the reasons we don't know that is that, until quite recently, we used to give all women, we give all women now who are having a cesarean section broad-spectrum antibiotics to limit the risk of them developing a wound infection. We used to give those antibiotics after the baby had been born by cesarean section after the cord had been cut, so none of those antibiotics got through to the baby. Because their recent evidence suggest that by giving the antibiotics earlier we might slightly decreases the woman's risk of wound infection. We're now giving high dose, broad spectrum antibiotics before the cord is clamped, and so though babies are being born not only by cesarean section but with high-dose of antibiotics on board. So that may have a double whammy if you like in terms of their exposure to organisms, again selecting out the antibiotic resistant and abnormal bacteria which can become established as normal.

Chris - Since you brought up the subject of antibiotics, may we therefore venture into the territory of a baby that’s born the normal way but develops some kind of infection or is exposed to something that means it ends up needing a big dose of antibiotics in the first year of life. Are you also looking at that and what might be the consequences because that too could distort the microbiome considerably couldn't it?

Peter - Yes, and we know that it does. So again, from epidemiological studies, we know that children who are given antibiotics within the first six months after birth, compared with those given after the first six months but within the first year, those given it early are at a much higher risk of developing childhood obesity than those given later antibiotics. Again, the mechanism for all of this is not clear, it's thought to be the microbiome and we do know that antibiotics have a profound effect on the microbiome development.

For you and I, if we are given antibiotics it does affect our microbiome but over time that microbiome will drift back to the state it was before because our bodies are used to and tolerate the organisms that we have in our gut because we recognise them as normal.

One of the theories is for newborns until they've developed that tolerance, you can knock the trajectory in a completely different direction by giving them antibiotics early, killing of some of the bacteria and allowing others to grow and therefore you send the baby's microbiome in a completely different trajectory and it never gets back to where it was before.

But we're really in the very early days of understanding this and it's a highly complex ecosystem in our gut so I don't want to make too many assumptions about what we're going to find, but I think there are concerns about the very widespread use of antibiotics around birth and early life, that could have quite severe consequences which might not manifest for many many years to come.

Chris - Indeed. One has to be conscious of the fact that antibiotics save lives don't they and we owe them a great deal, but at the same time we must not become too profligate because there may be unintended consequences?

Peter - Exactly. And if a baby absolutely needs antibiotics, it needs antibiotics. We don't want women getting lots of infections because we’re not using antibiotics appropriately, but I think the balance between using enough antibiotics and not using too many is quite a difficult one, and we need to get that balance right. So we limit our use of antibiotics to where it's absolutely essential and limit our exposure to when it's potentially quite nice to have, we think, but it could be potentially harmful. And it's that balance that is quite difficult to achieve.

Chris - So what can health professionals do? Because there are reports in some countries of investigations about the possibility of seeding babies that are born by cesarean section with what we dubb the right sorts of microbes by taking swabs from the mum and then spreading them into the baby's mouth as one way, perhaps, to get the baby colonised with the right sorts of microbes early?

Peter - Yes. And lots of people are doing that. It's mostly driven by women and parents rather than health professionals. I think, in general, health professionals are quite anxious about this procedure. Everything I've said about the microbiome is still theoretical. We are finding these interesting effects in the microbiome, but we don't know yet that they will inevitably lead to disease or problems.That's the hypothesis and we want to explore that further.

But in the meantime we are concerned that vaginal seeding could introduce one particular organism which about 1/4 of all women carry in their vaginas, which is group B Strep, which can be extremely serious. It's very rare that it causes disease but when it does these babies can get very sick and die very rapidly.

So we feel uncomfortable suggesting that women should do vaginal seeding because, of course, if that causes a baby to get sick and die as a consequence of addressing a theoretical impact on the microbiome, then that will be catastrophic.

So we do need to understand the processes better, we do need to understand the mechanisms, and we need to understand if we're going to get to the stage of using bacteria therapy in babies born by cesarean section, that we use the right bacteria in the right way, in a more controlled way, so that we don't make things worse, we make things better. But that, I think, is quite a long way in the future.