Enteric dysbiosis and fecal calprotectin expression in premature infants

Pediatr Res. 2019 Feb;85(3):361-368. doi: 10.1038/s41390-018-0254-y. Epub 2018 Dec 10.

Abstract

Background: Premature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).

Methods: Stool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.

Results: We enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.

Conclusion: In premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Birth Weight
  • Dysbiosis / diagnosis*
  • Dysbiosis / microbiology
  • Enterocolitis, Necrotizing / microbiology
  • Feces / chemistry
  • Female
  • Gammaproteobacteria / isolation & purification
  • Gastrointestinal Microbiome
  • Gestational Age
  • Humans
  • Infant
  • Infant, Extremely Premature
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases
  • Infant, Very Low Birth Weight
  • Inflammation
  • Intensive Care Units, Neonatal
  • Klebsiella Infections / diagnosis
  • Leukocyte L1 Antigen Complex / analysis*
  • Male
  • Prospective Studies
  • RNA, Ribosomal, 16S
  • ROC Curve
  • Sensitivity and Specificity

Substances

  • Leukocyte L1 Antigen Complex
  • RNA, Ribosomal, 16S