The Development of the Gut Microbiome in Young Children

Introduction to the Gut Microbiome

The gut microbiome is composed of trillions of microbes that form a protective barrier in the digestive system of humans as well as many other organisms. The gut microbiome, also known as gut flora or gut microbiota, is a part of the innate immune system that is essential for human health. The gut microbiome protects humans from pathogenic microbes and helps regulate the uptake of several important vitamins and other nutrients. Within this microbiome, there is an immense level of diversity of species. The majority of these species are bacteria, but various fungi and archaea have also been identified (1).

Because the gut microbiota is such an important mechanism of defense in humans, it begins developing as soon as a baby is born. While the majority of bacterial infiltration into the gut occurs just after birth, an initial exposure to beneficial microbes takes place in the placenta in utero (6). It has been found that the gut flora of infants develops for about 3 years to reach maturity (1)(3)(4)(12)(9).

There are a variety of different factors that can alter the composition of the gut microbiome, including age, geography, diet, weight, and genetics. In children, maternal genes and health as well as diet and environment play a large role in the development and change of the microbiota. Research has been done to show the effects of cesarean section, natural birth, breast feeding, and formula feeding on the neonatal microbiome. A healthy gut microbiome makes important contributions to human health and the regulation of metabolism (1)(8)(12).

Electron micrograph of the Ebola Zaire virus. This was the first photo ever taken of the virus, on 10/13/1976. By Dr. F.A. Murphy, now at U.C. Davis, then at the CDC.

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What Factors Influence the Composition of the Gut Microbiome?

Diet has been found to be one of the largest influencers of the composition of the gut microbiome. Not only does food provide the nutrients necessary to support a robust microbiome, but the microbes that are contained in the food also contribute to the diversity of the microbiome. An unhealthy diet often degrades the microbial diversity of the gut, which leaves the affected person more susceptible to inflammation and infection (8)(12)(1). Differing diets require the expression of different genes because some foods must be broken down in unique ways. Unhealthy and unbalanced diets, such as ones that are high in sugar and fats, negatively affect the microbiome because of a lack of sustainable nutrients and lead to an increased risk of illness, diabetes, and inflammatory bowel disease (IBD). Malnourishment also results in a lack of proper nutrients to sustain a healthy and balanced microbial community in the gut (8). Processed foods, those that are high in calories, sugar, and fats, and lack fibers and important vitamins, degrade the gut flora and lead to increased chances of illness (12). Because diet is so influential in the configuration of the gut microbiome, any factors that affect diet come into play as well when discussing gut microbiota. Geography influences the genetics of a person and their access to different types of nutrients, which in turn alter the diversity of the microbiome. The regulation and expression of certain genes can lead to a more suitable environment for colonizing bacteria or can allow for the efficient breakdown of different compounds, which improves the conditions for the gut flora. Conversely, the suppression of a gene has the potential to create a disruptive environment for the gut flora (12). The same factors that alter the composition of the gut microbiome in adults also influence the contents of breast milk (2).

Prebiotics induce the growth of beneficial microbes, and probiotics are the helpful bacteria that promote a robust gut microbiome. Prebiotics allow the bacteria to thrive and diversify by providing nutrients.

The Gut Microbiome in Infants

The gut microbiome performs several necessary functions that sustain and enrich human life. The microbes that inhabit the gastrointestinal tract aide in absorbance and utilization of nutrients. While children are not born with an inherently mature gut microbiome, the system develops overtime as their lifestyle changes (9).

Immediately after birth, babies experience an influx of bacterial exposure, both from their mother and their surroundings (1)(3)(5)(6)(9). This initial “vaccination” from the mother’s vaginal flora sets the foundation for a healthy gut microbiome (3)(5)(9). As children grow up and develop, their gut microbiome does as well because it is colonized by more diverse microbes. It is widely accepted that the gut microbiome of young children matures towards the composition of the microbiome of adults within the first three years of life (1)(4)(3)(12). While adults with similar lifestyles and geographical areas are more uniform in the composition of their gut microbiome, children have increased levels of variability between them (12).

In the gut microbiomes of infants that are 1 to 10 days old, the bacteria Enterococcus and Streptococcus are the most prevalent (4). After this initial period, the microbiome of children, especially those who are breastfed, is dominated by Bifidobacterium (4)(11). 4 months into an infant’s life, the circadian rhythm begins to develop, due to the production of melatonin. After the first year of life, the microbiome of children resembles the microbiome of the mother and is more functional and complicated. During breastfeeding, when milk is the main component of a child’s diet, lactose metabolism produces energy. As infants are weaned off of breast milk, which usually occurs after the first year in mothers who breastfeed, the gut flora develops more diverse metabolic pathways. These include the breakdown of carbohydrates, complex sugars, and starches, as well as fermentation and the synthesis of various nutrients and vitamins (11).

While the microbiome of an infant is developing, it is particularly susceptible to the effects of antibiotics. Several species of bacteria contain or develop antibiotic resistance genes naturally. However, when antibiotics are introduced to the microbiome of children, they become more susceptible to invasion by pathogens, inflammation, and infection. Antibiotics also lower the diversity of the gut microbiome of children.

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Cesarean Section and Natural Birth

Vaginal Birth Vaginal birth provides a newborn baby with an initial exposure to the flora of the mother, which in turn helps the gut microbiome develop and diversify. This initial bacterial colonization is extremely important in the foundation of a healthy gut microbiome. Vaginal delivery allows for the microbes of the mother as well as the bacteria of the surroundings to enter the gut of the newborn child. Because the first substantial exposure to microbes comes from the mother’s bacteria, the child’s microbiome resembles the mother’s for around 6 months to a year, until the baby’s own microbiome begins to fully develop and mature (3)(5)(9)(11).

The placenta has a concentration of bacteria of the Escherichia genus, which does not differ for vaginal birth and C-section, but may differ slightly between women. There are significant differences in the bacteria that inhabit the microbiome in babies born naturally versus those delivered by C-section. For children born by vaginal delivery, Bifidobacterium, Parabacteroides, and some Bacteroides are present in the gut. Comparatively, the microbiome of a C-section baby includes Enterobacter, Haemophilus, Streptococcus, and other skin and oral bacteria. Vaginal birth leads to a slightly more developed microbiome that has loose resemblance to that of an adult (11).

Most of the initial bacterial colonizers of the microbiome, which are mostly from the mother, decrease in number overtime. Certain maternal strains of bacteria influence the long term health of the child and his or her microbiome. Because the mother’s microbes are the first to colonize the child’s GI tract, they are more likely to adapt and successfully establish themselves in the child’s gut microbiome than the bacteria from other sources. Selective pressures and environmental selection result in the maturation of the child’s microbiome as they grow older (9). Cesarean Section A cesarean section, also known as a C-section or Cesarean Delivery (CD) is a surgical procedure in which the abdomen of a pregnant woman is cut open to remove the child. This procedure can be done in emergency situations, or it can be voluntary. Because the child does not move through the birth canal, there is no initial exposure to the vaginal flora of the mother and the child’s gut microbiota do not closely resemble that of the mother. Instead, there is an increased proportion of bacteria from the surroundings, including the others present in the room and the room itself. Often, a mother’s microbes are able to adapt to the system of the child better than other microbes, but the lack of vertical transfer of bacteria from the mother to the child means there is increased range and diversity of bacteria from the surroundings that initially colonizes the intestines. However, there is evidence of a delay in the establishment of the gut flora in babies delivered by C-section. This delay can last up to six months, which endangers the balance and establishment of healthy gut microbiota (1)(5)(11).

Although the diversity of bacteria in the gut of children born by C-section is initially higher, the delay in colonization leads to an eventual decrease in diversity, which weakens the microbiome and its response to pathogens (1). While some species of bacteria are able to colonize the gut microbiome of a child delivered by C-section quickly, they often are not able to adapt to the environment or establish themselves in a sustainable manner. This hindrance to colonization can leave these children more vulnerable to infection, inflammation, or other diseases usually prevented by a healthy gut. It has been hypothesized that the anesthesia and other drugs given to a mother during a C-section may have an effect on the bacterial colonization rates in infants, but more research still needs to be done to provide evidence for this idea (5).

Because C-sections do not involve the hormones and chemical signals that are necessary for the induction of labor and vaginal birth, the procedure can also affect the production or composition of breast milk. The changes in milk production due to the lack of hormonal signals can include a decrease of human milk oligosaccharides (HMOs), which are beneficial to the human gut (2).

The genetics of obesity are often inherited by children, leading to an increased risk of this condition in childhood. Mothers who are obese or overweight often have C-sections, particularly emergency ones. Because of the disturbances a C-section has on a balanced and developed gut microbiome in infants, the likelihood of a child becoming overweight in their first few years of life is increased. The combination of these two factors—obesity genetics and changes in microbial composition in the gut—lead to increased rates of childhood obesity in the children of overweight mothers who underwent emergency C-sections (7).

Breast Milk and Formula Milk

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Edited by Sophia Knaysi, student of Joan Slonczewski for BIOL 116 Information in Living Systems, 2020, Kenyon College.