Preliminary Study On The Mechanism Of Lipid Metabolism Mediated By Microbiome In The Regulation Of Radiation Enteritis

Background and Objectives:Radiation enteritis(RE)is a common complication in cancer patients receiving pelvic and abdominal radiotherapy,which seriously affects the quality of life of the patients.In recent years,with the wide application of radiotherapy and the significant extension of the survival time of cancer patients,the prevalence of RE is also increasing,which is an urgent medical problem to be solved.Although studies have shown the changes of this disease at clinical,pathological and other levels,its related pathophysiological mechanism is still unknown.Recent studies have shown that intestinal microorganisms play a important role as a key regulatory element in the physiological and pathological state of the host,However,the microbial changes of RE and its functional mechanism are hitherto unclear.The purpose of this study was to explore the relationship between metabolic changes caused by dysbiosis and RE through high-throughput 16S rDNA sequencing and global lipidomics analysis,in order to clarify the crosstalk mechanism among radiation injury,gut microbiota and host metabolism.Methods:Firstly,by delivering single high-dose irradiation,a preclinical animal model of RE was established.Then high-throughput 16S rDNA sequencing was performed to examine the changes of gut microbiota in mice with acute or chronic RE and the related differential bacteria were further identified.Addiationally,PICRUSt was used to predict metabolic profiles of bacterial communities in RE.The characteristic changes of lipid metabolism in acute and chronic RE were further verified through global lipidomics analysis by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry(HPLC-ESI-MS/MS).Ultimately,through multi-omics analysis,the crosstalk mechanism among radiation injury,gut microbiota and host metabolism was explored and the most significant relationship between bacteria and lipid metabolism was effectively identified.Results:We succeed in establishing a well-characterized animal model of RE,which exhibits an amazing symptomatological,pathological and imageological similarity to Homo sapiens.16S datasets revealed that localised irradiation dramatically altered the gut microbial composition.The observed species number and shannon diversity index of gut microbial remarkably decrease in irradiated mice and fluctuate during the RE progression.Through the functional prediction by PICRUSt,we found that the disorder of intestinal flora may lead to the change of lipid metabolismin the host.These observations were largely confirmed by the global lipidomics analysis of tissues from irradiated mice.Besides,spearman correlation analysis identified that seven bacteria-metabolite pairs showed the most significant functional correlation in RE,including Alistipes-PC(36:Oe),Alloprevotella-LPC(17:1),Bacteroides-DG(18:0/20:4),Dubosiella-PC(35:2),Eggerthellaceae-PC(35:6),Escherichia-Shigella-TG(18:2/18:2/20:4)and Lactobacillus-PC(17:0/22:6)(r?±0.8).Conclusion:Our study provided a comprehensive description of microbiota dysbiosis and lipid metabolic disorders in RE,suggesting strategies to change local microecosystem to relieve radiation injury and maintain homeostasis.12 genus of bacteria,18 lipid classes and 138 lipid metabolites were closely related to the disease progression of RE.The seven bacteria-metabolite pairs are worthy of further study,which provides a new direction for exploring the crosstalk mechanism among radiation injury,gut microbiota and host metabolism.