Distortions in Development of Intestinal Microbiota Associated with Late Onset Sepsis in Preterm Infants

TLDR

Late‑onset sepsis is a leading cause of morbidity and mortality in preterm infants, and disruptions of the normal gut microbiota may increase LOS risk by compromising the mucosal barrier. The study aimed to correlate intestinal microbiota distortions with LOS to inform microbiota‑based screening and early intervention strategies. In a nested case‑control cohort of 10 LOS and 18 matched preterm infants, stool samples were collected prospectively and analyzed by 16S rRNA sequencing to assess diversity and bacterial signatures. LOS infants showed lower α‑diversity two weeks before diagnosis, distinct microbiota structure 1–2 weeks prior, reduced Bifidobacteria, and a loss of many OTUs present in controls, supporting that microbiota distortion—not pathogen enrichment—underlies LOS.

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.