Vol. 25 No 4 | Summer 2023
Microbial maternity: the importance of the gut microbiome in pregnancy
Prof Peter Vuillermin
Director of Research, Barwon Health Chair in Medicine, Deakin University

In 2009, a group of renowned scientists proposed a set of ‘planetary boundaries’ within which humanity must remain to develop and thrive.¹ These relate to climate change, ozone depletion, atmospheric aerosol loading, ocean acidification, freshwater change, land system change, biogeochemical flows, and biodiversity. In the broader context of reducing biodiversity of the macro and microenvironment, we should consider the importance of the human microbiome during pregnancy.

The combined genetic material of microorganisms within a particular environment is known as the microbiome. We have co-evolved with our microbiome; consequently, it plays a non-redundant role in human health. Most human commensal organisms are found in the gut, where they contribute to the digestion and metabolism of food to produce biologically active molecules critical to gut wall integrity, immune homeostasis, brain function and cardiometabolic health. Recent studies suggest that approximately half of the bacteria in a traditional human gut microbiome are no longer present in communities living in the industrialised world,² and there is intense interest in determining the extent to which depletion of the maternal gut microbiome impacts pregnancy complications and infant outcomes.

Technical advances have enabled rapid advances in understanding the microbiome in health and disease. We have progressed from early cataloguing studies toward an increasingly robust understanding of mechanisms and, more gradually, toward robust evidence of causality.³ Numerous diet-by-microbiome pathways have been described. Best known are the processes by which plant-derived complex carbohydrates, or fibre, are metabolised by gut anaerobic bacteria to produce the short-chain fatty acids (SCFAs) acetate, butyrate and propionate.⁴ SCFAs provide a nutrient source that promotes gut wall integrity, they promote the production of regulatory T cells (Treg) that control excessive inflammation, they impact immune cell precursor development in the bone marrow, and they promote immune regulation in distal organs such as the lung. Moreover, SCFAs cross the placenta and impact fetal development.⁵

The pathways by which commensal bacteria in the gut metabolise plant-derived polyphenols to produce many anti-inflammatory and antioxidant molecules are less known. Over 8000 types of polyphenols have been identified, many of which convey biological benefits. Dietary intake of polyphenols-rich foods, such as fruits and vegetables, in combination with the metabolic competence of the gut microbiome, is likely to be crucial.⁶

The immunological mechanisms enabling the mother to grow a genetically foreign fetus over the course of pregnancy is an evolutionary masterpiece. Unsurprisingly, diet-by-microbiome pathways might impact these processes and, in turn, the depletion of specific diet-by-microbiome pathways may be critical. In the Barwon Infant Study (BIS), we found a lower concentration of SCFAs in the serum of women who subsequently developed pre-eclampsia.⁷ Moreover, the infants of women who developed pre-eclampsia had a lower proportion of thymic-derived Treg at birth, and this persisted until at least 4 years of age. Our collaborators went on to show that the offspring of germ-free mice have a strikingly underdeveloped thymus that can be rescued by the administration of SCFAs via the mother’s drinking water during pregnancy.⁷ Whether diet-by-microbiome pathways can be targeted to prevent preeclampsia is the subject of ongoing research.

Maternally derived IgG carrying small bacterial fragments across the placenta to impact the fetal immune system might also be crucial. In an elegant study, it was shown that colonisation of the germ mouse with the bacteria Escherichia coli during pregnancy had a profoundly beneficial impact on the infant’s developing immune system and their susceptibility to postnatal infections.⁸ Intriguingly, serum taken from an E. coli colonised mouse could rescue the immune development of a germ-free pregnancy, but not if the IgG were removed from the serum. IgG is both passively and actively transported across the placenta carrying bacterial epitopes, or fragments, and is therefore ideally placed to prepare the developing baby for the microbial environment it will face during and following birth.

Prenatal fetal immune programming is likely leveraged following birth to enable efficient postnatal immune development and regulation.⁹ Infants born to mothers living in more diverse microbial environments, such as a farm with livestock, have greater expression of innate immune receptors at birth, presumably enabling more efficient interaction with their postnatal microbial environment. The resulting efficient and well regulated responses to infectious challenges, such as respiratory viruses, might contribute to the low rates of wheezing illnesses among children in traditional farming environments, such as among the Amish.10

In Australia, approximately 10% of babies develop clinically proven IgE-mediated food allergy, and approximately 20% will subsequently develop asthma.11,12 These are among the highest rates in the world. The maternal microbiome may be critical in preventing allergic disease and asthma in the infant.⁹ In BIS we found that maternal carriage of the commensal bacteria Prevotella copri is associated with protection against food allergy and the infant.13 The genus Prevotella is an archetypal symbiont virtually ubiquitous in hunter-gatherer communities, such as the Hadza in Tanzania, which is becoming increasingly uncommon in the industrialised world.14 The underlying basis of the association between maternal carriage of P. copri and protection against allergic disease remains unknown. Prevotella might be intrinsically impactful, or alternatively, it might be a biomarker of a less industrialised gut microbiome.

There is also mounting interest in the role of the maternal microbiome in fetal brain development and subsequent behavioural and neurocognitive outcomes of the children. For example, we produced the first human evidence that a healthier dietary pattern was associated with improved child behavioural outcomes via increased diversity of the mother’s gut microbiota during pregnancy.15 Indeed, there are now numerous studies underway investigating the potential role of the maternal microbiome in the prevention of adverse neurobehavioural outcomes in children such as autism and attention deficit hyperactivity disorder.

It is an exciting area but also essential to acknowledge some critical limitations of the microbiome field. Some 500 microbiome papers are published monthly, yet examples of translation to clinical and public health impact are difficult to find. The majority of human research is observational and associative. Most experimental work has been conducted in highly artificial environments, with animals that generally have microbiomes that are very different from humans.³ In this context, we must support research that combines high-quality longitudinal research in human cohorts with cutting-edge mechanistic work and experimental research. We need large-scale, high-quality randomised control trials of interventions addressing microbiome-immune pathways during pregnancy. Good examples of such trials include the SYMBA Study assessing a prebiotic supplement for the prevention of infant allergic disease,16 and the recently funded Bugs and Bumps trial, which is being conducted within Deakin University Pregnancy Research and Translation Ecosystem (PRT-E).17

So, what then are the currently actionable clinical and public health messages regarding the microbiome during pregnancy? A high-quality diet is associated with benefits in a range of maternal and infant outcomes, and some of these benefits are likely to be mediated by diet-by-microbiome pathways. What is a high-quality, microbiome-friendly diet? Well, it is one that your great, great grandmother would recognise: it is high in vegetables, fruit, legumes, and fish. Equally important, it is low in highly processed foods and simple carbohydrates. An excellent way to improve diet quality is to be involved in the local production of fruit and vegetables, either at home or as part of a community. Minimising unnecessary exposure to antibiotics is also important. Antibiotics can be life-saving when used to treat a serious bacterial illness, but unfortunately antibiotics are overused in many countries, including Australia, impacting both ecological diversity and antimicrobial resistance patterns. Moreover, misuse of antibiotics is a critical issue in the industrialised food system – another excellent reason to prefer locally grown, organic food. A healthy intake of fermented foods such as yoghurt and fermented vegetables is also likely beneficial. There is inadequate evidence to suggest routine supplementation of specific gut bacteria with currently available probiotics, but this is a fast-moving space. Consider participating in a diet-by-microbiome clinical trial, as these are crucial to testing and translating the potential of the microbiome field.

Pregnancy is fundamentally about nurturing the next generation. In this context, we can take comfort in the knowledge that a microbiome-friendly diet is not only colourful and delicious, not only does it decrease the risk of pregnancy complications and benefit the baby’s early life growth and development, but it is also a diet that is associated with environmental benefits that are crucial to tackling ecological crisis our children will inherit.


Conflict of interest

Financial interest in the biotech company Prevatex, seeking to develop next-generation probiotics.


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  17. The Pregnancy Research and Translation Ecosystem. Available at

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