Characteristics of the Intestinal Microbiota in Very Low Birth Weight Infants With Extrauterine Growth Restriction

Abstract

Objective: Very low birth weight (VLBW) infants, which experience significant postnatal growth restriction at the time of discharge, are at high risk of later growth failure and long-term consequences. This study aims to characterize the structure of intestinal microbiome community in VLBW infants with extrauterine growth restriction (EUGR). Methods: Twenty-three VLBW infants appropriate for gestational age (GA) hospitalized at the neonatal intensive care unit of the BaoAn Maternal and Child Care Hospital (Shenzhen, China) were enrolled in this study, which were divided into the growth restriction group (EUGR; n = 12) and the normal growth group (AGA; n = 11). Meconium and fecal samples at postnatal day 28 were collected respectively during hospitalization. Total bacterial DNA was extracted and sequenced using the Illumina MiSeq Sequencing System based on the V3-V4 hyper-variable regions of the 16S rRNA gene. Results: The intestinal bacterial communities of preterm infants were dominated by the phylum Proteobacteria. Compared with the AGA group, the relative abundances of the genera Aeromicrobium and Serratia in meconium samples significantly decreased, whereas genera Parabacteroides, Ruminococcus, Blautia, and Aeromonas were more prevalent in the EUGR group. On postnatal day 28, the relative abundances of the genera Parabacteroides, Bacteroides, Eubacterium, Granulicatella, and Salinivibrio were significantly different between the two groups, where genus Salinivibrio decreased significantly in the EUGR samples. Among them, genus Parabacteroides was more abundant on both postnatal day 1 and 28. Further KEGG prediction analysis showed that there were many differences in functional genes and pathways between the two groups on postnatal day 28, but not on day 1, the majority of which were related to energy metabolism. And no statistical differences were observed in the clinical characteristics of infants. Conclusions: Overall, these findings showed that a distinct gut microbiota profile presented in preterm infants with EUGR. The role of intestinal microbiome in the extrauterine growth of preterm infants during hospitalization should be further investigated.

Keywords: 16S rRNA sequencing; extrauterine growth restriction; gut microbiome; neonatal intensive care unit; preterm infants; very low birth weight.

Figure 1

Overall structures of intestinal microbiota at the phylum level. (A) Average microbiome community of group EUGR and AGA. (B) Microbiome community structure of each sample at d1. (C) Microbiome community structure of each sample at d28. (D) Differences of phylum between EUGRd1 and AGAd1 group. (E) Differences of phylum between EUGRd28 and AGAd28 group.

Figure 2

Principal coordinate analysis and alpha diversity plots in intestinal microbiota. (A) Weighted UniFrac PCoA plot based on OTU abundance. Each point represents the intestinal microbiota of a newborn in the EUGR group (red) and AGA group (green). (B) Comparison of the microbiome biodiversity between infants with EUGR and normal growth, the Shannon index, Simpson index were shown as estimators.

Figure 3

Histogram of the LDA scored for differentially abundant genera between EUGR and AGA groups (red: AGA; green: EUGR). LDA scores were calculated by LDA effect size using linear discriminant analysis. (A) was d1, and (B) was d28.

Figure 4

Differently abundant pathways between EUGR and AGA groups and its relationship with varying abundances of genera. (A) Functional properties that differed significantly between EUGRd28 and AGAd28 groups. (B) Relationships among bacteria, functional genes, and metabolic pathways.