BACKGROUND Recently, we reported that some dairy cows could produce high amounts of milk with high amounts of protein (defined as milk protein yield [MPY]) when a population was raised under the same nutritional and management condition, a potential new trait that can be used to increase high-quality milk production. It is unknown to what extent the rumen microbiome and its metabolites, as well as the host metabolism, contribute to MPY. Here, analysis of rumen metagenomics and metabolomics, together with serum metabolomics was performed to identify potential regulatory mechanisms of MPY at both the rumen microbiome and host levels. RESULTS Metagenomics analysis revealed that several Prevotella species were significantly more abundant in the rumen of high-MPY cows, contributing to improved functions related to branched-chain amino acid biosynthesis. In addition, the rumen microbiome of high-MPY cows had lower relative abundances of organisms with methanogen and methanogenesis functions, suggesting that these cows may produce less methane. Metabolomics analysis revealed that the relative concentrations of rumen microbial metabolites (mainly amino acids, carboxylic acids, and fatty acids) and the absolute concentrations of volatile fatty acids were higher in the high-MPY cows. By associating the rumen microbiome with the rumen metabolome, we found that specific microbial taxa (mainly Prevotella species) were positively correlated with ruminal microbial metabolites, including the amino acids and carbohydrates involved in glutathione, phenylalanine, starch, sucrose, and galactose metabolism. To detect the interactions between the rumen microbiome and host metabolism, we associated the rumen microbiome with the host serum metabolome and found that Prevotella species may affect the host's metabolism of amino acids (including glycine, serine, threonine, alanine, aspartate, glutamate, cysteine, and methionine). Further analysis using the linear mixed effect model estimated contributions to the variation in MPY based on different omics and revealed that the rumen microbial composition, functions, and metabolites, and the serum metabolites contributed 17.81, 21.56, 29.76, and 26.78%, respectively, to the host MPY. CONCLUSIONS These findings provide a fundamental understanding of how the microbiome-dependent and host-dependent mechanisms contribute to varied individualized performance in the milk production quality of dairy cows under the same management condition. This fundamental information is vital for the development of potential manipulation strategies to improve milk quality and production through precision feeding. Video Abstract.

中文翻译：

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多组学研究表明，瘤胃微生物组及其代谢组以及宿主代谢组有助于个体化奶牛的生产。

背景技术最近，我们报道了一些奶牛在相同的营养和管理条件下饲养时可以产生大量具有高蛋白的牛奶（定义为牛奶蛋白产量[MPY]），这可能是一种潜在的新特性。用于增加优质牛奶的产量。尚不清楚瘤胃微生物组及其代谢产物以及宿主代谢在多大程度上影响了MPY。在这里，对瘤胃宏基因组学和代谢组学以及血清代谢组学进行分析，以确定瘤胃微生物组和宿主水平上MPY的潜在调控机制。结果元基因组学分析表明，高MPY奶牛瘤胃中的几种Prevotella物种明显丰富，有助于改善与支链氨基酸生物合成有关的功能。此外，高MPY奶牛的瘤胃微生物组具有产甲烷和产甲烷功能的生物体的相对丰度较低，表明这些奶牛可能产生较少的甲烷。代谢组学分析表明，高MPY奶牛的瘤胃微生物代谢产物（主要是氨基酸，羧酸和脂肪酸）的相对浓度和挥发性脂肪酸的绝对浓度较高。通过将瘤胃微生物组与瘤胃代谢组相关联，我们发现特定的微生物分类群（主要是Prevotella菌种）与瘤胃微生物代谢产物呈正相关，包括谷胱甘肽，苯丙氨酸，淀粉，蔗糖和半乳糖代谢涉及的氨基酸和碳水化合物。为了检测瘤胃微生物组与宿主代谢之间的相互作用，我们将瘤胃微生物组与宿主血清代谢组相关联，发现普氏杆菌可能影响宿主的氨基酸代谢（包括甘氨酸，丝氨酸，苏氨酸，丙氨酸，天冬氨酸，谷氨酸，半胱氨酸）和蛋氨酸）。使用线性混合效应模型进行的进一步分析基于不同的组学方法估计了MPY变异的贡献，并发现瘤胃微生物组成，功能和代谢产物以及血清代谢产物分别对MPY的贡献为17.81、21.56、29.76和26.78％。主机MPY。结论这些发现为在相同管理条件下微生物组依赖性和宿主依赖性机制如何促进奶牛产奶质量的不同个性化表现提供了基本理解。这些基本信息对于开发潜在的操纵策略以通过精确进料提高牛奶质量和产量至关重要。录像摘要。