The objectives of this experiment were to determine the effects of supplementing 25-hydroxyvitamin D3 (calcidiol, CAL) compared with vitamin D3 (cholecalciferol, CHOL) at 1 or 3 mg/d in late gestation on production outcomes of dairy cows. One hundred thirty-three parous and 44 nulliparous pregnant Holstein cows were enrolled in the experiment. Cows were blocked by parity and previous lactation milk yield (parous) or genetic merit (nulliparous) and assigned randomly to receive 1 or 3 mg/d of CAL or CHOL in a 2 × 2 factorial arrangement of treatments (CAL1, CAL3, CHOL1, and CHOL3). Treatments were provided to individual cows as a top-dress to the prepartum diet from 250 d in gestation until parturition. The prepartum diet had a dietary cation-anion difference of −128 mEq/kg of dry matter. Production and disease were evaluated for the first 42 d in milk, and reproduction was evaluated to 300 d in milk. Incidence of postpartum diseases did not differ among treatments. Feeding CAL compared with CHOL increased yields of colostrum and colostrum fat, protein, and total solids, resulting in an increased amount of net energy for lactation secreted as colostrum (CHOL = 7.0 vs. CAL = 9.0 ± 0.7 Mcal). An interaction between source and amount was observed for milk yield: CAL3 increased milk yield compared with CHOL3 (CHOL3 = 34.1 vs. CAL3 = 38.7 ± 1.4 kg/d) but milk yield did not differ between CAL1 and CHOL1 (CHOL1 = 36.9 vs. CAL1 = 36.4 ± 1.4 kg/d). Concentrations of serum calcidiol on day of calving and average serum Ca from d 2 to 11 postpartum were positively associated with milk yield in the first 42 d in milk. Interactions between source and amount of vitamin D were also observed for pregnancy after first AI: the percentage of cows receiving CHOL1 and CAL3 that became pregnant was smaller than that of cows receiving CHOL3 and CAL1. However, pregnancy per AI and pregnancy by 300 d in milk did not differ among treatments. Overall, CAL3 increased milk yield compared with CHOL3, whereas in cows fed 1 mg/d (CAL1 and CHOL1), the source of vitamin D generally had no effect. The effect of CAL3 may be explained in part by serum CAL concentrations and postpartum serum Ca, which were associated with milk yield.
Abstract Background 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. Results 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. Conclusions 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.
Abstract Background Cows that develop metritis experience dysbiosis of their uterine microbiome, where opportunistic pathogens overtake uterine commensals. Whether opportunistic pathogens thrive and cause metritis may be determined by how efficiently the immune system responds to these pathogens. Nonetheless, periparturient cows experience immune dysregulation, which seems to be intensified by prepartum obesity and lipid mobilization 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. Results According to the directionality network, greater prepartum BW led to greater BW loss, which led to an increase in plasma fatty acids at parturition, indicating that heavier cows were in lower energy balance than lighter cows. Greater prepartum BW also led to an increase in prepartum systemic cellular death, which led to an increase in systemic inflammation, immune activation, and metabolomic changes associated with oxidative stress prepartum and at parturition, which indicates a positive directional correlation between BW and systemic inflammation. These changes led to an increase in polymorphonuclear cell extravasation postpartum, which led to an increase in uterine metabolomic changes associated with tissue damage, suggesting that excessive polymorphonuclear cell migration to the uterus leads to excessive endometrial damage. These changes led to an increase in pathogenic bacteria in cows that developed metritis, suggesting that excessive tissue damage may disrupt physical barriers or increase substrate availability for bacterial growth. Conclusions This work provides robust mechanistic hypotheses for how prepartum body weight impacts peripartum immune and metabolic profiles, leading to uterine opportunistic pathogens overgrowth and metritis development.