摘要The rumen is an important organ that enables ruminants to digest nutrients.However,the biological mechanism by which the microbiota and its derived fatty acids regulate rumen development is still unclear.In this study,18 female Haimen goats were selected and slaughtered at d 30,60,and 90 of age.Multi-omics analyses(rumen microbial sequencing,host transcriptome sequencing,and rumen epithelial metabolomics)were performed to investigate host-microbe interactions from preweaning to postweaning in a goat model.With increasing age,and after the introduction of solid feed,the increased abundances of Prevotella and Roseburia showed positive correlations with volatile fatty acid(VFA)levels and morphological parameters(P＜0.05).Epithelial transcriptomic analysis showed that the expression levels of hub genes,including 3-hydroxy-3-methylglutaryl-CoA synthase isoform 2(HMGCS2),enoyl-CoA hydratase,short chain 1(ECHS1),and peroxisome proliferator activated receptor gamma(PPARG),were positively associated with animal phenotype(P＜0.05).These hub genes were mainly correlated to VFA metabolism,oxidative phosphorylation,and the mammalian target of rapamycin(mTOR)and peroxi-some proliferator activated receptor(PPAR)signaling pathways(P＜0.05).Moreover,the primary me-tabolites in the epithelium changed from glucose preweaning to(R)-3-hydroxybutyric acid(BHBA)and acetoacetic acid(ACAC)postweaning(P＜0.05).Diet and butyrate were the major factors shaping epithelial metabolomics in young ruminants(P＜0.05).Multi-omics analysis showed that the rumen microbiota and VFA were mainly associated with the epithelial transcriptome,and that alterations in gene expression influenced host metabolism.The"butanoate metabolism"pathway,which tran-scriptomic and metabolomic analyses identified as being upregulated with age,produces ketones that regulate the"oxidative phosphorylation"pathway,which could provide energy for the development of rumen papillae.Our findings reveal the changes that occur in the rumen microbiota,host transcriptome,and metabolome with age,and validate the role of microbiota-derived VFA in manipulating host gene expression and subsequent metabolism.This study provides insight into the molecular mechanisms of host-microbe interactions in goats and supplies a theoretical basis and guidance for precise nutritional regulation during the critical time window for rumen development of young ruminants.