Composition of gut microbiota varies in very low birth weight infants within six months after birth

Objective To investigate the diversity of gut microbiota and its dynamic changes in very low birth weight infants (VLBWIs) during the first six months after birth. Methods From January to December in 2015, 53 VLBWIs admitted to the Neonatal Intensive Care Unit (NICU) were recruited. Stool samples were collected from each subject on day 1, 7, 14 and 28 after birth as well as on day 180 during a follow-up visit. High-throughput 16S rRNA gene sequencing and bioinformatics analysis of bacterial DNA extracted from stool samples were performed using Illumina MiSeq platform double-end sequencing. Results (1) Phyla level: At all five time points, the dominant phyla were all Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. The median relative abundance of Proteobacteria was 0.598 5 (0.122 3~0.942 6) on day 1, then rose to 0.893 2 (0.478 1~0.987 0) after one week, maintained at 0.943 2~0.966 0 within 28 days, and later dropped back to the same level as day 1 on day 180 (all P<0.05). In contrast, the median relative abundance of Actinobacteria on day 180 was significantly higher than that on days 1, 7, 14 and 28 (all P<0.05). (2) Genus level: The relative abundance of Klebsiella increased significantly between days 7 and 28 as compared with the lower level on day 1 [0.326 5~0.368 2 vs 0.003 1(0.000 8~0.026 0), all P<0.05], but significantly decreased to a lower level on day 180 [0.008 1 (0.000 5~0.067 1)]. There was no significant difference in the relative abundance of Escherichia within 14 days after birth. However, it significantly increased since day 28 (P<0.05) and reached a peak on day 180 (P<0.05). Infants were born with a certain abundance of Bifidobacterium [0.000 5 (0.000 1~0.004 2)], which remained at a very low level for 28 days before reaching to a higher level of 0.045 1 (0.010 2~0.124 8) on day 180 (P<0.05). (3)The Shannon index on day 14 and 28 were lower than that of day 1 and day 180 (1.81±0.71, 1.89±1.270.56 vs 2.33±1.29, 2.2±0.5, all P<0.05), respectively. Conclusions The diversity of gut microbiota in VLBWIs decreases during NICU hospitalization as compared with that at birth when Proteobacteria and Klebsiella becoming the dominant bacteria. However, the diversity was regained after discharge with the increase of Bifidobacterium, Escherichia and other residential bacteria , which indicates that NICU hospitalization is a risk factor for dysbiosis in VLBWIs. Key words: Infant, very low birth weight; Gastrointestinal microbiome; RNA, ribosomal, 16S