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September 16, 2020 by Siobhan Campbell | UC Science

Exploring the microbiome and its relationship with infant health

(Image: Quinn Dombrowski/Flickr)

UC Psychology PhD student Siobhan Campbell discusses the relationship between gut health and mental health, focusing on where it all begins… at birth!

For the past several years, through the NUTRIMUM study, Te Puna Toiora | UC’s Mental Health and Nutrition Research group has been investigating the effect that micronutrient supplementation, and maternal depression and anxiety can have on infant development. One of the aspects of interest in this research has been the collection of microbiome samples from mothers and infants, in order to see whether the bacteria found in the gut might be an area of further interest in the realm of antenatal and infant mental health.

First of all, what actually is the microbiome?

The microbiome is defined as the trillions and trillions of microbes and bacteria that are found in the human digestive tract.

Think of the inside of your gut as a small self-sufficient neighbourhood. You’ve got a local doctor, a fireman, a grocery store owner and a teacher – all carrying out vastly different duties, but are all equally vital to the running of the community.

Our guts are like a little neighbourhood of microbes, instead of doctors and firemen, we have different strains of bacteria.

Each of these bacteria are involved in the important role of food digestion, immune and metabolic functioning within the body, and even can play a role in the expression of health and psychiatric symptoms, through the well-established gut-brain connection.

Why are we interested in it?

A decade ago, not a lot was known about the microbiome and its connection to other systems within the body. Recently, this field has become much more widely researched, and several researchers have suggested there may be a relationship between our gut and physical and mental health symptoms.

The bacteria being found in the gut of rodents seems to have a connection to their brain, as it seems to affect the way the rodents are behaving. Because of these initial findings, scientists are continuing to explore the link between what’s contained within our gut to a number of other processes within the human body.

The microbiome is constantly changing over the course of our life, but like many other things in our bodies, the foundation of our gut bacteria starts in infancy.

What factors can affect an infant’s microbiome?

The first three years of life are the most important when it comes to the development of gut microbiome, as an infant is born with a gut composition much less diverse than that of an adult. Gut colonisation can be influenced by a number of maternal and neonatal exposures, both prenatally and postnatally. Some of the factors that can influence an infant’s microbiome, including method of delivery, antibiotic exposure, and maternal mental health are discussed below.

Method of delivery

How a baby is born can have a profound impact on their microbiome. When we are born, our intestines are thought to be mostly sterile, as the womb is a sterile environment. During the birthing process, important bacteria start to colonise the body, including the skin, lungs and gut (Wampach et al., 2018). Researchers have long suspected that this early colonization of bacteria during birth has a pivotal role in determining one’s physical and mental health later in life.

Babies who are born via caesarian section do not appear to acquire some of the microbes from their mothers that are acquired by babies who are born vaginally.

One of the largest studies conducted to date found that depending on whether a baby was born via C-section, or vaginally the bacterial make up was vastly different (Shao et al., 2019).

Babies born by C-section often lack strains of common bacteria typically found in “healthy” individuals – while in contrast, these common bacteria can make up most of the gut community of vaginally delivered babies.

Some of these common bacteria have the ability to stimulate the immune system in early life and some research has suggested this could explain why C-section babies are more prone to develop allergies, chronic inflammatory diseases and metabolic diseases, such as obesity and asthma later in life (Greenhalgh et al., 2016).

Bacteria also have the ability to influence other functions in the body, like the brain. In a study of 201 infants in Australia, there was a clear association between having a reduced number of a common bacteria, Prevotella, in infancy to an increased risk of having emotional or behavioural problems at 2 years of age. Specifically, the children with reduced amounts of this bacteria showed difficulty with socialisation, irritability and coping with stressful situations (Loughman et al., 2020).

Antibiotic exposure

Many women are prescribed antibiotics throughout their pregnancy, several of which have the ability to cross the placenta and expose the foetus to these antibiotics, including Vancomycin, Rifampin and Penicillin VK and Penicillin G (Nahum et al., 2006). Antibiotics are often used during labour in an attempt to prevent complications such as Group B streptococcus colonisation, intra-amniotic infection and prolonged preterm ruptured membranes (Dunn et al., 2017; Ledger, 2006); however, the effects of giving these antibiotics on the diversity and structure of both the maternal and infant microbiomes, is often not considered.

Although the positives of antibiotic usage has dramatically decreased the risk of these complications, it has also increased the emergence of drug-resistant bacteria contained within the microbiome, such as Staphylococcus aureus and Clostridium difficile, in both mothers and newborns (Dunn et al., 2017; Ledger, 2006).

Maternal depression

Depression is a debilitating and life-altering condition that not only affects around 12-22% of pregnant women in New Zealand (Signal et al., 2017), but it also has the ability to cause postpartum complications in 13% of women worldwide (Mutic et al., 2017).

Although there is limited evidence exploring the effects of maternal depression on the infant microbiome, there is some research to suggest that changes within the microbiome of adults is linked to the emergence of depressive-like symptoms. Individuals with major depressive disorders have significantly lower abundance of Bifidobacterium and Lactobacillus, while also lacking overall bacterial diversity (Mutic et al., 2017).

There is even research that has identified that some specific microbes (Coprococcus and Dialister) are completely missing in people who are depressed (Valles-Colomer et al., 2019). Whether this absence is a cause of the depression, or whether these findings could provide insight on a possible treatment has yet to be determined.

We already know that the bacterial composition of mums affects the infant during the delivery process, therefore the lack of diversity within a mother suffering from depression may result in a lack of diverse bacteria available to the infant during the labour and birth process. This then may cause a less diverse infant microbial composition, and possibly increase the risk of health complications later in development. These are all questions we want to explore in the NUTRIMUM trial.

But what does all of this mean?

This area of research is not yet fully understood, so it may be a few more years until we can connect all the dots and be able to make conclusive statements on the connection between the microbiome and mental health, and more specifically how the microbiome might be affecting infant development.

A possible way to describe the connection that the bacteria in our gut may have to our brain is through the hypothalamic pituitary adrenal (HPA) axis, which is a communication network from our brain, to the rest of our body, commonly associated with the human stress response and is activated in times when a person may be experiencing high levels of anxiety.

If this stress response is activated often enough, which is the case in people struggling with anxiety or depression, it can modify the network, to one that is essentially “on edge” all the time and always prepared for stress or anxiety. Certain bacteria found in the gut can affect this communication network by secreting neutrotrasmitters (similar to those that come from our brain, like serotonin and acetlycholine), that mimic a stress response, causing our body to think we are always stressed or anxious.

As we know, gut bacteria are passed from mother to baby. If a mother has high levels of anxiety or depression, it is possible that she has a modified HPA axis,and a gut with neurotranmitter-secreting bacteria mentioned above, which some researchers are suggesting, could be passed on to her baby. This could be a driver behind infant cognitive and behavioural development and could have an impact on their mental health as they progress through their lives.

There are, however, some interesting observations that give us some clues as to what bacterial strains to look at. An amazing study gave babies either probiotics (Lactobacillus rhamnosus) or a placebo, and then followed up thirteen years later to see if any of them had ADHD or autism (Pärtty et al., 2015). ADHD or autism were diagnosed in 17 percent of the children in the placebo group–and none in the probiotic group. That’s a pretty strong effect, and we hope researchers are going to keep on studying this potentially powerful prevention.

Investigating the infant microbiome is an incredibly exciting field of research. Initial research suggests that the bacteria being found in the gut of infants could have a profound impact on later health, including psychiatric illnesses. If this is accurate, there may be a case for attempting to alter the microbiome as early on in life as infancy, and even in utero, therefore possibly changing the way in which infants may develop, including reducing the likelihood of psychiatric illness later in life.

References

Dunn, A. B., Jordan, S., Baker, B. J., & Carlson, N. S. (2017). The maternal infant microbiome: considerations for labor and birthMCN. The American journal of maternal child nursing, 42(6), 318.

Greenhalgh, K., Meyer, K. M., Aagaard, K. M., & Wilmes, P. (2016). The human gut microbiome in health: establishment and resilience of microbiota over a lifetimeEnvironmental microbiology, 18(7), 2103-2116.

Ledger, W. J. (2006). Prophylactic antibiotics in obstetrics–gynecology: a current asset, a future liability? Expert review of anti-infective therapy, 4(6), 957-964.

Loughman, A., Ponsonby, A.-L., O’Hely, M., Symeonides, C., Collier, F., Tang, M. L., Carlin, J., Ranganathan, S., Allen, K., & Pezic, A. (2020). Gut microbiota composition during infancy and subsequent behavioural outcomesEBioMedicine, 52, 102640.

Mutic, A. D., Jordan, S., Edwards, S. M., Ferranti, E. P., Thul, T. A., & Yang, I. (2017). The postpartum maternal and newborn microbiomesMCN. The American journal of maternal child nursing, 42(6), 326.

Nahum, G. G., Uhl, K., & Kennedy, D. L. (2006). Antibiotic use in pregnancy and lactation: what is and is not known about teratogenic and toxic risksObstetrics & Gynecology, 107(5), 1120-1138.

Pärtty, A., Kalliomäki, M., Wacklin, P., Salminen, S., & Isolauri, E. (2015). A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trialPediatric research, 77(6), 823-828.

Shao, Y., Forster, S. C., Tsaliki, E., Vervier, K., Strang, A., Simpson, N., Kumar, N., Stares, M. D., Rodger, A., & Brocklehurst, P. (2019). Stunted microbiota and opportunistic pathogen colonization in caesarean-section birthNature, 574(7776), 117-121.

Signal, T. L., Paine, S.-J., Sweeney, B., Muller, D., Priston, M., Lee, K., Gander, P., & Huthwaite, M. (2017). The prevalence of symptoms of depression and anxiety, and the level of life stress and worry in New Zealand Māori and non-Māori women in late pregnancyAustralian & New Zealand Journal of Psychiatry, 51(2), 168-176.

Valles-Colomer, M., Falony, G., Darzi, Y., Tigchelaar, E. F., Wang, J., Tito, R. Y., Schiweck, C., Kurilshikov, A., Joossens, M., & Wijmenga, C. (2019). The neuroactive potential of the human gut microbiota in quality of life and depressionNature microbiology, 4(4), 623-632.

Wampach, L., Heintz-Buschart, A., Fritz, J. V., Ramiro-Garcia, J., Habier, J., Herold, M., Narayanasamy, S., Kaysen, A., Hogan, A. H., & Bindl, L. (2018). Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potentialNature communications, 9(1), 1-14.

Siobhan Campbell is a Psychology PhD student at Te Kura Mahi ā-Hirikapo | School of Psychology, Speech and Hearing at the University of Canterbury. Her research focuses on the effects of micronutrient supplementation in utero on maternal-infant relationships and infant development. Siobhan is interested in exploring the relationship that micronutrients have on infant gut microbiome, growth and development in addition to how they exert their effects on maternal psychological outcomes post-pregnancy.

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