Periparturient diseases of dairy cows are caused by disproportionate energy metabolism, mineral imbalance, and perturbed immune function. The aim of the present study was to characterize metabolism, innate immune endometrial gene expression, and uterine microbial populations of transition animals receiving normal or restricted energy diets. Pregnant multiparous Holstein cows (n = 14) were randomly assigned to one of the two dietary treatments from 20 d prepartum until 35 d postpartum (DPP). One group was fed a diet providing 100% energy requirements (NE), whereas the other received an energy-restricted diet providing 80% energy requirements (RE). Feed intake, milk yield, body weight, body condition score, temperature, respiratory, and pulse rate were recorded. After calving, blood was collected weekly to analyze nonesterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and total cholesterol (TC). Endometrial cytobrushes were collected for gene expression analysis of inflammatory markers, microbial populations determination, and cytological evaluation. The restricted energy diet did not alter feed intake or milk yield but changed energy balance and metabolites levels (P < 0.05). In fact, RE animals had high NEFA and BHB levels, and low TC concentrations (P < 0.05). Moreover, RE animals had upregulated gene expression of serum amyloid A3 (SAA3) at 35 DPP (P < 0.05) and CXC chemokine receptor 2 (CXCR2) at 14 DPP (P < 0.01). Interleukin (IL) 1 and IL8 genes were downregulated 14 DPP but upregulated 35 DPP in RE animals, whereas IL6 and lipopolysaccharide-binding protein (LBP) genes were upregulated at 14 DPP (P ≤ 0.05). The most abundant phyla in RE animals (n = 3) were Bacteroidetes and Fusobacteria, whereas Proteobacteria was the least abundant at both 14 and 35 DPP. In conclusion, it can be speculated that energy balance is one of the main drivers for uterine inflammation by affecting metabolism, immune function, and uterine microbiota. However, these findings should be validated in a larger sample size.
