The mother’s microbiota and baby’s health, during pregnancy and at birth

How does the mother’s microbiota affect the child’s health and in particular its immune development?

Let’s take a step back first, what is meant by microbiota?

Simply put, the microbiota is that set of microorganisms that coexist with our body. We find them in the skin, mammary glands, placenta, seminal fluid, uterus, ovarian follicles, lungs, saliva, oral mucosa, conjunctiva, biliary tract and gastrointestinal tract. Human microbiota types include bacteria, fungi, protists, and viruses.

In common parlance we speak of resident bacterial flora , a term that is not exactly correct, but which we report anyway to give an idea of ​​what we are talking about.

How many microorganisms reside in our body?

A set of microorganisms live in our body in a symbiotic way, we receive benefits from their presence and vice versa. The best known and most cited is certainly Escherichia Coli. The traditional estimate is that the human body is inhabited by ten times as many non-human cells as human cells, but more recent estimates have reduced that ratio to 3:1 or even about the same number. In any case, it remains a very high number if you consider that the human body on average is made up of about  100,000 billion cells (this number is very variable because it depends on the person’s height, weight, gender, age and state of health ).

Some microorganisms that colonize human beings are commensal, in the sense that they coexist without harming the human being who hosts them; others have a mutualistic relationship with their hosts. Conversely, some nonpathogenic microorganisms can harm hosts through the metabolites they produce.

Some microorganisms perform tasks that are known to be beneficial to the human host, but the role of most of them is not well understood . Those that should be present, and which under normal circumstances do not cause disease, are sometimes considered normal flora or normal microbiota .

The mother’s microbiota and the effects on the child’s health

The mother-child bond is expressed in many ways, what we are going to analyze closely is the transmission of the microbiota from mother to child, a passage that has many important implications for the future health of the child, many of which are yet to be discovered.

A microbial connection is established between mother and child in the first moments of life, when the child’s skin comes into contact with the microorganisms (the maternal microbiota) that inhabit the mother’s body.

This initial microbial exposure creates a specific microbiota in the child that has a fundamental influence on its development and health, even in the long term.

Understanding this microbial link has shed light on host-flora mutualism and immune development in early childhood . At the same time it has made it possible to understand how some characteristics and diseases are transmitted through the generations.

The first contact with the maternal microbiota

In humans and other mammals, the first microbes encountered in infancy are those that belong to the maternal microbiota. It is not yet clear what the initial moment is, whether already during intrauterine life or at the time of delivery.

Fetal development was originally thought to occur in a sterile intrauterine environment. This hypothesis was initially challenged by the discovery of bacterial genomic DNA within the placental and chorioamniotic tissues, and by the presence of microbes in the meconium of the newborn. A new study recently  found that the human placenta lacked a microbiome (although they did find potential pathogens), so exposure to maternal bacterial flora in utero remains a matter of debate.

What is clear however is that the microbiota of the newborn is determined at the time of delivery through contact with maternal bacteria (natural, non-pathogenic) that inhabit the birth canal. Cesarean delivery, on the other hand, involves contact with skin microorganisms.

The contact between the maternal microbiota and the newborn leaves a lasting imprint on the offspring’s biology. Many studies, conducted in both humans and mice, have highlighted links between the composition of the maternal microbiota and the subsequent risk of childhood diseases, including infections, asthma, allergies, autoimmunity and metabolic diseases such as obesity and diabetes.

It has also been seen that the presence of pathological alterations in the composition of the maternal microbiota (alterations that are called “dysbiosis”), can confer susceptibility in the child to a variety of chronic health conditions in adulthood.

As you can see in the figure, the composition of the pregnant mother’s intestinal microbiota changes during pregnancy. A lean woman is supposed to have a stable and healthy gut microbiota that is modulated over the course of pregnancy. How it is transferred to the baby is still unknown, but it may facilitate normal intestinal development and metabolic function in the offspring. Obese women probably have a modified intestinal microbiota (dysbiosis) already before pregnancy, and this alteration is amplified or further modified during pregnancy. These changes lead to an abnormal intrauterine environment that could lead to impaired fetal gut development and an increased risk of metabolic diseases such as obesity.

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The “contamination” with the maternal microbiota continues even during early childhood. For example, breastfeeding serves as a continuous source of maternal microbes, as well as providing nutritional and antimicrobial factors that continuously shape the infant’s gut microbiota.

However, it is not only the intestinal microbiota of the child that feels the influences of the maternal one. There is  recent evidence of a microbiota-mediated gut-brain axis controlling neuroimmune development and susceptibility to neurodevelopmental disorders (eg, eutism) and psychiatric illness.

The role of the maternal microbiota during pregnancy

Before birth, the maternal microbiota is separated from the developing fetus by the physical barriers represented by the placenta and the amniotic sac. However, data from animal studies indicate that the composition and metabolic function of the maternal microbiota is reflected in the immune development of the fetus.

Studies in this sense are complicated to perform and interpret even in mouse models. An interesting study conducted on mice has shown that the normal development of the fetal immune system depends critically on the signals received from the maternal microbiota . The maternal microbiota would prepare the intestinal epithelium and mucosal immune system in the developing offspring for the onslaught of microbial exposure at birth. Extending these findings to human biology will require further research and new methodologies to define the gestational impact of the maternal microbiota on fetal development and childhood health and well-being.

Future prospects

While much has been learned about the maternal microbiota in pregnancy and early childhood, many fundamental questions still remain. In fact, it is not clear whether this information can be used to prevent and treat childhood diseases. To do this, are therapies with live bacterial flora necessary or will specific bacterial products or metabolites (and if so, which ones) be sufficient?

Further research is also needed to determine whether there is a “normal” maternal and early childhood microbiota to target or whether microbial therapy requires specific individualisation.

Furthermore, what are the ethical considerations of therapeutic modification of an unborn fetus through manipulation of the maternal microbiota and what are the potential for unexpected adverse effects?

To answer these (and other) outstanding questions, studies need to investigate the cellular and molecular mechanisms that mediate microbiota-host interactions in pregnancy and early childhood. All of this presents an exciting challenge for scientists to sharpen their understanding of this fundamental aspect of human biology, and an opportunity to apply this cutting-edge science to improve maternal and child health.

In the meantime, all we have to do is try to “cultivate” the good bacterial flora through the right diet, and possibly resort to probiotics in case of imbalances/dysbiosis which, as we have seen, can have negative effects on the child and affect his health from adult.