Impact of Prematurity and Perinatal Antibiotics on the Developing Intestinal Microbiota: A Functional Inference Study

Abstract

Background: The microbial colonization of the neonatal gut provides a critical stimulus for normal maturation and development. This process of early microbiota establishment, known to be affected by several factors, constitutes an important determinant for later health.

Methods: We studied the establishment of the microbiota in preterm and full-term infants and the impact of perinatal antibiotics upon this process in premature babies. To this end, 16S rRNA gene sequence-based microbiota assessment was performed at phylum level and functional inference analyses were conducted. Moreover, the levels of the main intestinal microbial metabolites, the short-chain fatty acids (SCFA) acetate, propionate and butyrate, were measured by Gas-Chromatography Flame ionization/Mass spectrometry detection.

Results: Prematurity affects microbiota composition at phylum level, leading to increases of Proteobacteria and reduction of other intestinal microorganisms. Perinatal antibiotic use further affected the microbiota of the preterm infant. These changes involved a concomitant alteration in the levels of intestinal SCFA. Moreover, functional inference analyses allowed for identifying metabolic pathways potentially affected by prematurity and perinatal antibiotics use.

Conclusion: A deficiency or delay in the establishment of normal microbiota function seems to be present in preterm infants. Perinatal antibiotic use, such as intrapartum prophylaxis, affected the early life microbiota establishment in preterm newborns, which may have consequences for later health.

Keywords: antibiotics; infants; intestinal microbiota; microbiome; preterm.

Figure 1

Aggregate microbiota (%) at phylum level in fecal samples from full-term, vaginally delivered, exclusively breast-fed (FTVDBF) vs. preterm infants at the different time points analyzed.

Figure 2

Concentration (mean ± SD) of the main SCFAs (acetate, propionate, and butyrate) and total SCFAs in fecal samples from full-term, vaginally delivered, exclusively breast-fed (FTVDBF) vs. preterm infants at the different time points analyzed (2, 10, 30, and 90 days). Asterisks indicate statistically significant differences (* p < 0.05; ** p < 0.01, *** p < 0.001).

Figure 3

Relative abundance (%) of phylum level distributions of the fecal microbiota in the different antibiotic exposure groups classified into four classes depending on mother and infant antibiotic exposure at 30 days of life.

Figure 4

Relative frequencies (mean ± SD) of KEGG pathways (level 2) belonging to the categories that showed statistically significant differences among the four different antibiotic exposure groups at 30 days of life. Different letters above columns within the same KEGG category indicate statistically significant differences (p < 0.05 and q < 0.25).