Topic Overview:

Bacterial communities associated with the human body, particularly in the gut, play critical roles in health and disease. Although available evidence suggests that intestinal bacteria contribute to the pathogenesis of neonatal necrotizing enterocolitis (NEC), the details of this relationship remain poorly understood. This is an important gap in the literature, as NEC remains a major cause of infant mortality. Morowitz uses high-throughput DNA sequencing and proteomics platforms to resolve species- and population-level community succession patterns during the critical period of neonatal gut colonization. Deep whole-genome sequencing of the microbial DNA allows for reconstruction of the genomes of coexisting bacterial, viral, and plasmid populations. In turn, species membership, metabolic potential, and population-level genetic heterogeneity can be tracked over time.

By studying series of samples from more than 200 premature babies, of whom 26 have developed NEC, Morowitz has contributed to a high-resolution understanding of early colonization events in the infant gut. He has demonstrated that features of the preterm gut microbiome include limited microbial diversity, abrupt changes in community membership coinciding with clinical events, preponderance of common nosocomial pathogens in both healthy and diseased individuals, and an overall absence of strict anaerobic species normally present in full-term infants. These genomic studies have provided a critical foundation for ongoing RNA-Seq and mass spectrometry-based proteomics studies to contrast metabolically active pathways among gut bacteria from infants with and without NEC.