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 peroxisome proliferator activated receptor (PPAR) signaling pathways (P < 0.05). Moreover, the primary metabolites 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 transcriptomic 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.

中文翻译：

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山羊模型中瘤胃上皮细胞中的丁酸盐代谢受宿主和饮食制度的影响


瘤胃是使反刍动物能够消化营养物质的重要器官。然而，微生物群及其衍生脂肪酸调节瘤胃发育的生物学机制仍不清楚。本研究选取 18 只雌性海门山羊，分别在 30 岁、 60 岁和 90 岁时屠宰。进行多组学分析 （瘤胃微生物测序、宿主转录组测序和瘤胃上皮代谢组学） 以研究山羊模型中从断奶前到断奶后的宿主-微生物相互作用。随着年龄的增长，以及引入固体饲料后，Prevotella 和 Roseburia 丰度的增加与挥发性脂肪酸 （VFA） 水平和形态学参数呈正相关 （P < 0.05）。上皮转录组学分析显示，3-羟基-3-甲基戊二酰辅酶A合酶亚型2（HMGCS2）、烯酰辅酶A水合酶短链1（ECHS1）和过氧化物酶体增殖物激活受体γ（PPARG）等枢纽基因的表达水平与动物表型呈正相关（P < 0.05）。这些枢纽基因主要与 VFA 代谢、氧化磷酸化以及哺乳动物雷帕霉素靶标 （mTOR） 和过氧化物酶体增殖物激活受体 （PPAR） 信号通路相关 （P < 0.05）。此外，断奶后上皮中的主要代谢产物从葡萄糖变为 （R）-3-羟基丁酸 （BHBA） 和乙酰乙酸 （ACAC） （P < 0.05）。饮食和丁酸盐是影响年轻反刍动物上皮代谢组学的主要因素 （P < 0.05）。多组学分析表明，瘤胃菌群和 VFA 主要与上皮转录组相关，基因表达的改变影响宿主代谢。 转录组学和代谢组学分析确定的“丁酸代谢”途径随着年龄的增长而上调，产生的酮体调节“氧化磷酸化”途径，可以为瘤胃的发育提供能量。我们的研究结果揭示了瘤胃微生物群、宿主转录组和代谢组随年龄增长而发生的变化，并验证了微生物群衍生的 VFA 在操纵宿主基因表达和随后代谢中的作用。本研究为山羊体内宿主-微生物相互作用的分子机制提供了见解，并为在年轻反刍动物瘤胃发育的关键时间窗口内进行精确的营养调节提供了理论基础和指导。