In 2007, the Human Microbiome project began and was funded by the National Institutes of Health. Once the human genome project was completed, work continued to identify the microbiome or bacterial colonization of the human body. It is now recognized that the microbiome plays an important part in health and well-being. This microbiome interacts with both genetic and environmental factors which effect health outcomes.1 It has been discovered that cells in the microbiome outnumber human cells by an order of 10.2 The extent of the influence and interaction between this bacterial colonization and health or illness is just beginning to be understood. While many studies have found the presence or absence of specific bacteria in association with a disease, how and when to influence this for benefit is not yet understood. Particularly, what the “normal” microbiome of a preterm infant actually is should be identified. This would help target treatments concerning the microbiome for this population.
It is now believed that the preterm infant’s intestines are colonized before birth, contrary to what we used to think about this colonization happening entirely after birth.2-4 It also turns out that the mother’s own microbiome, and other factors, influence this initial colonization. The mother’s microbiome influences risk for preterm birth as well as risk for gestational diabetes and pre-eclampsia.5 This colonization of the neonatal gut is influenced by mode of delivery and important for many reasons, including immune development and avoidance of bacterial overgrowth. The colonization of Bacteroides is earlier and with higher levels in infants born vaginally versus those born via cesarean section. Cesarean section has also been shown to result in lower colonization with Lactobacillus and Bifidobacterium. These beneficial bacteria are referred to as commensal bacteria and bacteria that commonly lead to disease are referred to as pathogenic bacteria. Important to the microbiome are both the number and diversity of bacteria. While beneficial in the gut, they may cause infection if outside the gut. Chronic stress and pain such as that experienced by some NICU patients can lead to translocation of this bacteria from the gut into the bloodstream, leading to infection.6
Further development of this microbiome is influenced by parental and healthcare provider skin, antibiotic use, diet (breast milk versus formula) and environmental surfaces/area.7, 8 The bacteria will be decreased when antibiotics are used. It is not clearly understood how much this effect is influenced by short-term exposure to antibiotics such as a 2-day rule out course as compared to a longer course as no prospective trials have been done. One case report analyzed the stool of twins who were treated with antibiotics. One twin regained previous colonization and the other twin developed necrotizing enterocolitis and received subsequent antibiotic treatment.9 It is also important to note that it is not only antibiotics administered to the infant that effect intestinal colonization but also antibiotics administered to the mother before delivery.10
The intestinal microbiome has received a lot of attention because of how this may influence the risk of necrotizing enterocolitis. However, other microbiomes being studied are those of the skin, bladder, mouth and vagina. The intestinal microbiome is also important because alterations or imbalances have been linked with many acute and chronic health conditions such as overall immune development, inflammatory bowel disease, obesity and cardiovascular disease.1
While, as yet, there is not much known about how we can safely enhance the microbiome, some measures that can be used to protect its development are to promote breast feeding, encourage frequent and early skin to skin contact between parents and infants and appropriate use and selection of antibiotics. It has been well-recognized that infants receiving breast milk have improved immunity. This is not only due to the immunoglobulin, IgA, passed on to the infant but also to the beneficial bacteria that help colonize the intestines, aiding in immune development. Perhaps there is an advantage to direct breast feeding where skin to skin contact is combined with the delivery of breast milk. This is necessarily delayed in preterm infants but could often be implemented sooner than it is. It is not yet known if the same advantage in development of the intestinal microbiome occurs when donor milk is given rather than mother’s own milk. But, while there are some common bacteria that are recognized as being protective, each woman develops a more diverse microbiome one from another and over time during the pregnancy.5
Further discussion about microbiome development centers around environmental influences, including hand washing of staff and parents, cleaning of the infant’s area, changing of incubators, suctioning and oral care practices, including feeding tube use.8 This influence will be unique for the infant in the NICU for days, weeks or months. This not only exposes them to different bacteria in the environment but also separates them from their mother who would normally provide commensal bacteria.
The literature in this area has increased dramatically in the last 5 years and the research continues to develop. It also highlights the lack of knowledge as new discoveries are made. In many ways, it serves to reinforce what we already know is best practice, like keeping mother and baby together as much as possible, encouraging breast feeding and antibiotic stewardship. It also informs us that keeping the infant in a near sterile environment is not really the best. However, we don’t know much about how we should artificially manipulate bacteria by administering it to the infant to aid in proper development of a commensal microbiome. Watch your professional journals for breaking news in this area.
Looking for more on this topic? Read
The Human Milk Dynamic Duo: Bacteria and Sugar
- Cong, X., Henderson, W. A., Graf, J., & McGrath, J. M. (2015). Early Life Experience and Gut Microbiome: The Brain-Gut-Microbiota Signaling System. Advances in Neonatal Care, 15(5), 314-323.
- Gregory, K.E. (2015). Guest Editorial: Unraveling the Microbiome. Advances in Neonatal Care, 15(5),312-313.
- La Rosa, P. S., Warner, B. B., Zhou, Y., Weinstock, G. M., Sodergren, E., Hall-Moore, C. M., … & Hoffmann, J. A. (2014). Patterned progression of bacterial populations in the premature infant gut. Proceedings of the National Academy of Sciences, 111(34), 12522-12527.
- Koenig, J. E., Spor, A., Scalfone, N., Fricker, A. D., Stombaugh, J., Knight, R., … & Ley, R. E. (2011). Succession of microbial consortia in the developing infant gut microbiome. Proceedings of the National Academy of Sciences, 108(Supplement 1), 4578-4585.
- Dunlop, A. L., Mulle, J. G., Ferranti, E. P., Edwards, S., Dunn, A. B., & Corwin, E. J. (2015). The Maternal Microbiome and Pregnancy Outcomes that Impact Infant Health: A Review. Advances in neonatal care: official journal of the National Association of Neonatal Nurses, 15(6), 377.
- Cryan, J. F., & Dinan, T. G. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature reviews neuroscience, 13(10), 701-712.
- Gregory, K. E., LaPlante, R. D., Shan, G., Kumar, D. V., & Gregas, M. (2015). Mode of Birth Influences Preterm Infant Intestinal Colonization With Bacteroides Over the Early Neonatal Period. Advances in Neonatal Care, 15(6), 386-393.
- Hartz, L. E., Bradshaw, W., & Brandon, D. H. (2015). Potential NICU Environmental Influences on the Neonate’s Microbiome: A Systematic Review. Advances in Neonatal Care, 15(5), 324-335.
- Stewart, C. J., Marrs, E. C., Nelson, A., Lanyon, C., Perry, J. D., Embleton, N. D., … & Berrington, J. E. (2013). Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis. PloS one, 8(8), e73465.
- Arboleya, S., Binetti, A., Salazar, N., Fernández, N., Solís, G., Hernández-Barranco, A., … & Gueimonde, M. (2012). Establishment and development of intestinal microbiota in preterm neonates. FEMS microbiology ecology, 79(3), 763-772.