Late-onset sepsis treatment in very preterm infants alters longitudinal microbiome trajectory with lower abundance of Bifidobacterium despite probiotic supplementation.

INTRODUCTION

Taxonomic instability within the dynamic gut microbiome of very preterm infants can be associated with various adverse outcomes. This longitudinal study was designed to follow the trajectory of microbiome composition and abundance in a cohort of probiotic supplemented very preterm infants with and without sepsis.

METHODS

Stool samples (n = 180) from probiotic-supplemented participants with culture-positive sepsis (n = 8) and matched healthy controls (n = 10) were analyzed using 16S rRNA sequencing. Calculation of total copy number per gram (TCN/g) by DNA spiking provided estimates of total microbial load.

RESULTS

TCN/g was significantly different between infants with and without sepsis, the latter having more rapid increase and overall higher TCN/g. In adjusted analysis, sepsis was associated with a significant abundance of Escherichia-Shigella (p = 0.02) and Veillonella (p = 0.01). Microbial load and composition appeared to fluctuate following antibiotic administration. Analysis of pre-sepsis samples showed a non-significant trend toward lower Bifidobacterium abundance and higher Escherichia-Shigella abundance in infants with subsequent sepsis. Antibiotic administration was independently associated with significantly lower (on average 250-fold lower) Bifidobacterium (p = 0.005) abundance, which remained significant after adjustment for confounders.

CONCLUSIONS

Estimation of absolute abundance reveals fluctuations and blooms in key genera within the gut microbiome of very preterm infants that may not be recognized using relative abundance alone. Very preterm neonates with sepsis have a significantly different longitudinal trajectory of microbiome development, which may, in part, extend to lower Bifidobacterium and higher Escherichia-Shigella abundance prior to the onset of sepsis. Bifidobacterium abundance appears to be particularly affected by antibiotic administration compared to other genera.