The microbial composition of the gut likely contributes to a wide-range of health and disease states including intestinal inflammation, atopic disease, and possibly diseases of adulthood, such as heart disease and obesity. The early establishment of the gut microflora is suspected to have a particularly profound impact protecting the gut from infectious disease and on long-term subsequent health by predisposing individuals to atopic or autoimmune disease later in life. In contrast to the large-scale efforts of the Human Microbiome Project to characterize the microbial flora of healthy adults, relatively little has been accomplished to characterize the early establishment of the microbiota in infants.

The administration of antibiotics to infants has the capacity to profoundly affect the early acquisition, establishment, and natural maturation of commensal microflora. Prematurity is another major factor that is thought to influence “normal” gut microbial composition in early life. A high number of pre-term infants receive antibiotic therapy prophylactically; the immediate and long-term effects of antibiotic treatment on infant and later health outcomes are unknown. We hypothesize that gestational age influences the ability to support “normal” gut microbiota, and that antibiotic administration in the first few weeks of life can alter or delay the development of a “normal” microbiota and may lead to adverse health outcomes. If we hope to promote the healthy establishment of early gut colonization and thereby improve health outcomes, we need to establish what “normal” colonization looks like across gestational ages and apply this knowledge as a benchmark to understand the impact of antibiotic treatment in early postnatal life.

The environment of the neonatal intensive care unit (NICU) and the frequent use of antibiotics are thought to contribute to aberrant gut colonization, which in turn is thought to contribute to risk of enteric diseases. In this project, we will establish the interrelationships between gestational age, antibiotic usage, development of the gut microflora and enteric disease. We will examine the microbiome of four gestational age cohorts ranging from extremely preterm to term, from the first postnatal week to 18 months of age, and will include untreated as well as and antibiotic-treated infants.

This sequencing project was supported by the National Institute of Allergy and Infectious Disease, National Institutes of Health funded Genome Sequencing Center for Infectious Diseases at the Broad Institute.