The Development of the Gut Microbiome

By Nishant Mehta, Ph.D. candidate

As adults, we have fully matured microbiomes that are constantly interacting with the food we ingest. This conglomeration of hundreds of different bacterial strains works together in synergy to digest food and release byproducts that contribute to our well-being. As humans, we have evolved the capacity to generate new life through an intricate combination of genes from the mother and father. However, these genes only encode for human life, not bacterial life. 

Nothing in our DNA directly translates to bacterial proteins or furthers the reproduction of bacterial life. How then do trillions of bacteria end up colonizing our gut? How does the commensal relationship between microbes and human cells first arise?

How Did Bacteria End Up In Our Gut?

For decades, most of the scientific community agreed that the intrauterine development of the fetus takes place in a sterile environment, free from microbes 2.

 Recent evidence, due in part to the advent of advanced sequencing technology, is challenging this belief. Vestiges of microbes have been found in the fetal amniotic fluid, fetal membranes, and placenta 3. 

In fact, DNA of the common gut bacterial strains Lactobacillus and Bifidobacterium were found in all biopsies of the placenta from C-section births (which circumvent classic exposure to the mother’s native microbes) 4. This evidence suggests that the gut microbiome is undergoing development even before birth.

Mothers and Bacteria Growth

It is hypothesized that the mother can pass gut microbes on to the developing fetus. A randomized patient trial showed evidence that the consumption of probiotics during pregnancy changes the immune signature of cells in the fetal gut and amniotic fluid 5. 

This finding suggests fetal interaction with maternal microbes in the uterus. However, most of the new evidence suggesting microbial colonization in the fetus must be taken with a grain of salt. 

High-throughput sequencing experiments performed on small samples such as fetal biopsies are prone to contamination that can drastically skew results. Even if there is some microbial interaction in utero, the consensus is that the vast majority of gut microbial colonization happens during and immediately following birth.

Newborns and Bacteria Exposure

As a newborn travels through and exits the birth canal, exposure to the vaginal, fecal, and skin microbiota of the mother takes place. First, bacterial species such as Escherichia coli, Staphylococcus, and Streptococcus colonize the infant’s gut. 

These initial species create a local environment devoid of oxygen that allows strictly anaerobic species such as Bacteroides and Bifidobacterium to colonize the gut in the first few days of life 6. 

In addition to direct exposure to maternal and environmental microbiota during birth, microbes are also directly transferred to newborns through breast milk. 

Human breast milk is a direct source of microbes, such as Staphylococcus, Bifidobacterium, and Lactobacillus strains, among many others. Breast milk also contains human milk oligosaccharides (HMOs), which are prebiotics, or molecules that promote the growth of microbial communities 7. 

The infant microbiome is dynamic — it changes from an environment that facilitates breast milk utilization to one dominated by anaerobic organisms that can help digest solid foods. 

By one year of age, the gut microbiome starts to converge on a profile that resembles a fully-formed adult gut 8. This rapid colonization and convergence of microbes emphasize the importance of exposures that take place during birth and in the first year of life.

Disruptions of Neonatal Microbiome

Unfortunately, the natural development of the neonatal microbiome can be disrupted through three common human interventions: C-section delivery, early antibiotic use, and formula feeding. 

Babies that are born through C-section harbor no vaginal microbes initially and are instead first colonized by skin bacteria (e.g. Corynebacterium, Propionibacterium) 9. This delivery method delays the colonization of healthy anaerobic species Bifidobacterium and Bacteroides and increases the levels of pathogenic C. diff bacteria in the gut 10. 

Differences in the bacterial composition of the gut due to mode of delivery are noticeable up to 7 years later 11. Additionally, the use of antibiotics during labor delivery or directly after birth has been associated with a lower abundance of healthy Lactobacillus and Bifidobacterium strains and overall lower diversity of gut bacteria 12. 

Finally, the introduction of formula early in the postnatal period has been shown to perturb the colonization of intestinal microbiota and can increase the prevalence of C. diff while decreasing amounts of Bifidobacterium 13. While the scientific community is still unsure how long-lasting these perturbations can be, we are sure that the immediate changes in microbial composition are quite significant.

If you were born through C-section, were exposed to antibiotics at a young age, or were formula-fed early on, does that mean you are doomed to have an imbalanced microbiome? Not necessarily! 

Although you may have to work a bit harder than those who were born and fed naturally, lifestyle choices as an adult can drastically alter your microbiome. New evidence shows that choosing a plant-based diet vs. an animal-based diet can markedly and reproducibly alter the human gut microbiome 14. 

In mice, exercise has also been shown to drastically shift microbial populations 15. We also know that probiotics are useful for a variety of conditions such as antibiotic-associated diarrhea, H. pylori and C. diff infections, and irritable bowel syndrome 16. 

This evidence suggests that probiotics can significantly shift microbial populations. At Ombre, we aim to be at the forefront of this discovery. We want to better understand how humans can change their own microbiome through the administration of targeted probiotics. By gathering a wealth of microbial sequencing data, we are confident that patterns and correlations will be identified that can improve human health.