Exploring The Molecular Regulatory Mechanism Of Different Body Weights In Meat Rabbits Based On Multi-Omics

As an important growth performance index of meat rabbits,body weight is related to the production level and economic benefits of the meat rabbit industry.However,under the same feeding and management conditions,significant low body weight,decreased fecundity,and prolonged marketing time have occurred,and no relevant molecular mechanism of meat rabbit body weight has been reported.Therefore,it is imperative to explore the molecular regulation mechanism of different body weight of meat rabbits.In this study,12 Tianfu black rabbits of low body weight recombination(CG group)and standard weight group(EG group)in good health at the age of 70 days were selected as test materials.Cecum tissues and contents were collected for metagenomics,metabonomics and transcriptome sequencing,and cecum histomorphology was observed,and inflammatory factors and sequences were determined,exploring and analyzing the molecular regulatory mechanisms related to the weight of meat rabbits,the research results are as follows:(1)Body weight results and intestinal histologyThe weight difference between the 70-day-old EG group(2,295 ±40 g)and CG group(CG:1,709 ±44 g)was significant(P < 0.01),and the average daily weight gain of the CG group was significantly lower than that in the EG group(P < 0.01).The EG group had steatosis in the epithelial cells of the cecum mucosal layer,while the inflammatory cells in the cecal mucosal layer and propria in the CG group were infiltrated significantly,the mucosal epithelium was significantly necrotic and shed,and the thickness of the mucosal layer was significantly lower than that in the EG group(P < 0.01);the goblet cells of the cecum in the EG group were structurally intact and the structure of the crypt was relatively intact,while the goblet cells of the cecum in the CG group had low structural integrity and disordered arrangement,and the proportion of goblet cells was significantly reduced compared with the normal group(P < 0.05).(2)Microbial flora composition and functional analysis resultsThe results of metagenomic sequencing showed that only bacteria were significantly different between the two groups of rabbits(P < 0.05).Compared with the EG group,the relative richness of the phylum Verrucomicrobia,Firmicutes,and Actinobacteria was significantly increased in the CG group(P < 0.05),while the relative abundance of Bacteroides was significantly reduced(P < 0.05);at the genus level,the relative abundance of Clostridium was significantly reduced(P < 0.05)and the relative abundance of Bacteroides was significantly increased(P < 0.05),but at the species level,the first 20 bacterial species were not significantly different between the two groups(P > 0.05).The functional enrichment analysis results showed that the c GMP-PKG signaling pathway,alcohol metabolism,and GABA biosynthesis signaling pathway were significantly enriched in the CG group(log2FC > 1,P < 0.05).In addition,LEf Se analysis of the KEGG module showed that modules related to amino acid metabolism modules as well as a cofactor and vitamin metabolism were enriched in the CG group.Compared with the EG group,CAZymes spectras,which encode glycosyltransferases involved in carbohydrate synthesis and non-catalytic enzymes involved in complex carbohydrate fractionated metabolism,were lower in the CG group.(3)Metabolite differences and functional analysis resultsA total of 1266 metabolites were identified by cecal metabolomics,and functional enrichment showed significant differences in protein digestion and absorption,sulfur metabolism,sphingolipid signaling pathway,unsaturated fatty acid biosynthesis,and ovarian steroid production between the two groups(P < 0.05),differential metabolites mainly including L-serine,indole,L-tryptophan,arachidonic acid,Eicosapentaenoic acid and 15(S)-Hp ETE.(4)Transcriptome differences and functional analysis resultsTranscriptome sequencing of cecal tissues identified a total of 155 differentially expressed miRNAs and 2153 differentially expressed genes,among which miR-193b-3p,miR-145-5p,miR-283-3p,and miR-423-5p were significantly upregulated in the EG group(P < 0.05),while miR-21-5p and miR-215-5p were significantly upregulated in the CG group(P < 0.05);compared with the EG group,IL1 A,MAP3K11,and S100A9 were significantly upregulated in the CG group(P < 0.05),and the levels of TNF-α,IL-1β,and IL-6 in the CG group were significantly increased(P < 0.05).Functional enrichment was shown to be mainly concentrated in cell adhesion,ECM-receptor interaction,PI3K-Akt signaling pathway,MAPK signaling pathway,and regulatory signaling pathway of cell migration.(5)Results of multi-omics association analysisThe combined analysis of miRNA and mRNA showed that miRNA-targeted mRNA worked,and low-weight rabbits may cause inflammation of the cecum by novel＿124 targeting MAP3K11 and ocu-miR-328-3p by targeting CASP3,thereby affecting the normal growth rate.mRNA is highly correlated with gut microbes or metabolites,such as Mariniblastus with CASP3(P < 0.05)and S100A9 and MAP3K11(P < 0.05);L-serine was significantly positively correlated with CREBBP(P < 0.05),and L-Carnitine was significantly negatively correlated with IL1 A and S100A9(P < 0.05);Eicosapentaenoic acid and testosterone were mainly positively correlated with genera Deinococcus,Kingella,and Prevotella,while pregnenolone,arachidonic acid,and indole tended in the opposite direction.It is hypothesized that changes in these key genes,metabolites,and genes in the cecum influence the occurrence of low-weight cecum inflammation in rabbits.In summary,through integrated analysis of multiple groups,this study found that phylum Verrucomicrobioa,phylum Actinobacteria,L-serine,Arachidonic acid,IL-1A,MAP3K11,S100A9 and miR-21-5p in the CG group were significantly up-regulated;phylum Bacteroidetes,genera Bacteroidetes,Eicosapentaenoic acid,and miR-193b-3p were significantly down-regulated,and the identified candidate microorganisms,metabolites,and genes may promote inflammatory responses and are not conducive to weight gain.This study provides a theoretical basis for exploring the molecular regulatory mechanisms of different body weights in meat rabbits and provides a reference basis for further improving the growth performance of meat rabbits.