The microbial communities associated with humans, referred to as the human microbiome, provide many important beneficial services to their hosts. Yet, despite their importance, we still know very little about the fundamental processes shaping microbial community formation. Understanding the assembly of microbiomes in newborns following birth is necessary for the design of interventions that manipulate them to improve health and development. Broadly, microbiome assembly is believed to be a product of microbial dispersal and selection by the host, both of which are likely disrupted for newborns in neonatal intensive care units (NICUs). NICUs provide a hygienic environment with relatively limited opportunities for the transmission of commensal microorganisms, and the impact of host selection on resident microbiomes is likely affected by the altered physiology and underdeveloped state of newborns in NICUs. Characterizing the effects of factors that potentially increase the dispersal of commensals, such as skin-to-skin contact care between parents and newborns, or that alter the nature of host selection, such as the development of the immune system, will provide us with a deeper understanding of microbiome assembly in early life. We propose to study the assembly of newborn microbiomes in NICUs, with a focus on the interactive effects of the development of the immune system, skin-to-skin contact care, and microbial dispersal. We will characterize the composition of newborn fecal microbiomes in the NICU using high-throughput 16S rRNA gene and shotgun metagenomic sequencing at multiple time points: just after birth, before and after antibiotic use, and just before transitioning out of the NICU, in addition to regular intervals in between. We will also characterize the immune cell profiles of newborns using mass cytometry on blood samples taken at regular intervals, as well as record the frequency and duration of skin-to-skin contact between parents and infants, and antibiotic use. Using these combined data, we will first determine the relationship between the assembly of newborn microbiomes and the development of the immune system and identify the features that most strongly determine the strength of this relationship. We will then determine the effect of skin-to-skin contact on newborn microbiomes and test the hypothesis that increases in skin-to-skin contact are correlated with increases in microbiome diversity, stability, and the rate of recovery from antibiotics. In addition, we will also test the hypothesis that skin-to-skin contact mediates the relationship between microbiome assembly and immune development. Finally, using ecological theory and dispersal-based community assembly models, we will estimate microbial migration rates and measure the contribution of microbial dispersal to microbiome assembly relative to other factors. By elucidating the ecological mechanisms driving the assembly of newborn microbiomes in NICUs, this research has the potential to inform safe and effective intervention strategies to ensure the transmission and development of healthy microbiomes in newborns.
An important part of postnatal development involves the assembly and succession of an indigenous community of microorganisms, called the microbiome, through a combined process of microbial dispersal and host selection. However, due to a combination of frequent antibiotic use, and limited contact with parents and exposure to their microbiomes, this process may be disrupted for newborns in neonatal intensive care units, which likely has both short- and long-term consequences to newborn health, development, and resistance to infection. We will study how microbial dispersal, the developing immune system, and skin-to-skin contact between parents and newborns interact to shape the assembly of the microbiomes of newborns in neonatal intensive care units.
