Abstract：
Bovine respiratory disease (BRD) continues to pose a serious threat to the cattle industry, resulting in substantial economic losses. As a multifactorial disease, pathogen infection and respiratory microbial imbalance are important causative factors in the occurrence and development of BRD. Integrative analyses of 16S rRNA sequencing and metabolomics allow comprehensive identification of the changes in microbiota and metabolism associated with BRD, making it possible to determine which pathogens are responsible for the disease and to develop new therapeutic strategies. In our study, 16S rRNA sequencing and metagenomic analysis were used to describe and compare the composition and diversity of nasal microbes in healthy cattle and cattle with BRD from different farms in Yinchuan, Ningxia, China. We found a significant difference in nasal microbial diversity between diseased and healthy bovines; notably, the relative abundance of Mycoplasma bovis and Pasteurella increased. This indicated that the composition of the microbial community had changed in diseased bovines compared with healthy ones. The data also strongly suggested that the reduced relative abundance of probiotics, including Pasteurellales and Lactobacillales, in diseased samples contributes to the susceptibility to bovine respiratory disease. Furthermore, serum metabolomic analysis showed altered concentrations of metabolites in BRD and that a significant decrease in lactic acid and sarcosine may impair the ability of bovines to generate energy and an immune response to pathogenic bacteria. Based on the correlation analysis between microbial diversity and the metabolome, lactic acid (2TMS) was positively correlated with Gammaproteobacteria and Bacilli and negatively correlated with Mollicutes. In summary, microbial communities and serum metabolites in BRD were characterized by integrative analysis. This study provides a reference for monitoring biomarkers of BRD, which will be critical for the prevention and treatment of BRD in the future.
摘要：
牛呼吸道疾病(BRD)继续对养牛业构成严重威胁,造成了巨大的经济损失。作为一种多因素疾病，病原体感染和呼吸道微生物失衡是BRD发生发展的重要原因。16SrRNA测序和代谢组学的综合分析可以全面鉴定与BRD相关的微生物群和代谢变化。这使得有可能确定哪些病原体是造成这种疾病的原因，并开发新的治疗策略。在我们的研究中,采用16SrRNA测序和宏基因组分析对银川市不同养殖场的健康牛和BRD牛鼻腔微生物的组成和多样性进行了描述和比较,宁夏,中国。我们发现患病和健康牛之间的鼻微生物多样性存在显着差异；特别是，牛支原体和巴氏杆菌的相对丰度增加。这表明与健康牛相比，患病牛的微生物群落组成发生了变化。数据还强烈表明，益生菌的相对丰度降低，包括巴氏杆菌和乳杆菌，在患病样品中，对牛呼吸道疾病的易感性有贡献。此外，血清代谢组学分析显示，BRD中代谢物的浓度发生了变化，乳酸和肌氨酸的显着减少可能会损害牛产生能量的能力和对病原菌的免疫反应。基于微生物多样性与代谢组的相关性分析,乳酸（2TMS）与γ变形菌和芽孢杆菌呈正相关，与微藻呈负相关。总之,通过综合分析对BRD中的微生物群落和血清代谢产物进行了表征。本研究为监测BRD的生物标志物提供参考,这对未来BRD的预防和治疗至关重要。
