By Andrea Flores Esparza
Planet Earth is probably the wrong place to be if you do not like microorganisms as they are everywhere. In everything that surrounds you, on you and even inside of you. The fact that we are living in a bacterial world—rather than a ‘Material World’ as suggested by Madonna—has been known for many years. However, we understand very little about them even today. Much so that throughout decades it was widely believed that bacterial cells outnumbered human cells in our bodies by approximately a factor of ten, when in reality this ratio was calculated to be one-to-one.1,2 Although the actual ratio of bacteria-to-human cells in our body was calculated to be much smaller it still implies that our bodies are covered in microorganisms, to which we refer to as microbiota and to their genes as our microbiome.
So how exactly did we end up covered in bacteria? The longstanding debate regarding the microbial colonisation of the human body has been in question for many decades, aiming to uncover how this mutualistic relationship came about and thus better understand the role that the microbiome plays in human development and disease. The importance of answering this question lies on the fact that research has found that the microbial colonisation is particularly critical during the early stages of life as they not only programme the child’s immune and digestive systems, but they also seem to influence the development of disease in later stages of life.3
For many years it was largely accepted that humans only came into contact with microorganisms during and after birth in a well-established theory known as the “sterile womb paradigm”.4 This hypothesis argues that a healthy foetal environment is completely sterile and that there is no contact between the mother’s microbiome and her child throughout the pregnancy. However, this would not be called science if there was no evidence challenging this well-established paradigm. Recent studies have provided contradicting results that suggest that the acquisition of microorganisms does occur during pregnancy—providing evidence for their presence in the amniotic fluid, placenta and foetus with the use of novel sequencing technologies.4 This article intends to walk you through the different pieces of evidence regarding the acquisition of microbiota, starting by when we are not (or at least not fully) covered with bacteria—in our mother’s womb.
The arguments in favour of the “sterile womb” hypothesis suggests that, since microbial colonisation in the human body only occurs during and after birth, the different delivery routes would expose newborns to different bacterial environments and thus cause them to a different microbiota composition. There are large amounts of evidence that do not only support this claim, but also suggest that these differences can predetermine a child’s health. For instance, research has found that babies born through C-section are exposed to the mother’s gastrointestinal microbiota as well as hospital-acquired bacteria rather than to the mother’s vaginal microbiota as seen in vaginally born babies.5 Although these differences have been observed to last up until the first six to nine months of life, they have been correlated with an increased risk of obesity and asthma during childhood.6,7,8 If this hypothesis is proven to be correct there would be a completely new attitude towards the clinical practice of C-sections as it will prove them to be disruptive in the microbial colonisation of the human body, subsequently leading the child to have an unhealthy or underdeveloped microbiome that would eventually affect their health.4
On the other hand, the “in utero colonisation” hypothesis, as the name suggests, argues that microbial colonisation begins in the utero and therefore supports the existence of a placental microbiome.4 Studies supporting this claim had sampled, cultured, and analysed different components of the foetal environment, including the placenta, the amniotic fluid, and the meconium, detecting the presence of microorganisms.9 In comparison to studies supporting the “sterile womb paradigm”, these studies incorporate molecular approaches that enable a more precise detection of bacterial organisms in these foetal environments. For instance, Lisa F. Stinson and her colleagues sequenced meconium and amniotic fluid samples from 50 healthy pregnant women with no sign of intra-uterine infection nor other pregnancy complication. They detected bacterial DNA in most of these samples using the highly accurate rRNA gene sequencing technology.9 The bacteria identified was mainly non-pathogenic skin commensals including Propionibacterium acnes and Staphylococcus spp. Nonetheless, despite the evidence provided by this and other similar studies—which have shifted from more traditional approaches to novel technologies in search to identify microorganisms in the foetal environment—have been largely criticised due to its contamination limitations. It is widely known that these molecular sequencing technologies are highly sensitive and thus are highly susceptible to contamination along different stages of experimentation, raising skepticisms regarding its accuracy of this data and thus causing the debate to remain unsolved.
An emerging hypothesis that provides a link between these two contradicting ideas, and thus potentially aid this discussion, suggests that the bacterial traces detected in these studies are antigens presented by the mother’s immune cells (i.e. placental dendritic cells). These antigens are thought to be presented with the aim to prime the foetus’ immune system during development. In their study, Christopher R Wilcox and Christine E Jones found that foetal priming occurred in utero after infection, allergens, and vaccination by detecting antigen-specific cells in the utero and at birth.10 Although this evidence remains controversial and requires further research, it may provide a reasonable answer as to why microbial traces can be detectable using relatively novel and accurate technologies.
Despite the advances made in our understanding of the mutualistic relationship between an adult and its microbiome, there continues to be a gap in our knowledge regarding the acquisition and development of these essential microorganisms and the implications that these processes may have in our future health. Therefore, clarifying this debate is of great interest to microbiologists as it will not only help them better understand the short- and the long-term impacts that the acquisition of our microbiome may have on our human health, but will also guide us to find possible ways to interventions that would ensure that a newborn develops a healthy and complete microbiome. Doing so may also potentially lead to the reduced risk of developing disease throughout childhood and even throughout life, as we would be able to ensure that these newborns are equipped with the right formulation of microbiota to help the immune, digestive and even neurocognitive systems mature adequately.
- Abbott, A., 2022. Scientists bust myth that our bodies have more bacteria than human cells – Nature. [online] Nature. Available at: <https://www.nature.com/articles/nature.2016.19136> [Accessed 18 February 2022].
- Sender, R., Fuchs, S. and Milo, R., 2016. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLOS Biology, [online] 14(8), p.e1002533. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991899/> [Accessed 18 February 2022].
- Koleva, P., Kim, J., Scott, J. and Kozyrskyj, A., 2015. Microbial programming of health and disease starts during fetal life. Birth Defects Research Part C: Embryo Today: Reviews, [online] 105(4), pp.265-277. Available at: <https://onlinelibrary.wiley.com/doi/10.1002/bdrc.21117> [Accessed 18 February 2022].
- Perez-Muñoz, M., Arrieta, M., Ramer-Tait, A. and Walter, J., 2017. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome, [online] 5(1). Available at: <https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0268-4#citeas> [Accessed 18 February 2022].
- Tregoning, D., 2022. Infectious: Pathogens & How We Fight Them. UK: Oneworld Publications.
- Hamzelou, J., 2022. C-section babies have a different microbiome – but not for long | New Scientist. [online] Newscientist.com. Available at: <https://www.newscientist.com/article/2216818-c-section-babies-have-a-different-microbiome-but-not-for-long/#:~:text=Babies%20born%20by%20caesarean%20section,birth%20mode%20on%20the%20microbiome> [Accessed 18 February 2022].
- Huh, S., Rifas-Shiman, S., Zera, C., Edwards, J., Oken, E., Weiss, S. and Gillman, M., 2012. Delivery by caesarean section and risk of obesity in preschool age children: a prospective cohort study. Archives of Disease in Childhood, [online] 97(7), pp.610-616. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784307/> [Accessed 18 February 2022].
- Darabi, B., Rahmati, S., HafeziAhmadi, M., Badfar, G. and Azami, M., 2019. The association between caesarean section and childhood asthma: an updated systematic review and meta-analysis. Allergy, Asthma & Clinical Immunology, [online] 15(1). Available at: <https://aacijournal.biomedcentral.com/articles/10.1186/s13223-019-0367-9#citeas> [Accessed 18 February 2022].
- Stinson, L., Boyce, M., Payne, M. and Keelan, J., 2019. The Not-so-Sterile Womb: Evidence That the Human Fetus Is Exposed to Bacteria Prior to Birth. Frontiers in Microbiology, [online] 10. Available at: <https://www.frontiersin.org/articles/10.3389/fmicb.2019.01124/full> [Accessed 18 February 2022].
Wilcox, C. and Jones, C., 2018. Beyond Passive Immunity: Is There Priming of the Fetal Immune System Following Vaccination in Pregnancy and What Are the Potential Clinical Implications?. Frontiers in Immunology, [online] 9. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054988/> [Accessed 18 February 2022].