Enteric dysbiosis and fecal calprotectin expression in premature infants

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 week's 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.