The Development of the Infant Intestinal Microbiome: An In-depth Exploration from a Pediatrician’s Viewpoint

Children are and always will be a marker of a society’s quality and focus on their health. When we look at the landscape of childhood health trajectories, we see a declination in quality and an inclination toward diseases of immune dysregulation and underlying chronic unchecked inflammation. What is the genesis point, or where is ground zero? 

For me, that answer is the newly understood ecosystem called the intestinal infantile microbiome.

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What is the Intestinal Microbiome?

The intestinal microbiome is a complex and dynamic community of microorganisms that plays a crucial role in all mammalian health, particularly in the early stages of life. The development of the human infant intestinal microbiome has profound implications for the child's immune system, tolerance to the outside world, metabolism, and health trajectory. 

Understanding the factors that influence the establishment and evolution of this microbiome can help in devising strategies to promote optimal health from infancy through adulthood. This article dives deep into the key aspects of the development of the infant intestinal microbiome, highlighting the critical stages, influencing factors, and long-term health implications.

How Do Infants Establish Their Gut Microbiome?

The infant gut is initially believed to be sterile or nearly sterile at birth. The colonization process begins during delivery, with the mode of birth being a significant determinant of the initial microbiome composition. Mode of delivery is important primarily because it is by the maternal microbiome, which is defined as the community of organisms that inhabit a woman's mucosal gastrointestinal tract and vagina, that the infant obtains microbes to establish his or her ecosystem within the GI tract. 

The resident maternally transferred organisms are bacteria, fungi, archaea, and viruses. These opportunistic players are not merely freeloaders but actually, symbiotically affect us in ways previously thought impossible. 

Stated best here: "We hypothesize that an appropriate microbiota is essential for healthy early development, pregnancy maintenance, and the first years of childhood." (Nuriel Ohayon et al. 2016) 

Vaginally delivered infants are exposed to their mother’s vaginal and fecal microbiota, predominantly acquiring species such as Lactobacillus and Bifidobacterium. In contrast, infants delivered via cesarean section are more likely to be colonized by skin-associated and environmental bacteria, including Staphylococcus and Corynebacterium (Dominguez-Bello et al., 2010). 

This has been a trending change since the 1970s when C sections were 5.5%. They are now about 32% of births. (Placek et. al. 1980)(Osterman M. 2022) Fundamentally, we are now in a new realm of ecosystem dynamics that are massively dissimilar to millions of years of humanity.

How is the Maternal Microbiome Established?

First, we must look back at how the maternal microbiome is established. Here are two competing modern types, and many mothers fall somewhere in between the 2 patterns.

Pattern One - This pattern tends to be associated with better overall health.

The microbiome for Mom was established at her birth with her passage through the vaginal canal and her subsequent exposure to the vaginal and rectal bacterial flora of her mother. Then, Mom further upgrades her microbiome by latching onto the breast to feed. 

Breastmilk is the perfect food source for her bacteria as it is made up of 8% non-digestible sugars. Babies lack enzymes to break down these sugars, leaving them for the bacteria to have a party with. Over the next few years, Mom's gut microbes will be shifted and established by the food that she eats, medicines and chemicals that she is exposed to, stress events, and much more. 

Or

Pattern Two - This pattern tends to have less favorable health outcomes.

The microbiome for Mom was established at birth through a caesarian section, where her initial exposure was to the skin and gloves of the medical team. There are many  reasons why a c-section might be necessary. However, the downside is that the baby does not get that initial exposure to the vaginal microbiome.

There are also many reasons for some mothers to choose or require formula feeding. This means that for some infants, formula feeding may follow a c-section, which, unlike breast milk, is not the perfect food source for her bacteria as it is not made up of 8% non-digestible sugars and is not dynamic over time.

Over the next few years, Mom's gut microbes will be shifted and established by the food that she eats, medicines and chemicals that she is exposed to, stress events, and much more. (Pollan M. 2013)

Now that Mom's microbiome has been established, she becomes the primary influencer for her baby's microbiome. This process repeats itself through the generations from mother to child. (Dunlop et. al. 2015) 

What Else Influences The Microbiome?

If Mom's microbiome is the main player in starting her baby on the right track, what else influences her microbiome? It is roughly the same as what will influence the infants post birth and after breastfeeding, therefore, let us look there instead of repeating both upstream understandings. 

The most critical long-term aspect shaping the gut microbiome over time after it is established at birth is the primary influence of diet.

The type of feeding is a critical factor influencing the composition of the infant gut microbiome. Breast milk provides not only essential nutrients but also a variety of bioactive compounds, including human milk oligosaccharides (HMOs), which selectively promote the growth of beneficial bacteria such as Bifidobacterium. These bacteria play a key role in metabolizing HMOs, producing short-chain fatty acids (SCFAs) that are beneficial for gut health and development by providing a metabolic substrate for intestinal epithelial growth and repair. (Bode, 2012) 

Formula-fed infants, on the other hand, tend to have a more diverse microbiome with higher levels of Clostridium and Enterobacteriaceae, which can lead to different metabolic and immune outcomes. (Penders et al., 2006) Microbial diversity is a key to an aging microbiome. However, early on, this is not characteristic throughout history. 

Beyond the mode of delivery and feeding practices, several environmental and genetic factors influence the development of the infant microbiome. A key and unexpected net negative is the development and overuse of antibiotics, either directly to the infant or indirectly through the mother during pregnancy or breastfeeding. The perinatal and early infancy use can significantly disrupt the microbiome, often leading to a decrease in bacterial diversity, but more importantly the loss of beneficial species. (Azad et al., 2014) 

Additionally, the infant’s genetic makeup can affect the immune system's interaction with the microbiota, influencing the composition and stability of the gut microbiome. (Goodrich et al., 2014)

The Stages of Infant Intestinal Microbiome Development

The development of the infant intestinal microbiome can be broadly divided into three stages: the initial colonization phase (birth to 1 month), the transitional phase (1 to 6 months), and the stable phase (6 months to 3 years). 

Initial Colonization Phase

During the first month of life, the infant gut microbiome is relatively simple and is characterized by low diversity. As stated, the initial bacterial populations are primarily influenced by the mode of delivery and the immediate environment. Facultative anaerobes such as Escherichia coli and Streptococcus are among the first colonizers, creating an anaerobic environment that allows obligate anaerobes like Bacteroides and Bifidobacterium to establish which is the precursor to older age microbial compositions. (Matamoros et al., 2013)

Transitional Phase

Between 1 and 6 months, the infant gut microbiome undergoes significant changes, influenced largely by the introduction of solid foods and continued breastfeeding or formula feeding. This period is marked by an increase in microbial diversity and the establishment of a more complex and stable microbiome. The introduction of solid foods, in particular, leads to an increase in bacteria involved in the digestion of complex carbohydrates, such as Firmicutes and Bacteroidetes. (Koenig et al., 2011) 

The complex carbohydrate foods are filled with non-digestible fibers for the baby that are especially necessary for the over 200 different enzymes produced by Bifidobacter infantis in the microbial metabolism consumption process. 

This is symbiosis 101. We drink Mom’s milk. That milk feeds the bacteria, who in turn release short-chain fatty acid metabolites that feed the babe’s intestinal cells, developing a healthy gut for the bacteria to thrive in. There is an ever-growing body of evidence that the standard American highly processed diet is a change agent negatively for intestinal microbial solvency and diversity.

Stable Phase

By the age of 3 years, the microbiome of the child resembles that of an adult, with a stable and diverse community of microorganisms. The composition at this stage is influenced by a variety of factors, including diet, environment, and genetics. The stable microbiome plays a crucial role in maintaining gut health, protecting against pathogens, and, most importantly, modulating the immune system. (Yatsunenko et al., 2012) 

Healthy Infant Microbiome and Long-Term Health

This last fact is a whole other article in itself. Microbially induced immune solvency must develop in a tolerant pattern and be primed for pathogen control and inflammation resolution for long-term health to be disease-free. There is significant evidence now that abnormal infantile microbiomes affect drug metabolism, vaccine responses, and nutritional metabolism. 

Thus, the establishment of a healthy microbiome in infancy is critical for long-term health. An imbalance in the early microbiome, known as dysbiosis, has been associated with a variety of health conditions, including allergies, asthma, obesity, and autoimmune diseases. 

For example, studies have shown that infants with a less diverse gut microbiome are at a higher risk of developing allergies and asthma later in childhood (Arrieta et al., 2015). 

Similarly, early antibiotic exposure, which can disrupt the microbiome, has been linked to an increased risk of obesity and metabolic disorders (Bailey et al., 2014). The impressive work of Dr. Patrice Cani has helped us understand that dysbiosis will lead to a state of low level systemic metabolic endotoxemia leaving humans inflamed and at risk for the four horsemen of the diseases of aging: cardiovascular disease, hypertension, diabetes, and cancer. 

Research-Driven Perspectives

Let us look at recent literature to expand this understanding further before giving them to-do guidance: 

1) In a study presented at the Pediatric Academy of Sciences meeting this year, Dr. Rautava from the University of Turku analyzed the intestinal microbes of 36 infants that were either born at term or late preterm. His findings are disturbing for the average pediatrician and new parent. What he found was that even 2 days of antibiotic exposure in a neonate for a concern of infection caused the gut bacteria to shift in a negative way. 

There was an increase in unhealthy Clostridial species and a decrease in beneficial Bifidobacter and Bacteroides species at 1 and 6 months of age. These bacterial shifts are associated with allergies, asthma, obesity and inflammatory bowel disease. 

This puts us in a pinch. We don't want to treat a child with antibiotics because of the negative effects, but at the same time, we have to be careful not to miss a real bacterial blood infection that could kill the child. What a quandary!

2) In another study presented at the Pediatric Academy of Sciences meeting this year, Dr. Dawson-Hahn presented data on early antibiotic exposure and obesity risk in almost 5000 children. The results as presented showed that children exposed to antibiotics prior to 2 years of age had a significantly increased risk of obesity. 

For every treatment course, the child had a 3% increased risk of obesity by the age of 5 years. The average child in the study received 4 courses of antibiotics. They further looked at the timing of antibiotic exposure and noted the bulk of the obesity risk was associated with antibiotic use before 12 months of age. 

The timing effect adds more data to the fact that the developing microbiome of infancy is most at risk for alterations that cause disease. We need to be very careful when we weigh the risks and benefits of antibiotic use in the early years of a child's life.

3) We have long known that fiber is incredibly important for the human intestinal microbiome, which is critical for immune tolerance and immune solvency. "Animal studies have shown that maternal low-fiber diets during pregnancy may impair brain development and function in offspring, but this has not been validated by epidemiological studies."

In a study published in Frontiers in Nutrition, we see an analysis of 76,000 mother-child dyads using data from the Japan Environment and Children's Study. Maternal dietary fiber intake was classified into quintiles of intake and then crossed against developmental norms. 

Developmental delay was assessed in five domains: 1) communication, 2) gross motor, 3) fine motor, 4) problem-solving, 5) and personal-social skills at the age of 3 years. 

"Results: The lowest intake group of total dietary fiber had a higher risk of delayed communication with an odds ratio of 1.5, fine motor (OR1.45), problem-solving (OR1.46), and personal-social skills (OR1.30) than did the highest intake group. An analysis that excluded the effects of insufficient folic acid intake during pregnancy also showed a similar trend." (Miyake et. al. 2023)

This study showed that maternal dietary fiber deficiency during pregnancy might influence an increased risk of neurodevelopmental delay in offspring. 

If children’s outcomes are a marker of a society’s quality, then the focus on their health must be of paramount importance. Thus, we have just learned about levers that can be pulled on to alter a child’s trajectory permanently and in turn a society, if the levers are pulled on at a large scale. 

Lab Testing for the Infant Microbiome

When looking for a lab test to ascertain microbial makeup in newborns, you have few options, and validity remains a concern. 

• The Baby Gut Test by Tiny Health is the newest microbiome test on the market for younglings. 
• The GI Effects stool profile by Genova Diagnostics and The GI-MAP from Diagnostic Solutions have age ranges north of 2 years old. 

Fundamentally, I lean on the principles as stated above unless I am concerned about a specific case warranting further newborn testing.

5 Strategies for Promoting a Healthy Microbiome in Infancy

Given the importance of the early microbiome in shaping long-term health, several strategies have been proposed to promote a healthy microbiome in infants. These include:

1. Encouraging Vaginal Delivery:

When possible, vaginal delivery should be encouraged to facilitate the natural transfer of maternal microbiota to the infant. Talk to your obstetrician of vaginal transfers if your child will or does arrive via c section. 

2. Breastfeeding:

Exclusive breastfeeding for the first six months of life is recommended, as breast milk contains essential nutrients and bioactive compounds that promote the growth of beneficial bacteria.

3. Minimizing Antibiotic Use:

Antibiotic use should be limited to absolutely necessary cases to prevent the disruption of the developing microbiome. When antibiotics are required, probiotics may be used to help restore microbial balance.

4. Introduction of Solid Foods:

The introduction of a diverse range of solid foods, including fiber-rich fruits and vegetables, will promote the growth of a diverse and stable microbiome. Begin first foods at 4 months of age with vegetable matter.

5. Probiotics and Prebiotics:

Supplementation with probiotics (live beneficial bacteria) and prebiotics (compounds that promote the growth of beneficial bacteria) may help support the development of a healthy microbiome, particularly in infants at risk of dysbiosis. Consider Bifidobacter subspecies infantis as well as Lactobacillus rhamnosus when approaching this supplement. 

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Key Takeaways

• Infant Microbiome Development: The intestinal microbiome of infants is initially influenced by the mode of delivery, with vaginal births promoting a beneficial microbiome compared to cesarean sections.
• Maternal Microbiome Influence: The mother's microbiome, established during her own birth and influenced by her diet and environment, plays a crucial role in shaping her baby's microbiome.
• Diet's Critical Role: Breastfeeding supports a healthy microbiome through nutrients and bioactive compounds, while formula feeding can lead to different microbial outcomes.
• Impact of Antibiotics: Early antibiotic exposure disrupts the microbiome, increasing the risk of allergies, asthma, obesity, and inflammatory diseases.
• Importance of Fiber: Maternal fiber intake during pregnancy is linked to the neurodevelopmental health of the child, emphasizing the need for a high-fiber diet.
• Long-term Health: A healthy early microbiome is vital for immune development, metabolic health, and long-term disease prevention.
• Strategies for Health: Promoting vaginal delivery, exclusive breastfeeding, careful antibiotic use, early introduction of diverse solid foods, and considering probiotics/prebiotics are recommended for a healthy infant microbiome.