Abstract
Late onset sepsis (LOS) is a major contributor to neonatal morbidity and mortality, especially in premature infants. Distortions in the establishment of normal gut microbiota, commensal microbes that colonize the digestive tract, might increase the risk of LOS via disruption of the mucosal barrier with resultant translocation of luminal contents. Correlation of distortions of the intestinal microbiota with LOS is a necessary first step to design novel microbiota-based screening approaches that might lead to early interventions to prevent LOS in high risk infants. Using a case/control design nested in a cohort study of preterm infants, we analyzed stool samples that had been prospectively collected from ten preterm infants with LOS and from 18 matched controls. A 16S rRNA based approach was utilized to compare microbiota diversity and identify specific bacterial signatures that differed in their prevalence between cases and controls. Overall α-diversity (Chao1) was lower in cases two weeks before (p<0.05) but not one week before or at the time of diagnosis of LOS. Overall microbiota structure (Unifrac) appeared distinct in cases 2 weeks and 1 week before but not at diagnosis (p<0.05). Although we detected few operational taxonomic units (OTUs) unique or enriched in cases, we found many OTUs common in controls that were lacking in cases (p<0.01). Bifidobacteria counts were lower in cases at all time points. Our results support the hypothesis that a distortion in normal microbiota composition, and not an enrichment of potential pathogens, is associated with LOS in preterm infants.
Highlights
As newborn infants mature, a community of intestinal bacteria begins to establish a commensal and/or symbiotic relationship with the host
Our study was able to benefit from a prospective cohort design, which allowed us to analyze fecal samples collected before the onset of clinical disease
While the intestinal microbiota development at a molecular level has already been well documented in animal models to correlate with gastrointestinal (GI) tract development, mucosal integrity, and even nutritional status, these correlations have only recently begun to emerge for human term infants
Summary
A community of intestinal bacteria begins to establish a commensal and/or symbiotic relationship with the host. This relationship supports several favorable processes that maintain and strengthen the intestinal mucosal barrier. High throughput molecular technologies provide sufficient detail about intestinal microbiota to allow novel insights into the nature and implications of deviations of intestinal bacterial colonization in preterm infants from normal patterns in healthy infants. Previous studies using high throughput sequencing methods from our group have shown that meconium in preterm infants contains microbial DNA, [9] that the diversity of microbes in preterm infants increases over time, and that the microbial ecology of the gut in infants who subsequently develop NEC differs from that of closely matched controls [10]
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