Using Multi-omics To Explore Effect Of Fecal Microbiota Transplantation On Post-weaning Diarrhea Piglets

Early weaning is easy to cause post-weaning diarrhea of piglets.Many studies have found that gut microbial dysbioses occurs in piglets with diarrhea caused by different etiology.Fecal microbiota transplantation as a method of targeted reconstruction of host intestinal microbiota seems to have a certain effect on the treatment of related intestinal diseases and alleviate of diarrhea symptoms.In this study,Taihu piglets with similar body weight and health condition were early-weaned at the age of 21 days,were used as experimental animals.Set up healthy group,diarrhea control group and fecal microbiota transplantation group.The experiment ended at the age of 66 days.The diarrhea and death of piglets during the experiment were statistical.The changes of intestinal microbial of piglets in three groups at 21,34,38 and 66 days were analyzed by 16 S r RNA sequencing.The characteristics of fecal metabonomic of piglets at 34 days in different groups were analyzed by non-targeted metabonomics.The tissues of jejunum,colon,liver,spleen and oral mucosa of piglets at 66 days were compared and analyzed by transcriptome.The relative expression of intestinal barrier related genes(TLR,MUC)was measured by RT-PCR.The purpose of this study was to explore the effects of fecal microbiota transplantation on gut microbiota,metabonomic and transcriptome of jejunum,colon,liver,spleen and oral mucosa in post-weaning diarrhea piglets,and to evaluate the therapeutic potential of fecal microbiota transplantation on weaned piglets with diarrhea.The main results are as follows:(1)Fecal microbiota transplantation could partially alleviate the diarrhea symptoms of piglets and reduce the mortality of diarrhea.The diarrhea rate,diarrhea index and mortality of piglets in fecal microbiota transplantation group has a tendency to decline at the age of28-65 days(P>0.05).(2)Fecal microbiota transplantation could partially restore the diversity and composition of gut microbiota of diarrhea piglets and significantly increase the relative abundance of beneficial bacteria.At the age of 34 and 38 days,There was no significant difference in Alpha diversity between the fecal bacteria transplantation group and the healthy group,and between the fecal bacteria transplantation group and the diarrhea control group(P>0.05).The Beta diversity of the fecal microbiota transplantation group was more similar to that of the healthy group.There were no significant difference of gut microbiota diversity among the three groups at the age of 66 days(P>0.05).For the compositions of the gut microbiota,fecal microbiota transplantation significantly increased the relative abundance of beneficial bacteria such as Spirochaetae(34 d)and Phascolarctobacterium(66 d)(P<0.05).In addition,Streptococcus(38 d),unclassified Prevosiaceae(66 d)and so on are the biomarkers of diarrhea control group and may be the key pathogens causing diarrhea in piglets,while Phascolarctobacterium(66 d)are the biomarkers of fecal microbiota transplantation group and may be the key bacteria related to fecal microbiota intervention.Spirochaetae(34 d and 66 d),Lachnospiraceae(34 d)and so on are the biomarkers of healthy groups,which may be related to the maintenance of intestinal health of piglets.(3)Fecal microbiota transplantation significantly improved the abnormalities of lipids and lipid-like molecules metabolites and sphingolipid metabolism pathways in feces of diarrhea piglets.At the age of 34 days,the main metabolites were lipids and lipid-like molecules among the healthy group,the fecal microbiota transplantation group and the diarrhea control group.The differential metabolites between fecal microbiota transplantation group and diarrhea control group,and between healthy group and diarrhea control group were significantly enriched in the pathways of apoptosis,sphingolipid metabolism and glutathione metabolism(FDR<0.05).There is only one pathway for significant enrichment of differential metabolites between fecal microbiota transplantation group and healthy group,which is tryptophan metabolism(FDR<0.05).(4)Fecal microbiota transplantation from the transcription level significantly affected the PPAR signaling pathways,AMPK pathway of diarrhea piglets in colon and liver(P<0.05),significantly affected linoleic acid metabolism pathway in jejunum and colon,and B cell receptor signaling pathways in jejunum(P<0.05),At the same time,fecal microbiota transplantation significantly up-regulated the expression of ELL3 and PAX5,while down-regulated the expression of CHAC1 in the jejunum and colon(FDR<0.05),and significantly increased the relative expression level of MUC2 in colon(P<0.05).presumably,fecal microbiota transplantation plays an important role in maintaining the homeostasis of lipid metabolism and improving the function of immune and intestinal barrier in diarrhea piglets.In a word,post-weaning diarrhea seriously affects the survival rate of piglets,and fecal microbiota transplantation helps to reverse the gut microbial dysbioses,metabolic disorder and improve the of immune and gut barrier function of diarrhea piglets,and reduce the harmfulness of post-weaning diarrhea.