| BackgroundNeonatal jaundice is one of the most common diseases in the neonatal period,which can affect 80% premature infants and 60% full-term infants clinically.At present,the main treatment is blue light phototherapy,which can affect the colonization of neonatal intestinal flora.Previous studies have found that phototherapy can reduce the abundance of bifidobacteria and Lactobacillus in neonates,but combined with probiotics can significantly shorten the course of jaundice and reduce short-and long-term adverse reactions caused by phototherapy,achieving a synergistic effect.At present,the mechanism of action of phototherapy combined with animal bifidobacterium BB-12 in the treatment of neonatal jaundice is still unclear.In this study,phototherapy combined with animal bifidobacterium BB-12 was used to explore the effects of intestinal flora colonization,metabonomic changes and clinical efficacy.Whether animal bifidobacterium BB-12 can successfully colonize the intestinal tract of jaundice neonates and alleviate the near-and long-term adverse reactions of phototherapy needs to be verified by clinical studies.ObjectiveTo study the effects of phototherapy on the intestinal flora of neonatal jaundice,observe how the addition of bifidobacterium BB-12 affects the changes of neonatal intestinal flora,and analyze the metabolic pathway through which metabolites affect the colonization of intestinal flora through metabomics,so as to analyze the mechanism of the changes in flora.At the same time,the effect of bifidobacteria BB-12 supplementation on the efficacy of phototherapy was observed,to reduce the short-term and long-term adverse reactions and provide clinical basis for the rationality of adding probiotics to neonatal jaundice.Method1.A total of 25 neonates with jaundice who met the inclusion and exclusion criteria and met the indications of phototherapy were screened in the Hospital of Shanghai Sixth People’s Hospital at Lingang,and they were divided into the experimental group(n = 14)and the control group(n = 11).Their family members were included in this study after signing the informed consent before phototherapy,and followed up until 30 days after birth.2.The newborns in the experimental group were also given 0.3 m L of bifidobacteria BB-12 orally once a day,which contained 1 × 109 Conlony Forming Units(CFU),while the newborns in the control group only received blue light phototherapy.3.Fecal specimens were collected before,12 h,24 h,36 h of phototherapy and 10 d,20 d,30 d after delivery.Based on 16 S r RNA metagenomic DNA sequencing technology,the composition and abundance of newborn intestinal microorganisms,alpha diversity,beta diversity,family and species level of microbial differences,and network map were analyzed for multi-factor comprehensive evaluation.4.The metabolic pathways and their products were targeted by metabolomic liquid chromatography-mass spectrometry(LC/MS)in fresh stool samples collected from clinical trials,and the biological information was analyzed and described.5.SPSS 21.0 statistical software was used to process the data,and one-way ANOVA,Mann-Whitney test,T-test and Chi-square test were used to compare the differences between groups.Results1.Metagenomic sequencing results:(1)Analysis of microbiota composition structure: phototherapy could cause a significant decrease in the number of operational taxonomic units(OTUS),and the number of OUTS gradually recovered after stopping phototherapy.Phototherapy had less effect on the changes of microbiota in the experimental group.(2)Analysis of Alpha diversity:After phototherapy,the richness and diversity of microbiota increased first and then decreased,and with the increase of time,the diversity and richness would gradually recover to that before phototherapy.(3)Beta diversity analysis: phototherapy affected the changes of microbiota,and there was a statistical difference in the experimental group,but no statistical difference in the control group.(4)Bacterial flora analysis at the family level:Phototherapy affected the abundance of bifidobacteriaceae,and there was no statistical difference between the two groups before and after the control and the two groups at the same time,but phototherapy had less effect on the changes of bifidobacteriaceae in the experimental group.(5)Analysis of genus bacteria:Phototherapy affects the changes of bifidobacterium;The experimental group showed an upward trend,while the control group showed a downward trend.There was no statistical difference between the two groups.There was no statistical difference between the two groups at the same time,and the effect of phototherapy on the change of bacterial genera in the experimental group was smaller.(6)Horizontal flora analysis:Phototherapy affected the changes of bifidobacteria in animals,and there was a statistical difference between the experimental group and before phototherapy.And with the increase of time,the difference of intestinal flora between the two groups became more and more obvious.(7)Linear discriminant analysis Effect Size(Lef Se)analysis showed that there were more different species in the control group than in the experimental group.2.Metabolomics results:(1)Principal components analysis(PCA)showed that there were significant differences in metabolite composition between the two groups.(2)Analysis of differential metabolites:There were significant differences in the metabolites between the experimental group and the control group.(3)Enrichment analysis:There were 48 metabolic pathways enriched in the experimental group and 31 metabolic pathways enriched in the control group,indicating that the influence of the experimental group on metabolism was significantly higher than that of the control group.3.Clinical results: The incidence of daily stool >3 times in the experimental group was lower during the blue light treatment(P< 0.05).ConclusionThe results showed that oral administration of bifidobacterium bifidum BB-12 could affect the changes of intestinal flora,improve intestinal motility,regulate intestinal function and reduce the frequency of defecation in children.Meanwhile,animal bifidobacterium BB-12 enriched the number of bifidobacterium,ensured the propagation of beneficial bacteria,inhibited the growth of harmful bacteria,and avoided the change of intestinal flora diversity.Bifidobacterium is involved in bilirubin metabolism.Animal bifidobacterium BB-12 affects neonatal metabolic pathway and increases beneficial metabolites,which is speculated to be realized through bile acid metabolic pathway.At least within a few weeks of administration,bifidobacterium animalis BB-12 can colonize the intestinal tract of children with jaundice.Bifidobacterium animalis BB-12 is a potential marker of neonatal jaundice and may provide a new target for clinical treatment of neonatal jaundice. |
PDF Full Text Request