Casaro S, Prim J G, Gonzalez T D, Cunha F, Bisinotto R S, Chebel R C, Santos J E P, Nelson C D, Jeon S J, Bicalho R C, Driver J P, Galvão Klibs N
Department of Large Animal Clinical Sciences, University of Florida, Gainesville, FL, USA.
Department of Clinical Sciences, Auburn University, Auburn, AL, USA.
Anim Microbiome. 2024 May 27;6(1):30. doi: 10.1186/s42523-024-00314-7.
Metritis is a prevalent uterine disease that affects the welfare, fertility, and survival of dairy cows. The uterine microbiome from cows that develop metritis and those that remain healthy do not differ from calving until 2 days postpartum, after which there is a dysbiosis of the uterine microbiome characterized by a shift towards opportunistic pathogens such as Fusobacteriota and Bacteroidota. Whether these opportunistic pathogens proliferate and overtake the uterine commensals could be determined by the type of substrates present in the uterus. The objective of this study was to integrate uterine microbiome and metabolome data to advance the understanding of the uterine environment in dairy cows that develop metritis. Holstein cows (n = 104) had uterine fluid collected at calving and at the day of metritis diagnosis. Cows with metritis (n = 52) were paired with cows without metritis (n = 52) based on days after calving. First, the uterine microbiome and metabolome were evaluated individually, and then integrated using network analyses.
The uterine microbiome did not differ at calving but differed on the day of metritis diagnosis between cows with and without metritis. The uterine metabolome differed both at calving and on the day of metritis diagnosis between cows that did and did not develop metritis. Omics integration was performed between 6 significant bacteria genera and 153 significant metabolites on the day of metritis diagnosis. Integration was not performed at calving because there were no significant differences in the uterine microbiome. A total of 3 bacteria genera (i.e. Fusobacterium, Porphyromonas, and Bacteroides) were strongly correlated with 49 metabolites on the day of metritis diagnosis. Seven of the significant metabolites at calving were among the 49 metabolites strongly correlated with opportunistic pathogenic bacteria on the day of metritis diagnosis. The main metabolites have been associated with attenuation of biofilm formation by commensal bacteria, opportunistic pathogenic bacteria overgrowth, tissue damage and inflammation, immune evasion, and immune dysregulation.
The data integration presented herein helps advance the understanding of the uterine environment in dairy cows with metritis. The identified metabolites may provide a competitive advantage to the main uterine pathogens Fusobacterium, Porphyromonas and Bacteroides, and may be promising targets for future interventions aiming to reduce opportunistic pathogenic bacteria growth in the uterus.
子宫内膜炎是一种常见的子宫疾病，会影响奶牛的健康、繁殖能力和存活率。患子宫内膜炎的奶牛和保持健康的奶牛的子宫微生物群在产后2天内直至产犊时并无差异，但在此之后，子宫微生物群会出现生态失调，其特征是向诸如梭杆菌门和拟杆菌门等机会性病原体转变。这些机会性病原体是否会增殖并取代子宫共生菌可能取决于子宫中存在的底物类型。本研究的目的是整合子宫微生物群和代谢组数据，以加深对患子宫内膜炎的奶牛子宫环境的理解。对104头荷斯坦奶牛在产犊时和子宫内膜炎诊断日采集子宫液。根据产后天数，将患子宫内膜炎的奶牛（n = 52）与未患子宫内膜炎的奶牛（n = 52）配对。首先，分别评估子宫微生物群和代谢组，然后使用网络分析进行整合。
子宫微生物群在产犊时并无差异，但在子宫内膜炎诊断日，患子宫内膜炎和未患子宫内膜炎的奶牛之间存在差异。在产犊时以及在子宫内膜炎诊断日，患子宫内膜炎和未患子宫内膜炎的奶牛的子宫代谢组均存在差异。在子宫内膜炎诊断日，对6个重要细菌属和153种重要代谢物进行了组学整合。在产犊时未进行整合，因为子宫微生物群没有显著差异。在子宫内膜炎诊断日，共有3个细菌属（即梭杆菌属、卟啉单胞菌属和拟杆菌属）与49种代谢物密切相关。产犊时的7种重要代谢物在子宫内膜炎诊断日与机会性病原体细菌密切相关的49种代谢物之中。主要代谢物与共生菌生物膜形成的减弱、机会性病原体的过度生长、组织损伤和炎症、免疫逃避及免疫失调有关。
本文提出的数据整合有助于加深对患子宫内膜炎的奶牛子宫环境的理解。所鉴定出的代谢物可能为子宫主要病原体梭杆菌属、卟啉单胞菌属和拟杆菌属提供竞争优势，并且可能是未来旨在减少子宫中机会性病原体生长的干预措施的有前景的靶点。
