The Human Microbiome Project was launched in 2007 by the National Institutes of Health as a strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.1 What has evolved in less than 10 years has been a scientific exploration of the human microbiome that more than tripled. The number of publications relevant to the human microbiome in PubMed has grown from less than 500 in 2011 to more than 1500 in 2014, and, of these, a significant portion has pertained specifically to health and disease during the perinatal and neonatal period. Why has there been such momentum in this field of science and why is early life such an important time to study the microbiome? The answers to these questions are found in this special series of Advances in Neonatal Care.

As emphasized in each of the contributions made to this special series, study of the microbiome is important because human cells are outnumbered by an order of 10 when compared with microbial cells in the human body. We have long known that these microbial cells play a role in health and disease. For example, commensal, or functional and health-promoting intestinal bacteria, has been associated with nutrient absorption and vitamin synthesis, whereas pathogenic bacteria have been associated with inflammatory bowel diseases and sepsis. Although these and other microbial-host relationships were established using culture-based methods for the study of bacteria, the advanced molecular methods used today for study of microbial genomics have shown far more nuanced relationships between the microbial communities populating habitats such as the oral cavity, skin, urogenital and intestinal tracts of the human host. Studies have shown that the influence of the microbiome on health and disease is more complicated than a "one bug-one disease" model.1,2 Rather, the richness (ie, a simple measure of the total number of bacteria present, not accounting for the abundances of the types of bacteria present) and diversity (ie, a quantitative measure of the number of different types of bacteria, as well as how these types are distributed across the data set) of the microbiome in a specific human habitat appear to drive disposition toward health or disease state. Further unraveling these relationships will result in both an improved understanding of how the microbiome influences health and the pathogenesis of disease. With this knowledge we will be more ideally prepared to manipulate the microbiome for intervention purposes.

Manipulation of the microbiome is likely to have very promising therapeutic capabilities when we consider the relationships between microbial colonization, development of the immune system, and inflammatory disease. Studies have shown that exposure to commensal microbes early in life is associated with the development of a healthy immune system and appropriate inflammatory responses. This occurs as a result of crosstalk between the intestinal microbiota and gut epithelial cells through pattern-recognition receptors, 1 of which are toll-like receptors (TLRs) located on the epithelial cell surface.3,4 Toll-like receptors are expressed as early as 18 weeks of gestation and continue to be utilized by microbes as a way to communicate with host cells well into adulthood.3,4 This microbial interaction with TLRs results in the activation of epithelial cell genetic material, which triggers the production of cytokines responsible for initiating an inflammatory response to injury, stress, or harmful pathogens. Thus, the innate crosstalk between microbes and cells through TLRs impacts the maturation of many features of the immune system including immunosensory cells and cytokines, resulting in a protective effect and reduction in cellular injury and inflammation.3,4 These and other complex mechanisms help explain the relationships between microbes, immunity, and inflammation and underpin why achieving a more optimal microbiome may mitigate the inflammation associated with many diseases.

Exploration of the microbiome for the reasons outlined above is important for populations across the life span. However, because the initial acquisition of the microbiome that occurs at birth and during infancy has been shown to influence both short- and long-term health outcomes, study of the clinical factors that influence this acquisition is important.5 The major drivers of the acquisition process have been shown to be mode of birth,6,7 antibiotic and other medication administrations,8-10 nutrition,5,11 and environmental exposures in the hospital setting.12 The culmination of this research has shown that infants who are born via the vaginal canal, not exposed to antibiotics or other medications such as H2 blockers, and fed breast milk, have a microbiome that is rich in lactobacillus (likely from the maternal vaginal canal) and bifidobacteria (likely from feeding with breast milk). Both of these types of bacteria are commensal in nature and important to more normal processes.

In this special series, a collection of 4 articles focuses on specific aspects of the microbiome in neonatal health. Dr Cong and colleagues13 highlight the evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. In addition, this article discusses the role of the gut microbiome in modulating stress and pain responses in high-risk infants. In the article published by Hartz et al,14 a systematic review focused on potential neonatal intensive care unit environmental influences on the infants' microbiome was conducted. This work yielded the identification of factors that have been shown to impact the infants' microbiome-parental skin, feeding type, environmental surfaces, caregiving equipment, healthcare provider skin, and antibiotic use. Clinical strategies for balancing the influence of these factors on the infants' microbiome are suggested. The contribution submitted by Dr Dunlop and colleagues15 pertains to the maternal microbiome and pregnancy outcomes that impact infant health. This review provides a summary of the role of the maternal microbiome in pregnancy outcomes known to adversely influence infant health, including preterm birth, cardiometabolic complications of pregnancy such as preeclampsia and gestational diabetes, and excessive gestational weight gain. Furthermore, it reviews factors with an established link to adverse pregnancy outcomes that are known to influence the composition of the maternal microbiome and suggests some initial strategies for promoting a healthy maternal microbiome. Finally, Dr Gregory and her team present data on intestinal colonization of the preterm infant with Bacteroides, 1 specific type of bacteria that is an important member of the intestinal microbiome, which she has shown is influenced by mode of birth.

Further unraveling the microbiome holds great promise for patients and families across the life span. This work will be especially exciting to those who care for infants and their families early in life, where the therapeutic potential associated with the microbiome is likely to have a great impact on both short- and long-term health outcomes. I applaud the editors of Advances in Neonatal Care for dedicating this special series to the topic of the human microbiome, and I hope that the readership finds this collection of articles interesting, educational, and relevant to the care you provide to infants and their families.

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