Review The Very Low Birth Weight Infant Microbiome and Childhood Health Maureen W. Groer* 1 , Katherine E. Gregory 2,3 , Adetola Louis-Jacques 1 , Shelley Thibeau 4 , and W. Allan Walker 5 This review describes current understandings about the nature of the very low birth weight infant (VLBW) gut microbiome. VLBW infants often experience disruptive pregnancies and births, and prenatal factors can influence the maturity of the gut and immune system, and disturb microbial balance and succession. Many VLBWs experience rapid vaginal or Caesarean births. After birth these infants often have delays in enteral feeding, and many receive little or no mother’s own milk. Furthermore the stressors of neonatal life in the hospital environment, common use of antibiotics, invasive procedures and maternal separation can contribute to dysbiosis. These infants experience gastrointestinal dysfunction, sepsis, transfusions, necrotizing enterocolitis, oxygen toxicity, and other pathophysiological consditions that affect the normal microbiota. The skin is susceptible to dysbiosis, due to its fragility and contact with NICU organisms. Dysbiosis in early life may resolve but little is known about the timing of the development of the signature gut microbiome in VLBWs. Dysbiosis has been associated with a number of physical and behavioral problems, including autism spectrum disorders, allergy and asthma, gastrointestinal disease, obesity, depression, and anxiety. Dysbiosis may be prevented or ameliorated in part by prenatal care, breast milk feeding, skin to skin contact, use of antibiotics only when necessary, and vigilance during infancy and early childhood. Birth Defects Research (Part C) 105:252–264, 2015. V C 2015 Wiley Periodicals, Inc. Key words: preterm infant; microbome; childhood diseases Introduction The very low birth weight (VLBW) preterm infant (<1500 g) infant is thrust from a supportive uterine envi- ronment, in which growth and development proceed in a programmed, staged manner, into a chaotic and toxic extrauterine environment. Without extraordinary means of evaluation and management, many of these infants would not survive. As a result of modern medicine and advanced neonatal technologies, smaller infants are surviving pre- term birth, which provides many new challenges to over- come in both the short and long term. A critical succession of physiological events ensues after birth for both the preterm and term infant, but the adaptations and maturational readiness of these infants are not equivalent, depending upon gestational age, intrauterine and extrau- terine growth, illness, and many other factors. Microbial succession and establishments of microbiota in various bodily niches occurs shortly after birth for both the term and preterm, but the vulnerable and immature preterm faces additional threats and risks related to microbial development. The best characterized microbiome for the preterm infant is that of the gut, but other micro- biomes develop in early life. The skin, for example, while not yet studied extensively in the preterm infant popula- tion, must play an extraordinarily important role in these infants who are born lacking a fully developed epidermis. This review will focus largely on the gut microbiome of the preterm infant, but will also review current knowledge of preterm infant skin microbiology. Studies on human infants are observational, and experimental work with ani- mal models will occasionally be reviewed for mechanistic implications. Part I will review the nature of the preterm infant microbiome, and what is known about the influence of prenatal and postnatal factors on the microbiome early in life. Part II will review potential mechanisms through which childhood diseases might be influenced by the pre- term infant microbiome. Part III will discuss the clinical implications of these discoveries. Part I PRENATAL FACTORS ASSOCIATED WITH THE MICROBIOME While the pioneer gut microbiome of the preterm infant is acquired largely at birth through exposure to vaginal and enteric microorganisms and through breastfeeding, it has recently been confirmed that both term and preterm infants are exposed to microbes during intrauterine life (Steel et al., 2005; Aagaard et al., 2014). The placenta, for 1 Morsani College of Medicine, University of South Florida College of Nursing, Tampa, Florida 2 Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 3 Department of Nursing, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 4 Ochsner Health System, New Orleans, Louisiana 5 Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts Key words: preterm infant; microbome; childhood diseases *Correspondence to: Maureen Wimberly Groer, University of South Florida College of Nursing, Morsani College of Medicine, Tampa, FL. E-mail: mgroer@health.usf.edu Published online 10 December 2015 in Wiley Online Library (wileyonlinelibrary. com). Doi: 10.1002/bdrc.21115 V C 2015 Wiley Periodicals, Inc.