Beneficial Effects of Probiotic Treatment on Gut Microbiota in Very Low Birth Weight Infants

Abstract

The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiota. In the present study, a total of 36 VLBW infants were randomly divided into two groups, who were treated with combined probiotics and placebo, and 72 fecal specimens on days 14 and 28 of life were collected from them. Finally, 32 fecal specimens extracted from 16 preterm VLBW infants were qualified and analyzed using 16S rRNA gene sequencing. The primary outcome was to evaluate the change of gut microbiota in VLBW infants after combined probiotic supplement. The secondary outcome was to analyze the correlation gut microbial composition and levels of cytokines. We found that probiotic treatment, but not placebo, decreased the α-diversity of gut microbiota in VLBW infants. At the phylum level, probiotic treatment strongly increased the abundance of Firmicutes, whereas that of Proteobacteria was significantly reduced. At the family level, Streptococcaceae and Lactobacillaceae became prevalent after probiotic treatment, while the relative abundance of Enterobacteriaceae was reduced in the meantime. Most notably, significant correlations were observed between Lactobacillaceae abundance and serum cytokine levels. Further studies are required to shed more light on the characteristics of gut microbiota of VLBW neonates. And the modulation of microbiota should be considered to improve the survival rate of VLBW infants.

Figure 1

The flowchart of the present study.

Figure 2

The changes of α-diversity in the PB group (a–d) and the PL group (e–h).

Figure 3

Principal coordinate analysis (PCoA) on the fecal microbiota of the PB group (a) and the PL group (b). 14-day and 28-day samples are shown in separate panels to emphasize the temporal difference.

Figure 4

Cladogram generated by the LEfSe method indicating differences in the bacterial taxa between 14-day and 28-day samples from the PB group. Nodes in red indicate bacteria that were enriched on 28-day neonates, while nodes in blue indicate bacteria that were enriched on 14-day neonates.

Figure 5

The significant changes in serum levels of IL-6 (a) and TGF-β2 (b) in the PB group.

Figure 6

Correlation between the differential abundance of bacteria and the change of cytokines. Pearson's correlation coefficient (r) and two-tailed probability (p) were used to evaluate statistical importance.