Prenatal and postnatal antibiotic exposure influences the gut microbiota of preterm infants in neonatal intensive care units

Abstract

Background: To explore the influences of prenatal antibiotic exposure, the intensity of prenatal and postnatal antibiotic exposure on gut microbiota of preterm infants and whether gut microbiota and drug resistant strains in the neonatal intensive care unit (NICU) over a defined period are related.

Methods: Among 28 preterm infants, there were two groups, the PAT (prenatal antibiotic therapy) group (12 cases), and the PAF (prenatal antibiotic free) group (12 cases). Fecal samples from both groups were collected on days 7 and 14. According to the time of prenatal and postnatal antibiotic exposure, cases were divided into two groups, H (high) group (11 cases) and L (low) group (11 cases), and fecal samples on day 14 were collected. Genomic DNA was extracted from the fecal samples and was subjected to high throughput 16S rRNA amplicon sequencing. Bioinformatics methods were used to analyze the sequencing results.

Results: Prenatal and postnatal antibiotic exposure exercised influence on the early establishment of intestinal microflora of preterm infants. Bacteroidetes decreased significantly in the PAT group (p < 0.05). The number of Bifidobacterium significantly decreased in the PAT group and H group (p < 0.05). The early gut microbiota of preterm infants with prenatal and postnatal antibiotic exposure was similar to resistant bacteria in NICU during the same period.

Conclusion: Prenatal and postnatal antibiotic exposure may affect the composition of early gut microbiota in preterm infants. Antibiotic-resistant bacteria in NICU may play a role in reshaping the early gut microbiota of preterm infants with prenatal and postnatal antibiotic exposure.

Keywords: Anti-bacterial agents; Gastrointestinal microbiome; High-throughput nucleotide sequencing; Infant, premature; Intensive care unit, neonatal.

Fig. 1

a Shannon index of PAT and PAF groups on postnatal d7 and d14. b Colonization percentage of five gut bacteria in the PAT group. c Colonization percentage of five gut bacteria in the PAF control group. d Bacteriodetes in the PAT and PAF groups on d7 and d14

Fig. 2

Relative abundance of the main gut bacterial groups. a At the phylum level. b At the genus level. On d7 and d14, gut microbiota were generally dominated by the phyla Proteobacteria and Firmicutes, followed by Actinobacteria and Bacteroidetes. At the genus level, Klebsiella and Escherichia-Shigella were dominant. On d14, bacteria such as Bacteroides, Staphylococcus, Clostridium_sensu_stricto_1, Parabacteroides, and Bifidobacterium were more abundant than on d7

Fig. 3

Comparison of microbial communities by PCoA. PCoA was generated with OTUs (at 97% similarity) present in the different fecal samples. a PC1 vs. PC2. b PC1 vs. PC3. c PC2 vs. PC3

Fig. 4

LEfSe results on gut microbiomes of preterm infants. a Clustering tree. Different color areas represent different groups. The yellow nodes represent microbial taxa without significant differences between PAT and PAF groups. The red nodes represent microbial taxa that played an important role in the PAF group, and green nodes represent microbial taxa that played an important role in the PAT group. b Histogram showing the distribution of LDA values

Fig. 5

Comparison of the gut microbial communities in the H and L groups. a The Shannon index showed no significant difference between the two groups on d14 (p > 0.05). PCoA was generated with OTUs (at 97% similarity) present in the different fecal samples. b PC1 vs. PC2. c PC1 vs. PC3. d PC2 vs. PC3

Fig. 6

Relative abundance of different microbial groups in guts of preterm infants undergoing antibiotic prophylaxis at high/low doses. a At the phylum level. b At the genus level. On d14 gut microbiota were generally dominated by the phyla Proteobacteria (79.35% in the H group vs. 70.66% in the L group) and Firmicutes (19.33% in the H group vs. 14.81% in the L group). At the genus level, on d14 the microbiota structure in both groups was similar. The gut microbiota of the two groups remained predominantly populated with members of Klebsiella (55.91% in the H group vs. 36.15% in the L group) and Enterococcus (23% in the H group vs. 34.22% in the L group). Shigella and Streptococcus had a tendency to decrease in the H group

Fig. 7

Colonization percentage of five gut bacteria in the H group (> 7d) and L group (≤ 7d). The colonization of Bifidobacterium decreased more significantly in the H group than in the L group (5.47% in the H group vs. 10.24% in the L group, p < 0.05)

Fig. 8

LEfSe analysis showed significant differences in microbial community structure between the H and L groups. a Cladogram. b Distribution of LDA scores. Betaproteobacteria played an important role in the H group; in the L group, Bifidobacterium, Bifidobacteriaceae, and Bifidobacteriales were the prominent microbes