Casaro S, Prim J G, Gonzalez T D, Cunha F, Silva A C M, Yu H, 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, 32610, USA.
Department of Clinical Sciences, Auburn University, Auburn, AL, 36849, USA.
Anim Microbiome. 2025 Jan 9;7(1):4. doi: 10.1186/s42523-024-00366-9.
Cows that develop metritis experience dysbiosis of their uterine microbiome, where opportunistic pathogens overtake uterine commensals. An effective immune response is critical for maintaining uterine health. Nonetheless, periparturient cows experience immune dysregulation, which seems to be intensified by prepartum over-condition. Herein, Bayesian networks were applied to investigate the directional correlations between prepartum body weight (BW), BW loss, pre- and postpartum systemic immune profiling and plasma metabolome, and postpartum uterine metabolome and microbiome.
The Bayesian network analysis showed a positive directional correlation between prepartum BW, prepartum BW loss, and plasma fatty acids at parturition, suggesting that heavier cows were in lower energy balance than lighter cows. There was a positive directional correlation between prepartum BW, prepartum systemic leukocyte death, immune activation, systemic inflammation, and metabolomic changes associated with oxidative stress prepartum and at parturition. Immune activation and systemic inflammation were characterized by increased proportion of circulating polymorphonuclear cells (PMN) prepartum, B-cell activation at parturition, interleukin-8 prepartum and at parturition, and interleukin-1β at parturition. These immune changes together with plasma fatty acids at parturition had a positive directional correlation with PMN extravasation postpartum, which had a positive directional correlation with uterine metabolites associated with tissue damage. These results suggest that excessive PMN migration to the uterus leads to excessive endometrial damage. The aforementioned changes had a positive directional correlation with Fusobacterium, Porphyromonas, and Bacteroides in cows that developed metritis, suggesting that excessive tissue damage may disrupt physical barriers or increase substrate availability for bacterial growth.
This work provides robust mechanistic hypotheses for how prepartum BW may impact peripartum immune and metabolic profiles, which may lead to uterine opportunistic pathogens overgrowth and metritis development.
发生子宫炎的奶牛会出现子宫微生物群失调，机会性病原体取代子宫共生菌。有效的免疫反应对于维持子宫健康至关重要。然而，围产期奶牛会经历免疫失调，产前过度肥胖似乎会加剧这种失调。在此，应用贝叶斯网络研究产前体重（BW）、体重减轻、产前和产后全身免疫谱及血浆代谢组，以及产后子宫代谢组和微生物组之间的方向性关联。
贝叶斯网络分析显示，产前BW、产前体重减轻与分娩时血浆脂肪酸之间存在正向关联，表明较重的奶牛能量平衡低于较轻的奶牛。产前BW、产前全身白细胞死亡、免疫激活、全身炎症以及产前和分娩时与氧化应激相关的代谢组学变化之间存在正向关联。免疫激活和全身炎症的特征是产前循环多形核细胞（PMN）比例增加、分娩时B细胞激活、产前和分娩时白细胞介素-8以及分娩时白细胞介素-1β增加。这些免疫变化与分娩时的血浆脂肪酸一起与产后PMN渗出呈正向关联，而PMN渗出与与组织损伤相关的子宫代谢产物呈正向关联。这些结果表明，PMN过度迁移至子宫会导致子宫内膜过度损伤。上述变化与发生子宫炎的奶牛中的梭杆菌属、卟啉单胞菌属和拟杆菌属呈正向关联，表明过度的组织损伤可能会破坏物理屏障或增加细菌生长的底物可用性。
这项工作为产前BW如何影响围产期免疫和代谢谱提供了有力的机制假设，这可能导致子宫机会性病原体过度生长和子宫炎的发生。
