PURPOSE OF REVIEW: In newborns, interactions between the host and the microbiome operate synergistically, modulating host immune function and shaping the microbiome. Next generation molecular sequencing methodologies in tandem with modeling complex communities allow insights into the role of the microbiome in health and disease states. Infection-related disease states in which dysbiosis is integral include late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), which still cause deaths and morbidity. Understanding microbiomic interactions may lead to alternative prevention, monitoring or treatment strategies, and modulation of long-term health outcomes especially in the preterm population. Recent studies have advanced understanding of the microbiome in NEC and LOS. RECENT FINDINGS: Mechanisms of host-microbiome interaction have been demonstrated. Patterns of microbiomic change in association with NEC and LOS have been observed, with community changes dominated by Proteobacteria and Firmicutes appearing to precede NEC, and very early microbiomic signatures influencing LOS. Data on viral and fungal elements are emerging. SUMMARY: Greater understanding of the neonatal bowel microbiome may allow tailored clinical practice and therapeutic intervention. Data handling and interpretation is challenging. Mechanistic studies of clinical interventions that affect the gut microbiome are important next steps.