Correlation Study Between Intestinal Flora And Neural Development In Preterm Infants With Hyperbilirubinemia

Objective:To explore the characteristics of intestinal flora of preterm infants with hyperbilirubinemia by 16 Sr DNA amplicon high-throughput sequencing technology,and to study the relationship between intestinal flora of preterm infants and neural development,so as to provide a theoretical basis for micro ecological therapy,prevention and treatment of hyperbilirubinemia in preterm infants and abnormal development of nervous system in early life.Methods:The late preterm infants treated in the Neonatal Department of the Second Hospital of Jilin University from November 2020 to November 2021 were selected as the research objects,and the stool and serum samples of 7-10 days were collected.The subjects were divided into hyperbilirubinemia group and non hyperbilirubinemia group.According to the obtained amplitude integrated electroencephalography（a EEG）results,preterm infants in hyperbilirubinemia group were divided into normal neurodevelopment group and abnormal neurodevelopment group.SPSS26.0 software was used to statistically analyze the clinical data and neurodevelopmental evaluation indexes of preterm infants,determine the species composition and abundance of intestinal flora of preterm infants by 16 Sr DNA amplicon high-throughput sequencing technology,and conduct bioinformatics analysis,and detect serum brain-derived neurotrophic factor（BDNF）by enzyme linked immunosorbent assay,the determination results were compared and analyzed.Results:1.According to the inclusion and exclusion criteria,47 preterm infants in the hyperbilirubinemia group,30 preterm infants in the non hyperbilirubinemia group,21 cases in the normal neurodevelopment group and 23 cases in the abnormal neurodevelopment group were selected.There was no significant difference between the two groups in maternal related factors and preterm related factors（general data,clinical indicators）.There were more abnormal results of head MRI and a EEG in preterm infants with hyperbilirubinemia than in preterm infants without hyperbilirubinemia.There were more abnormal results of head MRI and NBNA score in preterm infants with hyperbilirubinemia.The differences were statistically significant（P < 0.05）.2.The number of OTUs in hyperbilirubinemia group and non hyperbilirubinemia group were 4549 and 4986 respectively,and the number of common OTUs in the two groups was 2668.There was no significant difference in Shannon index between the two groups（P > 0.05）.PCo A and PCA analysis showed that the discrete trend of the principal components of the two groups was obvious,but there was no significant difference in Beta diversity index between the two groups（P > 0.05）.3.The top 4 flora in hyperbilirubinemia group and non hyperbilirubinemia group were proteobacteria,firmicutes,bacteroidota and actinobacteria.The results of t test and Lefse analysis showed that the abundance of burkholderiaceae / genus and clostridium-perfringens in preterm infants in hyperbilirubinemia group was significantly higher than that in non hyperbilirubinemia group,and the abundance of actinobacteria / class,bifidobacterium / family / genus,yersiniaceae,serratia,serratia-marcescens,bifidobacterium-animalis,rothia,rothia-mucilaginosa and micrococcaceae / genus was significantly lower than that in non hyperbilirubinemia group.4.In preterm infants with hyperbilirubinemia,the number of OTUs in the normal neurodevelopment group and the abnormal neurodevelopment group were3722 and 2616 respectively,and the number of common OTUs in the two groups was 1877.The Shannon index of preterm infants in normal neurodevelopment group was significantly higher than that in abnormal neurodevelopment group（P < 0.05）.PCo A and PCA analysis showed that the discrete trend of the principal components of the two groups was obvious,but there was no significant difference in Beta diversity index between the two groups（P > 0.05）.5.In premature infants with hyperbilirubinemia,the results of t test and Lefse analysis showed that the abundance of actinobacteria / class,xanthomonadales,corynebacteriales,burkholderiales,pseudomonas / genus,rothia,rothia-mucilaginosa,comamonadaceae and sphingomonas in the abnormal neurodevelopment group was significantly lower than that in the normal neurodevelopment group.6.The serum BDNF level in hyperbilirubinemia group was higher than that in non hyperbilirubinemia group（P < 0.05）.In premature infants with hyperbilirubinemia,the level of serum BDNF in abnormal neurodevelopment group was higher than that in normal neurodevelopment group（P < 0.05）.7.There was no correlation between serum BDNF and intestinal flora affecting hyperbilirubinemia preterm infants and their neural development.Conclusions:1.The intestinal flora of preterm infants with hyperbilirubinemia is mainly proteobacteria and firmicutes.The abundance of burkholderiaceae and clostridium-perfringens is high,and the abundance of species such as actinobacteria and bifidobacterium is low.2.There are more neurodevelopmental abnormalities in preterm infants with hyperbilirubinemia.There is a certain correlation between intestinal flora and early neurodevelopment.3.Serum BDNF is elevated in preterm infants with hyperbilirubinemia and neurodevelopmental abnormalities,which can be used as an evaluation index of neurodevelopment in preterm infants with hyperbilirubinemia.4.The decrease of the abundance of rothia may be a risk factor for the occurrence of hyperbilirubinemia and the development of nervous system in premature infants.