Preterm Infants with Bronchopulmonary Dysplasia Develop a Less Diverse Intestinal Microbiome

Purpose: The study of the developing microbiome in the context of neonatal health and disease is a rapidly expanding area of interest. There is a complex relationship between the development of the gastrointestinal microbiota and the regulation of immune function. Preterm infants with developmentally immature lungs are more susceptible to the development of bronchopulmonary dysplasia (BPD), a debilitating lung disease leading to significant morbidity. The role of the intestinal microbiome in the pathogenesis of BPD has not yet been investigated. The purpose of this study is to elucidate the differences in the intestinal microbiota between preterm infants who develop BPD and those who do not, as well as the effect of early antibiotic exposure on the neonatal microbiota in these cohorts. Methods: Stool specimens were collected from very low birth weight (VLBW) infants born < 1500 g BW during the first six weeks of life. Bacterial DNA was isolated, and sequences targeting the V4 region of the 16S rRNA gene were generated on the Illumina MiSeq platform with a median of 23,492 sequences generated per sample. Following quality filtering, sequence clustering into operational taxonomic units (OTUs) and taxonomic assignment for each OTU, the overall bacterial diversity and relative abundance were determined in each sample. BPD was defined as need for supplemental oxygen >21% for >28 days. The primary outcome was diversity of gut microbiota at the genus level among infants with/without BPD, along with antibiotic exposure taken into consideration for each comparison. Results: Among preterm infants exposed to early antibiotics, microbial diversity was significantly decreased in those who developed BPD compared to those who did not (Figure 1). In infants who developed BPD and were exposed to antibiotics, there is a significant increase in the relative abundance of Escherichia/Shigella and Streptococcus in comparison to infants that developed BPD without antibiotic exposure. Among the antibiotic exposed cohort, the relative abundance of Veillonella is significantly decreased in infants with BPD compared to the infants who did not develop BPD (Figure 2). Conclusions: Our study suggests that VLBW infants who develop BPD have decreased microbial diversity and display significant changes in the composition of their intestinal microbiota compared to those without BPD. Early antibiotic exposure also leads to distinct microbiota changes in this cohort. These results highlight