Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610; D. H. Barron Reproductive and Perinatal Biology Research Program, University of Florida, Gainesville 32610.
Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY 14853.
J Dairy Sci. 2019 Dec;102(12):11786-11797. doi: 10.3168/jds.2019-17106. Epub 2019 Oct 3.
Until 2010, our knowledge of the uterine microbiome in cows that developed uterine disease relied almost exclusively on culture-dependent studies and mostly included cows with clinical endometritis (i.e., with purulent uterine discharge). Those studies consistently found a strong positive correlation between Trueperella pyogenes and clinical endometritis, whereas other pathogens such as Escherichia coli, Fusobacterium necrophorum, Prevotella melaninogenica, and Bacteroides spp. were also commonly cocultured. In contrast, Streptococcus spp., Staphylococcus spp., and Bacillus spp. were usually isolated from healthy cows. Starting in 2010, culture-independent studies using PCR explored the microbiome of cows with metritis and clinical endometritis, and observed that E. coli was a pioneer pathogen that predisposed cows to infection with F. necrophorum, which was strongly associated with metritis, and to infection with T. pyogenes, which was strongly associated with clinical endometritis. Starting in 2011, culture-independent studies using metagenomic sequencing expanded our knowledge of the uterine microbiome. It has been shown that cows have bacteria in the uterus even before calving, they have an established uterine microbiome within 20 min of calving, and that the microbiome structure is identical between cows that develop metritis and healthy cows until 2 d postpartum, after which the bacterial structure of cows that developed metritis deviates in favor of greater relative abundance of Bacteroidetes and Fusobacteria and lesser relative abundance of Proteobacteria and Tenericutes. The shift in the uterine microbiome in cows that develop metritis is characterized by a loss of heterogeneity and a decrease in bacterial richness. At the genus level, Bacteroides, Porphyromonas, and Fusobacterium have the strongest association with metritis. At the species level, we observed that Bacteroides pyogenes, Porphyromonas levii, and Helcococcus ovis were potential emerging uterine pathogens. Finally, we have shown that the hematogenous route is a viable route of uterine infection with uterine pathogens. Herein, we propose that metritis is associated with a dysbiosis of the uterine microbiota characterized by decreased richness, and an increase in Bacteroidetes and Fusobacteria, particularly Bacteroides, Porphyromonas, and Fusobacterium.
直到 2010 年，我们对患有子宫疾病的奶牛子宫微生物组的了解几乎完全依赖于依赖培养的研究，并且这些研究主要集中在患有临床子宫内膜炎（即化脓性子宫分泌物）的奶牛上。这些研究一致发现，化脓真杆菌与临床子宫内膜炎之间存在很强的正相关关系，而其他病原体，如大肠杆菌、坏死梭杆菌、黑色素普雷沃氏菌和拟杆菌属等，也经常共同培养。相比之下，链球菌属、葡萄球菌属和芽孢杆菌属通常从健康奶牛中分离出来。从 2010 年开始，使用 PCR 的非培养研究探索了患有子宫炎和临床子宫内膜炎的奶牛的微生物组，观察到大肠杆菌是一种先驱病原体，使奶牛容易感染坏死梭杆菌，而坏死梭杆菌与子宫炎密切相关，也容易感染化脓真杆菌，而化脓真杆菌与临床子宫内膜炎密切相关。从 2011 年开始，使用宏基因组测序的非培养研究扩展了我们对子宫微生物组的认识。研究表明，奶牛在分娩前的子宫中就已经有细菌，它们在分娩后 20 分钟内就建立了一个稳定的子宫微生物组，并且在分娩后 2 天内，患有子宫炎和健康奶牛的微生物组结构是相同的，之后患有子宫炎的奶牛的细菌结构就会发生变化，有利于厚壁菌门和梭杆菌门的相对丰度增加，变形菌门和无壁菌门的相对丰度减少。患有子宫炎的奶牛的子宫微生物组的变化特征是失去异质性和细菌丰富度降低。在属水平上，拟杆菌属、卟啉单胞菌属和梭杆菌属与子宫炎的关系最强。在种水平上，我们观察到，普通拟杆菌、柔弱普雷沃氏菌和绵羊唾液球菌是潜在的新兴子宫病原体。最后，我们表明，血源性途径是一种可行的子宫感染途径，与子宫病原体有关。在这里，我们提出，子宫炎与子宫微生物组的失调有关，其特征是丰富度降低，厚壁菌门和梭杆菌门增加，特别是拟杆菌属、卟啉单胞菌属和梭杆菌属。
