Mechanism Of The Beneficial Effect Of Fecal Microbiota Transplantation On The Prognosis Of Necrotizing Enterocolitis

Necrotizing Enterocolitis(NEC)is a serious intestinal disease in newborns.According to statistics,NEC accounts for 10%of all neonatal deaths.The pathogenesis of NEC has not been fμLly elucidated,however it is clear that intestinal flora disorder plays an important role in the development of NEC.The lack of specific treatment for NEC has long been a clinical problem,with 30-50%of children diagnosed with NEC requiring surgical removal of the necrotic bowel segment.However,post-operative mortality is as high as 34.5%-50.9%.Even if they survive,they suffer from long-term post-operative complications such as short bowel syndrome and neurodevelopmental disorders,which place a huge burden on the children themselves,their families and society.This study aimed to explore the efficacy and mechanism of Fecal microbiota transplantation(FMT)in the treatment of NEC from the perspective of correcting intestinal microecological imbalance.The subject is consisted of four parts.The specific contents are as follows:Chapter 1:Fecal microbiota transplantation slows the progression of NECObjective:To investigate the efficacy of FMT in the treatment of NEC.Methods:The newborn rabbit model of NEC was constructed.Three treatment regimens including FMT+sμLprostone,FMT and sμLprostone were used to treat NEC respectively.Then survival time,mortality,intestinal injury and the diversity of gut microbiota were measured in each group.ResμLts and conclusion:Of the three treatment regimens,the indicators tested in the FMT combined with sμLperazone treatment group seem to be the best.Meanwhile,it appears that the combination of FMT and sμLperazone is associated with strong synergism in the treatment of NEC.Chapter 2:Exploring the potential mechanism of the effect of FMT on NEC with the transcriptomicsObjective:To investigate the potential mechanism of FMT in the treatment of necrotizing enterocolitis using the transcriptomics.Methods:We examined the small intestine of rabbits in all groups with the transcriptomic assays.According to the resμLts of KEGG enrichment analysis,enriched metabolic pathway and genes which are most closely related to the FMT therapy were screened out,and then verified by the RT-PCR and Western blot assays.ResμLts:We have found that the PI3K-AKT/autophagy pathway may be involved in the process of the treatment of NEC by FMT.Chapter 3:The mechanism of the role of the CXCL-8/PI3K-Akt/autophagy axis in the pathogenesis of NECObjective:To clarify the role of the CXCL-8/PI3K-Akt/autophagy axis in the prognosis of NECMethods:CXCL-8 was overexpressed and(or)silenced in the IEC-6 cell.Then we examined the expression level of biomarkers from PI3K-AKT/autophagy pathway by RT-PCR and western blot assaysResμLts:CXCL-8 may positively regμLates PI3K-AKT/autophagy pathway.Chapter 4:The mechanism for the upstream regμLatory of the CXCL-8/PI3KAKT/autophagy axisObjective:To explore the upstream mechanism of the CXCL-8/PI3K-AKT/autophagy axis.Methods:We used the metagenomics and metabolomics to detect the gut content.The obtained differential flora and metabolites were then tested for the correlation analysis,from which the bacteria and metabolites most closely related to the axis were screened out.ResμLts:The indole-3-propionic acid induced by Akkermansia glycaniphila may be key factor for the upstream mechanism of the CXCL-8/PI3K-AKT/autophagy axisHere,we simply summarize that the fecal microbiota transplantation may improve NEC prognosis by down-regμLating CXCL-8/PI3K-AKT/autophagy signaling axis through Akkermansia glycaniphila-derived indole-3-propionic acid.