Composition Of Gut Microbiota In Very Low Birth Weight Infants And The Relationship With Late-Onset Infection Within Six Months After Birth

Aims This study aimed to explore the diversity of gut microbiota and its dynamic changes in very low birth weight infants(VLBWIs)during the first six months after birth.Using the Illumia MiSeq high-throughput sequencing technology to study the DNA of stool samples,and to perform 16 S rRNA gene high-throughput sequencing and bioinformatics analysis.The relative abundance and diversity of gut microbiota at different time points were compared ? the characteristics of gut microbiota and the relationship with late-onset infection were further studied,which was used to provide an important experimental basis for the treatment of diseases in very low birth weight infants.Methods The research subjects in this study were to recruit 53 VLBWIs admitted to the Neonatal Intensive Care Unit(NICU)from January to December in 2015.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.And 53 children were divided into late-onset and non-infected groups to explore the correlation between late-onset infection and gut microbiota.High-throughput 16 S rRNA gene sequencing and bioinformatics analysis of bacterial DNA extracted from stool samples were erformed 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 1on 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(0.0001~0.004 2)],which remained at a very low level for 28 days before reaching to a higher level of0.045 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.(4)Correlation analysis of late-onset infection: In 53 VLBWI,26 cases had late-onset infection.The duration of PICC use,total enteral feeding,duration of antibiotic use,length of hospital stay,and corrected gestational age at discharge were higher than the controlgroup(P < 0.05).The gestational age and birth weight of the late-onset infection group were significantly lower than those of the control group(P<0.05).There was no significant difference in gender?mode of delivery?using probiotics?NEC?either discharged weight between the two groups.Late-onset infection had different effects on the level of each phylum and genus.The after birth.The relative abundance of LID group on the first day was significantly lower than NLID(P<0.05);on the 7th day,the relative abundance of Staphylococcus in the LID group was higher(P<0.05);on the 14 th day,there is no significantly difference between two groups(P>0.05).On the 28 th day,the relative abundance of Escherichia in LID group was significantly lower.On the contrary,the relative abundance of proteobacteria in LID group was significantly higher(P<0.05);on the 180 th day,the relative abundance of Bifidobacteria in the LID group was significantly lower(P<0.05).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.It is necessary to adopt appropriate measures such as reducing antibiotic use,minimizing invasive surgery,and using probiotics to reduce risk of infection.