Correlation Between Intestinal Flora And Early Nervous System Development In Premature Infants With Respiratory Distress Syndrome

Objective:To detect the intestinal microflora of premature infants with respiratory distress syndrome,understand the abundance and diversity of intestinal microflora of premature infants with RDS,and to further explore the potential relationship between intestinal microflora and neurodevelopment of premature infants,so as to provide theoretical basis for probiotic therapy and open up a new way for early treatment and prevention of nervous system diseases of premature infants.Methods:The meconium and 10-14-day fecal samples of all premature infants hospitalized in the Department of Neonatal Pediatrics,the second Hospital of Jilin University from September 2020 to February 2021 were collected.According to the inclusion criteria and exclusion criteria,a total of 44 premature infants and 88 fecal samples were selected.According to the score of neonatal amplitude integrated-electroencephalogram and neonatal neurobehavioral score,88 stool samples were divided into two groups: neurodevelopmental group(group A)and neurodysplasia group(group B).The general data of premature infants were statistically analyzed,and the stool samples were sequenced by 16 Sr DNA technique.The abundance and characteristics of intestinal flora of premature infants with RDS in each group were analyzed.Results:1.There was no significant difference between NBNA score and a EEG in the evaluation of nervous system development,but gestational age and feeding mode had statistical significance on NBNA score and EEG results.2.A total of 88 fecal samples of RDS premature infants were tested,2 cases of meconium were sequenced and the database was established successfully,42 cases of amplification sequence could not meet the standard of database construction,43 cases of fecal samples were amplified successfully and 1 case failed in 10-14 days.3.The Shannon index of normal neurodevelopment group and Shannon index of neurodysplasia group of RDS preterm infants were1.97(1.12,2.87)and 1.67(0.69,2.38)respectively.There was significant difference between the two groups(P < 0.05).The α diversity of neurodysplasia of prematurity was higher than that of neurodysplasia of prematurity,but there was no significant difference in β diversity between groups.4.The intestinal flora of RDS premature infants are mainly Firmicutes and Proteobacteria.At the genus level,the neurodevelopmental groups of premature infants are mainly Klebsiella,Enterococcus,Streptococcus,Clostridium and Bacteroides,while the neurodysplasia groups are mainly Klebsiella,Enterococcus,Staphylococcus,Acinetobacter baumannii and Serratia.5.The results of Lefse analysis showed that the abundance of Enterococcus increased in the normal neurodevelopmental group and the abundance of Yersinaceae and Serratia increased in the premature neurodysplastic group.6.According to the results of a EEG,the α diversity in the normal group was higher than that in the abnormal group,but there was no significant difference between the two groups.Lefse analysis showed that Streptococcus and Clostridium butyricum were enriched in the a EEG normal group.7.Re-grouped according to the feeding mode,the α diversity in the mixed feeding group was higher than that in the milk powder feeding group,but there was no significant difference in β diversity between the two groups.Lefse analysis showed that Actinomycetes phylum / class,Micrococci order / family,Streptococcus family / genus were enriched in the mixed feeding group.8.Re-grouped according to gestational age,the intestinal microfloraα diversity of premature infants with gestational age > 34 weeks was higher than that of premature infants with gestational age < 34 weeks,but there was no significant difference among β diversity groups.Actinomycetes / class,Micrococcaceae / genus,Streptococcus / genus,Clostridium butyricum were enriched in premature infants with gestational age > 34 weeks Conclusions:1.The meconium of RDS premature infants is not aseptic,and the number and diversity of intestinal flora increase with the increase of postnatal age.2.The intestinal flora of RDS premature infants is mainly Firmicutes and Proteobacteria.At the genus level,Klebsiella and Enterococcus are the dominant flora.The microflora of premature infants has the characteristics of low diversity and high difference among individuals.3.The feeding mode and gestational age may affect the early nervous system development of RDS premature infants by changing the intestinal flora.4.Intestinal flora is related to the early neurodevelopment of RDS premature infants.The increased abundance of Serratia and the decrease of Clostridium butyricum abundance may be the risk factors of neurodysplasia in premature infants.