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Recent research on the transition period (TP) of dairy cows has highlighted the pivotal role of immune function in affecting the severity of metabolic challenges the animals face when approaching calving. This suggests that the immune system may play a role in the etiology of metabolic diseases occurring in early lactation. Several studies have indicated that the roots of immune dysfunctions could sink way before the “classical” TP (e.g., 3 weeks before and 3 weeks after calving), extending the time frame deemed as “risky” for the development of early lactation disorders at the period around the dry-off. Several distressing events occurring during the TP (i.e., dietary changes, heat stress) can boost the severity of pre-existing immune dysfunctions and metabolic changes that physiologically affect this phase of the lactation cycle, further increasing the likelihood of developing diseases. Based on this background, several operational and nutritional strategies could be adopted to minimize the detrimental effects of immune dysfunctions on the adaptation of dairy cows to the new lactation. A suitable environment (i.e., optimal welfare) and a balanced diet (which guarantees optimal nutrient partitioning to improve immune functions in cow and calf) are key aspects to consider when aiming to minimize TP challenges at the herd level. Furthermore, several prognostic behavioral and physiological indicators could help in identifying subjects that are more likely to undergo a “bad transition”, allowing prompt intervention through specific modulatory treatments. Recent genomic advances in understanding the linkage between metabolic disorders and the genotype of dairy cows suggest that genetic breeding programs aimed at improving dairy cows’ adaptation to the new lactation challenges (i.e., through increasing immune system efficiency or resilience against metabolic disorders) could be expected in the future. Despite these encouraging steps forward in understanding the physiological mechanisms driving metabolic responses of dairy cows during their transition to calving, it is evident that these processes still require further investigation, and that the TP—likely extended from dry-off—continues to be “the final frontier” for research in dairy sciences.

The scope of this experiment was to study the effects of Saccharomyces cerevisiae fermentation product (SCFP; NutriTek, Diamond V) on milk yield, milk composition, somatic cell count, rumination activity, and immunometabolic profile (inflammation) of dairy cows during the peripartum period. Postpartum inflammation severity was evaluated as the liver functionality index (LFI). The LFI is based on profiles of specific blood inflammatory markers in the first month of lactation. We hypothesized that SCFP could increase the rumination time in dairy cows. Treatments were control (CTR; no supplement, n = 17) or SCFP (19 g/d of NutriTek, n = 17) included into a pellet delivered at robotic milking unit. Treatments were fed from d -60 to 42 relative to parturition. Cows were fed the same basal rations formulated to pre- or postpartum requirements. Cows were voluntarily milked with robotic milking unit. Blood samples were collected at d -60, -28, -7, 7, and 28 relative to parturition. To study the effect of the treatment and severity of inflammation during periparturient period on subsequent cow performance, cows were retrospectively divided into 2 groups based on their LFI score: low (LLFI) and high (HLFI). Thus, LFI grouping and supplementation treatment groups were as follows: LLFI-CTR, LLFI-SCFP, HLFI-CTR, HLFI-SCFP. Data were analyzed with ANOVA using a mixed model for repeated measures; the model included the effect of the diet, LFI group, time relative to parturition, and their interaction. The nonesterified fatty acids concentrations were greatest at d 7 of lactation for LLFI-CTR compared with other groups. No other differences in plasma metabolites were observed. The LLFI-CTR cows had a greater reduction of body condition score from d -7 until 28 relative to parturition compared with other groups. Somatic cell counts were not different among groups, with averages of 175, 169, 384, and 126 × 1,000 cells/mL for the HLFI-CTR, HLFI-SCFP, LLFI-CTR, and LLFI-SCFP group, respectively, regardless of day. However, the LLFI-CTR had greater somatic cell count on d 42 compared with other groups. During the week before parturition, the LLFI-CTR group had reduced rumination time of 46 min compared with the other 3 groups. However, the minutes of rumination per day was only different between LLFI-CTR and the LLFI-SCFP groups. Milk production of cows was different for LFI scores as follows: 50.2 versus 46.7 kg/d for HLFI and LLFI, respectively. Interestingly, there were no differences of milk production due to supplementation treatment of the HLFI cows. However, the LLFI-SCFP group produced 49.1 kg/d compared with 44.3 kg/d of the LLFI-CTR group during the first month of lactation. Milk composition did not differ throughout the experimental period for the 4 groups of cows. In conclusion, SCFP supplementation assisted cows experiencing low LFI to maintain milk production, somatic cell count, and plasma nonesterified fatty acid concentrations similar to cows with high LFI.

Feeding yeast culture fermentation products has been associated with improved feed intake and milk yield in transition dairy cows. These improvements in performance have been further described in terms of rumen characteristics, metabolic profile, and immune response. The objective of this study was to evaluate the effects of a commercial yeast culture product (YC; Culture Classic HD, Phibro Animal Health) on performance, blood biomarkers, rumen fermentation, and rumen bacterial population in dairy cows from -30 to 50 d in milk (DIM). Forty Holstein dairy cows were enrolled in a randomized complete block design from -30 to 50 DIM and blocked according to expected calving day, parity, previous milk yield, and genetic merit. At -30 DIM, cows were assigned to either a basal diet plus 114 g/d of ground corn (control; n = 20) or a basal diet plus 100 g/d of ground corn and 14 g/d of YC (n = 20), fed as a top-dress. Cows received the same close-up diet from 30 d prepartum until calving [1.39 Mcal/kg of dry matter (DM) and 12.3% crude protein (CP)] and lactation diet from calving to 50 DIM (1.60 Mcal/kg of DM and 15.6% CP). Blood samples and rumen fluid were collected at various time points from -30 to 50 d relative to calving. Cows fed YC compared with control showed a trend for increased energy-corrected milk (+3.2 kg/d). Lower somatic cell counts were observed in YC cows than in control. We detected a treatment × time interaction in nonesterified fatty acids (NEFA) that could be attributed to a trend for greater NEFA in YC cows than control at 7 DIM, followed by lower NEFA in YC cows than control at 14 and 30 DIM. In the rumen, YC contributed to mild changes in rumen fermentation, mainly increasing postpartal valerate while decreasing prepartal isovalerate. This was accompanied by alterations in rumen microbiota, including a greater abundance of cellulolytic (Fibrobacter succinogenes) and lactate-utilizing bacteria (Megasphaera elsdenii). These results describe the potential benefits of supplementing yeast culture during the late pregnancy through early lactation, at least in terms of rumen environment and performance.

The aim of this study was to investigate the associations between differential somatic cell count (DSCC) and milk quality and udder health traits, and for the first time, between DSCC and milk coagulation properties and cheesemaking traits in a population of 1,264 Holstein cows reared in northern Italy. Differential somatic cell count represents the combined proportions of polymorphonuclear neutrophils plus lymphocytes (PMN-LYM) in the total somatic cell count (SCC), with macrophages (MAC) making up the remaining proportion. The milk traits investigated in this study were milk yield (MY), 8 traits related to milk composition and quality (fat, protein, casein, casein index, lactose, urea, pH, and milk conductivity), 9 milk coagulation traits [3 milk coagulation properties (MCP) and 6 curd firming (CF) traits], 7 cheesemaking traits, 3 cheese yield (CY) traits, and 4 milk nutrient recovery in the curd (REC) traits. A linear mixed model was fitted to explore the associations between SCS combined with DSCC and the aforementioned milk traits. An additional model was run, which included DSCC expressed as the PMN-LYM and MAC counts, obtained by multiplying the percentage of PMN-LYM and MAC by SCC in the milk for each cow in the data set. The unfavorable association between SCS and milk quality and technological traits was confirmed. Increased DSCC was instead associated with a linear increase in MY, casein index, and lactose proportion and a linear decrease in milk fat and milk conductivity. Accordingly, DSCC was favorably associated with all MCP and CF traits (with the exception of the time needed to achieve maximum, CF), particularly with rennet coagulation time, and it always displayed linear relationships. Differential somatic cell count was also positively associated with the recovery of milk nutrients in the curd (protein, fat, and energy), which increased linearly with increasing DSCC. The PMN-LYM count was rarely associated with milk traits, even though the pattern observed confirmed the results obtained when both SCS and DSCC were included in the model. The MAC count, however, showed the opposite pattern: MY, casein index, and lactose percentage decreased and milk conductivity increased with an increasing MAC count. No significant association was found between PMN-LYM count and MCP, CF, CY, and REC traits, whereas MAC count was unfavorably associated with MCP, CF traits, some CY traits, and all REC traits. Our results showed that the combined information derived from SCS and DSCC might be useful to monitor milk quality and cheesemaking-related traits.

The objective of this study was to evaluate whether dairy sheep during the transition period are affected by their parity numbers with regard to (1) body weight (BW), body condition score (BCS), and production performance (milk yield and composition) and (2) metabolic, inflammation, and stress biomarkers. For this purpose, 30 Sarda dairy ewes [15 primiparous (PRP) and 15 multiparous (MUP) ewes] were recruited on d 90 of gestation. Each group was homogeneous according to age, BW, and BCS. Sampling was carried out at -60, -30, -7, 0, +30, and +60 d from lambing. The MUP ewes showed a higher BW (46.32 vs. 38.71 kg) and larger litter size (1.45 vs. 1.06 kg) but a lower BCS (2.47 vs. 2.70) than the PRP ewes. Furthermore, the MUP ewes had lower concentrations of glucose (3.49 vs. 4.27 mol/L), cholesterol (1.63 vs. 1.81 mmol/L), free fatty acids (0.47 vs. 0.62 mmol/L), and triglycerides (0.22 vs. 0.25 mmol/L) compared with PRP ewes. With regard to inflammation and oxidative stress parameters, the PRP group had higher haptoglobin (0.48 vs. 0.18 g/L) and paraoxonase (187.90 vs. 152.11 U/L) activity than the MUP group. Overall, the MUP ewes were characterized by greater milk production performance and greater feed intake, resulting in a better energy balance, than the PRP ewes. Interestingly, these findings highlighted a different metabolic and inflammatory response over the transition period between PRP and MUP ewes, with the latter displaying lower concentrations of inflammatory-related biomarkers.

The transition period of dairy cattle is characterized by a number of metabolic, endocrine, physiologic, and immune adaptations, including the occurrence of negative energy balance, hypocalcemia, liver dysfunction, overt systemic inflammatory response, and oxidative stress status. The degree and length of time during which these systems remain out of balance could render cows more susceptible to disease, poor reproductive outcomes, and less efficient for milk production and quality. Studies on both monogastrics and ruminants have reported the health benefits of nutraceuticals (e.g. probiotics, prebiotics, dietary lipids, functional peptides, phytoextracts) beyond nutritional value, interacting at different levels of the animal’s physiology. From a physiological standpoint, it seems unrealistic to disregard any systemic inflammatory processes. However, an alternate approach is to modulate the inflammatory process per se and to resolve the systemic response as quickly as possible.To this aim, a growing body of literature underscores the efficacy of nutraceuticals (active compounds) during the critical phase of the transition period. Supplementation of essential fatty acids throughout a 2-month period (i.e. a month before and a month after calving) successfully attenuates the inflammatory status with a quicker resolution of phenomenon. In this context, the inflammatory and immune response scenario has been recognized to be targeted by the beneficial effect of methyl donors, such as methionine and choline, directly and indirectly modulating such response with the increase of antioxidants GSH and taurine. Indirectly by the establishment of a healthy gastrointestinal tract, yeast and yeast-based products showed to modulate the immune response, mitigating negative effects associated with parturition stress and consequent disorders.The use of phytoproducts has garnered high interest because of their wide range of actions on multiple tissue targets encompassing a series of antimicrobial, antiviral, antioxidant, immune-stimulating, rumen fermentation, and microbial modulation effects. In this review, we provide perspectives on investigations of regulating the immune responses and metabolism using several nutraceuticals in the periparturient cow.

[EN] Dairy cows with high body condition score (BCS) in late prepartum are more susceptible to oxidative stress (OS). Nuclear factor erythroid 2-like 2 (NFE2L2) is a major antioxidant transcription factor. We investigated the effect of precalving BCS on blood biomarkers associated with OS, inflammation, and liver function, along with mRNA and protein abundance of targets related to NFE2L2 and glutathione (GSH) metabolism in s.c. adipose tissue (SAT) of periparturient dairy cows. Twenty-two multiparous Holstein cows were retrospectively classified into a high BCS (HBCS; n = 11, BCS ¿3.5) or normal BCS (NBCS; n = 11, BCS ¿3.17) on d 28 before parturition. Cows were fed a corn silage- and wheat straw-based total mixed ration during late prepartum, and a corn silage- and alfalfa hay-based total mixed ration postpartum. Blood samples obtained at ¿10, 7, 15, and 30 d relative to parturition were used for analyses of biomarkers associated with inflammation, including albumin, ceruloplasmin, haptoglobin, and myeloperoxidase, as well as OS, including ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), and ß-carotene. Adipose biopsies harvested at ¿15, 7, and 30 d relative to parturition were analyzed for mRNA (real-time quantitative PCR) and protein abundance (Western blotting) of targets associated with the antioxidant transcription regulator nuclear factor, NFE2L2, and GSH metabolism pathway. In addition, concentrations of GSH, ROS and malondialdehyde were measured. High BCS cows had lower prepartum dry matter intake expressed as a percentage of body weight along with greater BCS loss between ¿4 and 4 wk relative to parturition. Plasma concentrations of ROS and FRAP increased after parturition regardless of treatment. Compared with NBCS, HBCS cows had greater concentrations of FRAP at d 7 postpartum, which coincided with peak values in those cows. In addition, NBCS cows experienced a marked decrease in plasma ROS after d 7 postpartum, while HBCS cows maintained a constant concentration by d 30 postpartum. Overall, ROS concentrations in SAT were greater in HBCS cows. However, overall mRNA abundance of NFE2L2 was lower and cullin 3 (CUL3), a negative regulator of NFE2L2, was greater in HBCS cows. Although HBCS cows had greater overall total protein abundance of NFE2L2 in SAT, ratio of phosphorylated NFE2L2 to total NFE2L2 was lower, suggesting a decrease in the activity of this antioxidant system. Overall, mRNA abundance of the GSH metabolism-related genes glutathione reductase (GSR), glutathione peroxidase 1 (GPX1), and transaldolase 1 (TALDO1), along with protein abundance of glutathione S-transferase mu 1 (GSTM1), were greater in HBCS cows. Data suggest that HBCS cows might experience greater systemic OS after parturition, while increased abundance of mRNA and protein components of the GSH metabolism pathway in SAT might help alleviate tissue oxidant status. Data underscored the importance of antioxidant mechanisms at the tissue level. Thus, targeting these pathways in SAT during the periparturient period via nutrition might help control tissue remodeling while allowing optimal performance., Y. Liang is a recipient of a doctoral fellowship from China Scholarship Council (CSC, Beijing, China). A. S. Alharthi received a fellowship from King Saud University to perform his PhD studies at the University of Illinois (Urbana). A. A. Elolimy was recipient of a fellowship from Higher Education Ministry, Egypt to perform his Ph.D. studies at the University of Illinois (Urbana). We thank Perdue AgriBusiness (Salisbury, MD) for the donation of ProvAAL2 AADvantage during the course of the experiment. The authors have not stated any conflicts of interest.

Some pasture species are rich in phytochemicals, able to improve milk yield and quality and to reduce the environmental impacts of livestock farming. The phytochemicals interact with the different gene networks within the animal, such as nuclear factor erythroid 2-related factor 2 (NRF2), but their overall impact on animal health remains to be fully understood. The objective of this study was to identify the effects of pasture Legumes and non-leguminous Forbs containing high bioactive compounds on metabolism and activity of the liver, antioxidant response, kidney function, and inflammation of dairy cows using a large array of blood parameters associated with metabolism and the innate immune system. For this purpose, 26 parameters and the concentration of certain bioactive compounds were assessed in blood plasma, collected from the Jersey cows grazing either Grass, Legume, or Forb-based pastures. In addition, serum collected from all the cows was utilized to detect the changes in NRF2 activation in bovine mammary alveolar cells (MACT) and hepatocytes. Compared with Grass, the cows that grazed both Forb and Legume pastures had lower β-hydroxybutyric acid (BHB) and creatinine and larger vitamin E and the ferric reducing ability of the plasma, supporting an improved antioxidative status for these animals. Compared with both Grass and Legume, the cows that graze Forb pasture had lower urea and urea to creatinine ratio, and lower creatinine, indicating a better kidney function. The cows grazing Legume pasture had greater hematocrit, bilirubin, cholesterol, albumin, β-carotene, retinol, and thiol groups but lower ceruloplasmin, paraoxonase, and myeloperoxidase (MPO) than those grazed Grass and Forb pastures, indicating a positive effect of Legume pasture on the liver, oxidative stress, and red blood cells. The plasma of cows in the various pastures was enriched with various isoflavonoids, especially the cows grazed on Forb and Legume pastures, which likely contributed to improving the antioxidative status of those cows. However, this effect was likely not due to the higher activation of NRF2. Overall, these results indicate that Forb and Legume pastures rich in secondary metabolites do not strongly affect the metabolism but can improve the status of the liver and the kidney and improve the efficiency of N utilization and antioxidant response, compared with the Grass pasture.

The objective of the present study was to evaluate the effects of an antioxidant and anti-inflammatory compound found in rosemary plants (Salvia rosmarinus) named carnosic acid during the transition period of dairy cows. From day 1 to 3 after calving, 16 multiparous Holstein cows received a daily intravenous infusion of either 500 mL of saline (NaCl 0.9%, Saline, n = 8) or carnosic acid at a rate of 0.3 mg/kg of BW supplied in 500 mL of saline (CA, n = 8). Blood samples were taken at –7, 2, 5, 7, 14, and 21 d relative to parturition, then analyzed for metabolites related to energy metabolism, muscle mass catabolism, liver function, inflammation, and oxidative stress. CA infusion tended to improve milk performance, however, DMI was unaffected by treatment. At 2 d relative to parturition, CA cows had lower blood concentrations of haptoglobin, paraoxonase, FRAP, and NO2– than saline cows. After treatment infusions, haptoglobin remained lower in CA cows than saline at 5 d relative to parturition. Our results demonstrate that carnosic acid promoted positive responses on inflammation and oxidative stress biomarkers and may promote beneficial effects on lactation performance in peripartal dairy cows.

The aim of the research reported in this paper was to evaluate plasma concentrations of energy, oxidative and inflammatory biomarkers of Simmental (sire) × Holstein (dam) crossbred cows, in comparison with the two parental breeds during the peripartal and early lactation periods and to estimate the effects of heterosis for these traits. Thirty-three animals, managed under the same conditions, 8 Simmental (SI), 9 Holstein (HO) and 16 crossbred (CR) cows were enrolled in this study. Glucose, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), total protein, albumin, creatinine and urea were determined in blood sampled at six different time points (30 ± 3 and 15 ± 3 d before the expected calving date, at calving and 15, 30 and 60 d after calving). Furthermore, derived reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), interleukin-6 (IL-6), haptoglobin (Hp) and serum amyloid A protein (SAA) were determined to evaluate inflammatory and oxidative status. Results showed that the CR group had significantly lower average values of glucose and NEFA when compared to HO group; signifcantly lower values of urea than SI group and significantly higher values of creatinine than HO. Furthermore, CR cows showed the lowest average value of d-ROMs with respect to SI and HO parental breeds. Finally, the average value of haptoglobin was significantly lower in CR and HO groups, when compared to SI group. As for the heterosis we found the highest (positive) percentage for CK (98%) and BAP (47%) and the lowest (negative) percentage for OSi (−75%) and d-ROMs (−39%). A negative percentage was also found for the glucose (−11%) and NEFA (−20%) toward the Simmental parental breed. Our results suggest a different response among the three genetic groups during the peripartal and early lactation periods. In particular, CR and SI cows seem more adaptable regarding energy metabolism and oxidative status. Heterosis led to a positive effect on those parameters in Simmental (sire) × Holstein (dam) crossbred cows F1 population (50% Simmental and 50% Holstein).

Simple Summary Neonatal dairy calves born with an immature immune system and gut microbiota are exposed to several stressors they have to overcome early in life. Therefore, we proposed the use of gut microbiota from a pre-screened healthy adult donor adapted to the local pathogen load to perform a fecal microbiota transplantation in neonatal dairy calves. Our results suggest that early life fecal microbiota transplantation in neonatal dairy calves is a relatively safe method, influencing growth and development and possibly alleviating the stress caused by weaning procedures. Abstract This study aimed to evaluate the effects of early life fecal microbiota transplantation (FMT) on the health and performance of neonatal dairy calves. The donor was selected based on health and production records and fecal material testing negative for infectious pathogens. Sixteen healthy newborn Holstein calves were randomized to either a baseline nutritional program (CON) or 1×/d inoculations with 25 g of fecal donor material (FMT) mixed in the milk replacer (n = 8/TRT) from 8 to 12 days of age. Blood and fecal samples were collected weekly, and calves were weaned at 7 weeks of age. A TRT × Week interaction was observed in haptoglobin, which was reflected in a positive quadratic effect in FMT calves but not in CON. A trend for a TRT × Week interaction was observed in the liver function biomarker paraoxonase, which resulted in greater paraoxonase in FMT calves than CON at three weeks of age. Fecal microbial community analysis revealed a significant increase in the alpha-diversity between week 1 and week 5 for the FMT calves. These results suggest that early life FMT in neonatal calves has positive effects in mediating the inflammatory response and gut microbial maturation.

Simple Summary Fatty acids play an important role in the regulation of inflammation and oxidative stress. The birth and the neonatal period are characterized by a high risk of inflammation and an increased production of reactive oxygen species in the calf. The present study deals with the effects of a different maternal fatty acid supply including the supplementation of saturated fatty acids by coconut oil, essential fatty acids, conjugated linoleic acid or a combination of essential fatty acids and conjugated linoleic acid on the immunological and oxidative as well as anti-oxidative status of neonatal calves. Maternal essential fatty acid as well as conjugated linoleic acid supply affected the inflammatory response and the oxidative and anti-oxidative status of the neonatal offspring. Essential fatty acids might have beneficial effects on the prevention of dysregulated inflammation after birth and reduced the plasma bilirubin concentrations in this period. Conjugated linoleic acid and saturated fatty acids might increase the inflammatory response. Similarly, plasma bilirubin increased, which in part might serve as a protector against oxidative stress in the early phase after birth. Abstract Fatty acids are known for their regulatory role in inflammation and oxidative stress. The present study investigated 38 calves born from dams, abomasally supplemented with coconut oil, essential fatty acids (EFA), conjugated linoleic acid (CLA) or EFA + CLA, according to immunological traits and the oxidative and anti-oxidative status for the first 5 days of life. On day 2 of life, plasma total bilirubin, cholesterol, interleukin 1-β and ferric ion reducing anti-oxygen power (FRAP) were lower in calves with than without maternal EFA supplementation, and FRAP additionally on day 4. On day 3, the concentrations of reactive oxygen metabolites were higher in calves with than without maternal EFA supplementation and additionally on day 5 together of retinol. Total leucocyte counts were decreased in the EFA group compared to the CLA group on day 5. Lymphocyte proportions decreased from day 1 to 5 only in the EFA + CLA group. On day 2, plasma total protein was higher in CLA and EFA + CLA than in EFA calves. Similarly, CLA calves had higher interleukin 1-β concentrations compared to EFA + CLA calves. FRAP was decreased by CLA on day 4. Overall, the maternal fatty acid supply affected the inflammatory response and the oxidative and anti-oxidative status of the neonatal offspring.

Background Methionine (Met) supply during late-pregnancy enhances fetal development in utero and leads to greater rates of growth during the neonatal period. Due to its central role in coordinating nutrient and one-carbon metabolism along with immune responses of the newborn, the liver could be a key target of the programming effects induced by dietary methyl donors such as Met. To address this hypothesis, liver biopsies from 4-day old calves (n = 6/group) born to Holstein cows fed a control or the control plus ethyl-cellulose rumen-protected Met for the last 28 days prepartum were used for DNA methylation, transcriptome, metabolome, proteome, and one-carbon metabolism enzyme activities. Results Although greater withers and hip height at birth in Met calves indicated better development in utero, there were no differences in plasma systemic physiological indicators. RNA-seq along with bioinformatics and transcription factor regulator analyses revealed broad alterations in ‘Glucose metabolism’, ‘Lipid metabolism, ‘Glutathione’, and ‘Immune System’ metabolism due to enhanced maternal Met supply. Greater insulin sensitivity assessed via proteomics, and efficiency of transsulfuration pathway activity suggested beneficial effects on nutrient metabolism and metabolic-related stress. Maternal Met supply contributed to greater phosphatidylcholine synthesis in calf liver, with a role in very low density lipoprotein secretion as a mechanism to balance metabolic fates of fatty acids arising from the diet or adipose-depot lipolysis. Despite a lack of effect on hepatic amino acid (AA) transport, a reduction in metabolism of essential AA within the liver indicated an AA ‘sparing effect’ induced by maternal Met. Conclusions Despite greater global DNA methylation, maternal Met supply resulted in distinct alterations of hepatic transcriptome, proteome, and metabolome profiles after birth. Data underscored an effect on maintenance of calf hepatic Met homeostasis, glutathione, phosphatidylcholine and taurine synthesis along with greater efficiency of nutrient metabolism and immune responses. Transcription regulators such as FOXO1, PPARG, E2F1, and CREB1 appeared central in the coordination of effects induced by maternal Met. Overall, maternal Met supply induced better immunometabolic status of the newborn liver, conferring the calf a physiologic advantage during a period of metabolic stress and suboptimal immunocompetence.

Although choline requirements for cows are unknown, enhanced postruminal supply may decrease liver triacylglycerol and increase flux through the Met cycle to improve immunometabolic status during a negative nutrient balance (NNB). Our objectives were to investigate the effects of postruminal choline supply during a feed restriction-induced NNB on (1) hepatic activity cystathionine β-synthase and transcription of enzymes in the transsulfuration pathway and Met cycle; (2) hepatic metabolites in the Met cycle and the transsulfuration pathway, bile acids, and energy metabolism; and 3) plasma biomarkers of liver function, inflammation, and oxidative stress. Ten primiparous rumen-cannulated Holstein cows (158 ± 24 d postpartum) were used in a replicated 5 × 5 Latin square design with 4-d treatment periods and 10 d of recovery (14 d/period). Treatments were unrestricted intake with abomasal infusion of water, restricted intake (R; 60% of net energy for lactation requirements) with abomasal infusion of water, or R plus abomasal infusion of 6.25, 12.5, or 25 g/d choline ion. Liver tissue was collected on d 5 after infusions ended, and blood was collected on d 1, 3, and 5. Statistical contrasts were A0 versus R0 (CONT1), R versus the average of choline doses (CONT2), and tests of linear and quadratic effects of choline dose. Activity of cystathionine β-synthase was lower with R (CONT1) and decreased linearly with choline. Hepatic glutathione was not different with R or choline, but taurine tended to be greater with choline (CONT2). Betaine and carnitine were greater with R (CONT1) and further increased with choline (CONT2). Concentrations of NAD+ were greater with choline (CONT2). Cholic and glycol-chenodeoxycholic acids were decreased by R and choline, while taurocholic and tauro-chenodeoxycholic acids were not altered. Plasma aspartate aminotransferase and bilirubin were greater with R (CONT1) but decreased with choline (CONT2). Paraoxonase was lower with R and increased with choline (CONT2). Data suggest that enhanced supply of choline during NNB decreases entry of homocysteine to the transsulfuration pathway, potentially favoring remethylation to Met by acquiring a methyl group from betaine. As such, Met may provide methyl groups for synthesis of carnitine. Along with production data indicating that 12.5 g/d choline ion improved milk yield and liver fatty acid metabolism during NNB, the changes in blood biomarkers also suggest a beneficial effect of choline supply on liver function and oxidative stress.

Earlier studies indicated that the inflammatory status of dairy cows in early lactation could not be fully explained by the negative energy balance (NEB) at that moment. The objective of the present study was to determine relationships between inflammatory biomarkers and oxidative stress with uterine health in dairy cows after different dry period lengths. Holstein–Friesian dairy cows were assigned to one of three dry period lengths (0-, 30-, or 60-d) and one of two early lactation rations (glucogenic or lipogenic ration). Cows were fed either a glucogenic or lipogenic ration from 10-d before the expected calving date. Part of the cows which were planned for a 0-d dry period dried themselves off and were attributed to a new group (0 → 30-d dry period), which resulted in total in four dry period groups. Blood was collected (N = 110 cows) in weeks −3, −2, −1, 1, 2, and 4 relative to calving to determine biomarkers for inflammation, liver function, and oxidative stress. Uterine health status (UHS) was monitored by scoring vaginal discharge (VD) based on a 4-point scoring system (0, 1, 2, or 3) in weeks 2 and 3 after calving. Cows were classified as having a healthy uterine environment (HU, VD score = 0 or 1 in both weeks 2 and 3), nonrecovering uterine environment (NRU, VD score = 2 or 3 in week 3), or a recovering uterine environment (RU, VD score = 2 or 3 in week 2 and VD score= 0 or 1 in week 3). Independent of dry period length, cows with NRU had higher plasma haptoglobin (P = 0.05) and lower paraoxonase levels (P < 0.01) in the first 4 weeks after calving and lower liver functionality index (P < 0.01) compared with cows with HU. Cows with NRU had lower plasma albumin (P = 0.02) and creatinine (P = 0.02) compared with cows with a RU, but not compared with cows with HU. Independent of UHS, cows with a 0 → 30-d dry period had higher bilirubin levels compared with cows with 0-, 30-, or 60-d dry period (P < 0.01). Cows with RU and fed a lipogenic ration had higher levels of albumin in plasma compared with cows with NRU and fed a lipogenic ration (P < 0.01). In conclusion, uterine health was related to biomarkers for inflammation (haptoglobin and albumin) and paraoxonase in dairy cows in early lactation. Cows which were planned for a 0-d dry period, but dried themselves off (0 → 30-d dry period group) had higher bilirubin levels, which was possibly related to a more severe NEB in these cows. Inflammatory biomarkers in dairy cows in early lactation were related to uterine health in this period.

The increased resistance to disease observed after monensin treatment could reflect a reduction of inflammation and oxidative stress. We hypothesised that if monensin supplementation was given before calving, it would help in controlling inflammation, reduce the susceptibility to disease and increase the performance. Fourteen pregnant heifers (PR) and 24 multiparous cows (ML) were randomly assigned to a treated group (Mon) or a control group (Ctr). The Mon group received 32.4 g of monensin in a controlled-release capsule 21 days before calving (expected release rate, 335 mg/d for 95 days). Their health status, rumination activity, and plasma parameters were monitored from –28 to 56 days from calving. The milk yield (MY), milk composition, and cheese-making properties were also monitored. Rumen samples were collected at 30 days from calving to assess the volatile fatty acids composition and investigate immunological parameters. After calving, the Mon group had fewer clinical diseases, an increased rumination time, and a higher MY. Monensin reduced the infiltration of both T and B cells in rumen fluid. In ML, the Mon group had lower levels of β-hydroxybutyrate in the early postpartum period and a lower level of total reactive oxygen species. Of PR, the Mon group had a tendency for lower levels of nonesterified fatty acids, higher levels of ceruloplasmin after the first month of lactation, a tendency for lower levels of paraoxonase, higher levels of γ-glutamyl transferase and higher levels of total reactive oxygen species. Monensin treatment decreased the cheese-making properties in the milk of PR.HighlightsMonensin improved the performance of all the animals and decreased the disease incidence in all of them.Monensin heightened the inflammatory and oxidative stress status and reduced the cheese-making properties in pregnant heifers.Although different effects were seen in cows with different parity, dairy cows generally beneficed of monensin administration. Monensin improved the performance of all the animals and decreased the disease incidence in all of them. Monensin heightened the inflammatory and oxidative stress status and reduced the cheese-making properties in pregnant heifers. Although different effects were seen in cows with different parity, dairy cows generally beneficed of monensin administration.

Background Pregnancy and early life are critical periods of plasticity during which the fetus and neonate may be influenced by environmental factors such as nutrition. Maternal methionine (Met) supply in non-ruminants during pregnancy can affect offspring development and growth. Thus, the objective of this study was to investigate if increasing Met supply during late-pregnancy affects developmental parameters of the calf at birth and if either maternal Met or colostrum from Met-fed cows alters calf growth. Calves born to Holstein cows individually-fed a basal control [CON; 1.47 Mcal/kg dry matter (DM) and 15.3% crude protein] diet with no added Met or CON plus ethylcellulose rumen-protected Met (MET; Mepron® at 0.09% of diet DM; Evonik Nutrition & Care GmbH, Germany) during the last 28 ± 2 d of pregnancy were used. A total of 39 calves were in CON (n = 22 bulls, 17 heifers) and 42 in MET (n = 20 bulls, 22 heifers). At birth, calves were randomly allocated considering dam treatment and colostrum as follows: 1) calves from CON cows and colostrum from CON cows (n = 21); 2) calves from CON cows and colostrum from MET cows (n = 18); 3) calves from MET cows and colostrum from MET cows (n = 22); and 4) calves from MET cows and colostrum from CON cows (n = 20). All calves were housed, managed, and fed individually during the first 9 wk of life. Results Despite greater daily DM intake pre-partum in cows fed MET (15.7 vs. 14.4 ± 0.12 kg/d, P 0.05) due to maternal Met supply or colostrum source. However, fecal scores tended to be lower (P ≤ 0.10) in MET calves regardless of colostrum source. Conclusions Increasing the maternal supply of MET during late-pregnancy enhanced growth in utero as well as during the pre-weaning and early post-weaning periods. Although the ~ 1 kg/d greater DM intake during the last 2–3 wk prior to parturition could explain a portion of the 2 kg extra body mass of MET calves at birth, other mechanisms potentially encompassing nutrient assimilation efficiency likely played a role. Assessing the exact mechanisms sensitive to supply of Met or total amino acid supply during the latter stages of growth in utero merit further research. Electronic supplementary material The online version of this article (10.1186/s40104-018-0298-1) contains supplementary material, which is available to authorized users.

Measurements of energy balance (EB) require the use of respiration chambers, which are quite expensive and laborious. The GreenFeed (GF) system (C-Lock Inc.) has been developed to offer a less expensive, user friendly alternative. In this study, we used the GF system to estimate the EB of cows in early lactation and compared it with EB predicted from energy requirements for dairy cows in the Finnish feeding standards. We also evaluated the association between milk fatty acids and the GF estimated EB. The cows were fed the same grass silage but supplemented with either cereal grain or fibrous by-product concentrate. Cows were followed from 1 to 18 wk of lactation, and measurements of energy metabolism variables were taken. Data were subjected to ANOVA using the mixed model procedure of SAS (SAS Institute Inc.). The repeatability estimates of the gaseous exchanges from the GF were moderate to high, presenting an opportunity to use it for indirect calorimetry in EB estimates. Energy metabolism variables were not different between cows fed different concentrates. However, cows fed the grain concentrate produced more methane (24.0 MJ/d or 62.9 kJ/MJ of gross energy) from increased digestibility than cows fed the by-product concentrate (21.3 MJ/d or 56.5 kJ/MJ of gross energy). Nitrogen metabolism was also not different between the diets. Milk long-chain fatty acids displayed an inverse time course with EB and de novo fatty acids. There was good concordance (0.85) between EB predicted using energy requirements derived from the Finnish feed table and EB estimated by the GF system. In conclusion, the GF can accurately estimate EB in early-lactating dairy cows. However, more data are needed to further validate the system for a wide range of dietary conditions.

Metabolic disorders, including hepatic lipidosis and ketosis, severely affect animal health status and welfare with a large economic burden in dairy herds. The gold standard for diagnosing hepatic lipidosis is the liver biopsy, which is impractical and invasive for the screening at farm level. Ultrasound (US) imaging is a promising technique for identifying liver dysfunction, but standardized specifications in physiological conditions are needed. Herein, we described the features of four US measurements, namely the liver predicted triacylglycerol (pTAG) content, liver depth (LD), and portal vein area (PVA) and depth (PVD) and we investigated their associations with a set of hematochemical (HC) indicators in 342 clinically healthy Holstein Friesian dairy cows. Liver pTAG content was negatively associated with hematocrit and positively with globulin, whereas PVA was negatively associated with thiol group levels, and LD positively with ceruloplasmin. We found significant interactions between some HC parameters and parity: in particular, creatinine, thiol groups and globulin for PVA, and aspartate aminotransferase, paraoxonase and ceruloplasmin for PVD. This study offers new insights on variations in liver function occurring after calving and pave the way for the potential use of minimally invasive techniques for prompt detection of metabolic disorders in dairy herds.

We investigated how prepartal body condition score (BCS) alters key hepatic enzymes associated with 1-carbon, carnitine, and glutathione metabolism and the related biomarkers in liver tissue and plasma of periparturient dairy cows. Twenty-six multiparous Holstein dairy cows were retrospectively selected according to BCS at 4 wk prepartum and divided into high (HighBCS, BCS ≥ 3.50) and normal (NormBCS, BCS ≤ 3.25) BCS groups (n = 13 each). Blood plasma samples were obtained at -30, -10, 7, 15, and 30 d relative to calving. Liver tissue biopsies were performed at -15, 7, and 30 d relative to calving, and samples were used to assess protein abundance via Western blot assay. Cows in the HighBCS group lost ∼1 unit of BCS between -4 and 4 wk around calving, while NormBCS cows lost ∼0.5 unit in the same period. Prepartal dry matter intake (DMI, kg/d) did not differ between groups. Compared with NormBCS cows, HighBCS cows had higher postpartal DMI and milk yield (+5.34 kg/d). In addition, greater overall plasma concentrations of fatty acids and activity of the neutrophil-enriched enzyme myeloperoxidase were observed in HighBCS compared with NormBCS cows. Despite similar reactive oxygen metabolite concentrations in both groups at 30 d, HighBCS cows had lower overall concentrations of β-carotene and tocopherol, explaining the lower (BCS × Time) antioxidant capacity (ferric reducing ability of plasma). The HighBCS cows also had greater liver malondialdehyde concentrations and superoxide dismutase activity at 30 d. Overall, compared with NormBCS cows, HighBCS cows had lower hepatic protein abundance of the 1-carbon metabolism enzymes cystathionine-β-synthase, betaine-homocysteine methyltransferase, and methionine adenosyltransferase 1 A (MAT1A), as well as the glutathione metabolism-related enzymes glutathione S-transferase α 4 and glutathione peroxidase 3 (GPX3). A lower protein abundance of glutathione S-transferase mu 1 (GSTM1) at -15 and 7 d was also observed. Regardless of BCS, cows had increased abundance of GSTM1 and GPX3 between -15 and 7 d around calving. A marked decrease of gamma-butyrobetaine dioxygenase 1 from -10 to 7 d in HighBCS compared with NormBCS cows suggested a decrease in de novo carnitine synthesis that was partly explained by the lower abundance of MAT1A. Overall, data suggest biologic links between BCS before calving, milk yield, immune response, and hepatic reactions encompassing 1-carbon metabolism, carnitine, and antioxidant synthesis.

Background Nutritional management in the dry period can alter body condition score (BCS) in dairy cows, a subjective measure of body fat. As such, differences in BCS during late-pregnancy not only mirror nutrient utilization by fat depots, but also can play important roles on the metabolic and hormonal environment. We investigated the association between cow BCS during late-pregnancy on developmental parameters and blood variables of neonatal calves. Forty-nine multiparous Holstein cows were retrospectively divided by prepartal BCS into normal BCS ≤3.25 (NormBCS; 3.02 ± 0.17, n = 30) or high BCS ≥3.75 (HighBCS; 3.83 ± 0.15, n = 19) groups. Plasma samples were collected from cows at − 10 d relative to parturition. Body weight, hip and wither height, hip width and body length were measured at birth and weekly through weaning (42 d of age) and until 9 weeks of age. Calf blood samples were collected from the jugular vein at birth (before receiving colostrum, 0 d), 24 h after first colostrum and at 7, 21, 42 and 50 d of age. The data were subjected to ANOVA using the mixed procedure of SAS. The statistical model included day, BCS, and their interactions. Results Dry matter intake (kg/d or % of body weight) during the last 4 weeks of pregnancy was lower (P ≤ 0.06) in HighBCS cows. Plasma concentrations of fatty acids, ceruloplasmin, and nitric oxide were greater overall (P P = 0.08) to have greater concentrations of reactive oxygen metabolites. Birth body weight was lower (P = 0.03) in calves born to dams with HighBCS. In addition, plasma concentrations of fatty acids, albumin and urea (P P = 0.04), hip and wither height, hip width, and body length, there was no difference (P > 0.05) in daily starter intake and average daily gain due to maternal BCS. Conclusions Overall, results highlight an association between BCS during late-gestation on in utero calf development and postnatal growth. A high maternal BCS during late-gestation was associated with lower calf body weights, which could be due to lower maternal intakes and a state of inflammation and metabolic stress.

An unsupervised machine learning approach (ML) of rumination time (RT) data was used to evaluate metabolic and lactation performance in a cohort of Simmental dairy cows (29) around parturition. The k-means clustering (unsupervised ML) was used to generate clusters based on RT (Hr-Tags; SCR by Allflex) over 24 h from 1 to 7-d post-calving. Two large clusters were obtained: high (High-RT, n = 13) and low (Low-RT, n = 12). Milk production was recorded until 42 d in lactation and milk samples collected weekly. Blood samples were collected from −21 to +28 d relative to calving. Data were subjected to PROC MIXED of SAS. Compared with Low-RT, High-RT cows had lower plasma BHB (3, 7, and 14 d), haptoglobin (3 and 7 d), and non-esterified fatty acids (1 and 3 d). High-RT cows had greater tocopherol from 3 to 28 d, fructosamine and albumin at 7 d, and retinol at 3 and 7 d after calving than Low-RT cows. Compared with multiparous Low-RT, milk production was greater in multiparous High-RT cows, but no differences were detected for primiparous. Only for multiparous, High-RT cows displayed a greater LFI than Low-Rt cows. The close relationship between RT and the physiological state at the onset of lactation supports the use of RT as an indicator of metabolic and inflammatory adaptations to the negative energy balance of cows after parturition. At the farm level, these outcomes provide information to farmers that can be helpful in management decisions for cow health, complementing traditional methods.HIGHLIGHTSThe unsupervised ML applied was able to group cows with different RT increase rates after calving based on differences in plasma biomarkers of energy metabolism, inflammatory response, and liver functionality, particularly in multiparous cows.A quicker increase in RT after calving was associated with a lower inflammatory response, lower lipid mobilisation, and greater milk production.At the farm level, the fine-tuning of specific algorithm in the actual sensors considering the rate of increase of RT after calving can be helpful in management decisions for cow health, complementing traditional methods to better monitor early lactation dairy cows. The unsupervised ML applied was able to group cows with different RT increase rates after calving based on differences in plasma biomarkers of energy metabolism, inflammatory response, and liver functionality, particularly in multiparous cows. A quicker increase in RT after calving was associated with a lower inflammatory response, lower lipid mobilisation, and greater milk production. At the farm level, the fine-tuning of specific algorithm in the actual sensors considering the rate of increase of RT after calving can be helpful in management decisions for cow health, complementing traditional methods to better monitor early lactation dairy cows.

Background We aimed to characterize the protective effects and the molecular mechanisms of action of a Saccharomyces cerevisiae fermentation product (NTK) in response to a mastitis challenge. Eighteen mid-lactation multiparous Holstein cows (n = 9/group) were fed the control diet (CON) or CON supplemented with 19 g/d NTK for 45 d (phase 1, P1) and then infected in the right rear quarter with 2500 CFU of Streptococcus uberis (phase 2, P2). After 36-h, mammary gland and liver biopsies were collected and antibiotic treatment started until the end of P2 (9 d post challenge). Cows were then followed until day 75 (phase 3, P3). Milk yield (MY) and dry matter intake (DMI) were recorded daily. Milk samples for somatic cell score were collected, and rectal and udder temperature, heart and respiration rate were recorded during the challenge period (P2) together with blood samples for metabolite and immune function analyses. Data were analyzed by phase using the PROC MIXED procedure in SAS. Biopsies were used for transcriptomic analysis via RNA-sequencing, followed by pathway analysis. Results DMI and MY were not affected by diet in P1, but an interaction with time was recorded in P2 indicating a better recovery from the challenge in NTK compared with CON. NTK reduced rectal temperature, somatic cell score, and temperature of the infected quarter during the challenge. Transcriptome data supported these findings, as NTK supplementation upregulated mammary genes related to immune cell antibacterial function (e.g., CATHL4, NOS2), epithelial tissue protection (e.g. IL17C), and anti-inflammatory activity (e.g., ATF3, BAG3, IER3, G-CSF, GRO1, ZFAND2A). Pathway analysis indicated upregulation of tumor necrosis factor α, heat shock protein response, and p21 related pathways in the response to mastitis in NTK cows. Other pathways for detoxification and cytoprotection functions along with the tight junction pathway were also upregulated in NTK-fed cows. Conclusions Overall, results highlighted molecular networks involved in the protective effect of NTK prophylactic supplementation on udder health during a subclinical mastitic event.

The dry-off of dairy cows represents an important phase of the lactation cycle, influencing the outcome of the next lactation. Among the physiological changes, the severity of the inflammatory response can vary after the dry-off, and this response might have consequences on cow adaptation in the transition period. The plasma protein profile is a diagnostic tool widely used in humans and animals to assess the inflammatory status and predict the outcome of severe diseases. The albumin-to-globulin ratio (AG) can represent a simple and useful proxy for the inflammatory condition. In this study, we investigated the relationship between AG before dry-off and inflammation, metabolic profile, and performance of 75 Holstein dairy cows. Blood samples were collected from -62 (7 d before dry-off) to 28 d relative to calving (DFC) to measure metabolic profile biomarkers, inflammatory variables, and liver function. Daily milk yield in the first month of lactation was recorded. Milk composition, body condition score, fertility, and health status were also assessed. The AG calculated 1 wk before dry-off (-62 DFC) was used to retrospectively group cows into tertiles (1.06 ± 0.09 for HI, 0.88 ± 0.04 for IN, and 0.72 ± 0.08 for LO). Data were subjected to ANOVA using the PROC MIXED program in SAS software. Differences among groups observed at -62 DFC were almost maintained throughout the period of interest, but AG peaked before calving. According to the level of acute-phase proteins (haptoglobin, ceruloplasmin, albumin, cholesterol, retinol-binding protein), bilirubin, and paraoxonase, a generally overall lower inflammatory condition was found in HI and IN than in the LO group immediately after the dry-off but also after calving. The HI cows had greater milk yield than LO cows, but no differences were observed in milk composition. The somatic cell count reflected the AG ratio trend, with higher values in LO than IN and HI either before dry-off or after calving. Fertility was better in HI cows, with fewer days open and services per pregnancy than IN and LO cows. Overall, cows with high AG before dry-off showed an improved adaptation to the new lactation, as demonstrated by a reduced systemic inflammatory response and increased milk yield than cows with low AG. In conclusion, the AG ratio before dry-off might represent a rapid and useful proxy to evaluate the innate immune status and likely the ability to adapt while switching from the late lactation to the nonlactating phase and during the transition period with emphasis on early lactation.

Mastitis is one of the most prevalent diseases in dairy cattle and is the cause of considerable economic losses. Alongside somatic cell count (SCC), differential somatic cell count (DSCC) has been recently introduced as a new indicator of intramammary infection. The DSCC is expressed as a count or a proportion (%) of polymorphonuclear neutrophils plus lymphocytes (PMN-LYM) in milk somatic cells. These numbers are complemented to total somatic cell count or to 100 by macrophages (MAC). The aim of this study was to investigate the genetic variation and heritability of DSCC, and its correlation with milk composition, udder health indicators, milk composition, and technological traits in Holstein cattle. Data used in the analysis consisted in single test-day records from 2,488 Holstein cows reared in 36 herds located in northern Italy. Fourier-transform infrared (FTIR) spectroscopy was used to predict missing information for some milk coagulation and cheese-making traits, to increase sample size and improve estimation of the genetic parameters. Bayesian animal models were implemented via Gibbs sampling. Marginal posterior means of the heritability estimates were 0.13 for somatic cell score (SCS); 0.11 for DSCC, MAC proportion, and MAC count; and 0.10 for PMN-LYM count. Posterior means of additive genetic correlations between SCS and milk composition and udder health were low to moderate and unfavorable. All the relevant genetic correlations between the SCC traits considered and the milk traits (composition, coagulation, cheese yield and nutrients recovery) were unfavorable. The SCS showed genetic correlations of -0.30 with the milk protein proportion, -0.56 with the lactose proportion and -0.52 with the casein index. In the case of milk technological traits, SCS showed genetic correlations of 0.38 with curd firming rate (k20), 0.45 with rennet coagulation time estimated using the curd firming over time equation (RCTeq), -0.39 with asymptotic potential curd firmness, -0.26 with maximum curd firmness (CFmax), and of -0.31 with protein recovery in the curd. Differential somatic cell count expressed as proportion was correlated with SCS (0.60) but had only 2 moderate genetic correlations with milk traits: with lactose (-0.32) and CFmax (-0.33). The SCS was highly correlated with the log PMN-LYM count (0.79) and with the log MAC count (0.69). The 2 latter traits were correlated with several milk traits: fat (-0.38 and -0.43 with PMN-LYM and MAC counts, respectively), lactose percentage (-0.40 and -0.46), RCTeq (0.53 and 0.41), tmax (0.38 and 0.48). Log MAC count was correlated with k20 (+0.34), and log PMN-LYM count was correlated with CFmax (-0.26) and weight of water curd as percentage of weight of milk processed (-0.26). The results obtained offer new insights into the relationships between the indicators of udder health and the milk technological traits in Holstein cows.

Background: the peripartum is the most critical period in dairy cows with high incidence of diseases due to immune dysfunctions, often paired with systemic inflammation and oxidative stress. Selenium is a trace mineral that plays an important role in anti-oxidative function and immune response. We hypothesize that supplementing dairy cows with a relatively small amount of Se-biofortified hay during the last 40 days of pregnancy and early lactation improves performance, metabolism, oxidative status, and immune response.Methods: ten Jersey and 8 Holstein pregnant dairy heifers were divided into two groups and supplemented with 1 kg/100 kg BW of Se-biofortified (Sel; n=9; 3.2 ppm Se) or non-biofortified (Ctr; n=9; 0.4 ppm Se) alfalfa hay from 40 days prior- to 2 weeks post-partum. Heifers were monitored daily for feed intake, activity, and milk yield, and weekly for BW and BCS. Milk samples were assessed for components and fatty acid profile. Blood samples were collected regularly to assess metabolic, oxidative, and inflammatory biomarkers, and to evaluate leukocytes phagocytosis and differential through flow cytometry.Results: supplementation of Se biofortified hay did not affect feed intake, milk yield, BW, BCS, milk components, and any of the parameters measured on leukocytes but increased the hematocrit. Animal receiving Se biofortified hay had larger concentration of plasma albumin and a tendency for larger blood urea, indicating a possible better liver status, especially post-partum. None of the parameters measured in plasma related to the oxidative status were affected, except the concentration of advanced oxidation protein products that was greater in Sel vs. Ctr. The concentration of advanced oxidation protein products was negatively correlated with parameters related to inflammation but positively associated to plasma albumin suggesting a possible improved anti-oxidative function of circulating albumin by Se-biofortified hay supplementation.Conclusions: feeding Se-biofortified hay during pregnancy in dairy heifers had little effect on metabolic, inflammatory, and oxidative status parameters with no effect on performance or immune response. Supplementation with Se-biofortified hay increased plasma level of albumin, possibly as consequence of improved liver function, promoting the antioxidant role of albumin as indicated by increased AOPP.

Pegbovigrastim is a commercial long-acting analog of bovine granulocyte colony-stimulating factor (rbG-CSF) that promotes the increased count and functionality of polymorphonuclear cells in dairy cows around the time of parturition. We hypothesized that pegbovigrastim administered to periparturient cows at approximately seven days before parturition and within 24 hours after calving could affect the profiles of gene networks involved in leukocyte function. Blood was collected on Day 3 after calving from treated groups (pegbovigrastim (PEG), 13 Simmental (seven multiparous and six primiparous) and 13 Holstein (seven multiparous and six primiparous) cows) that received pegbovigrastim (Imrestor, Elanco Animal Health) and controls (CTR, 13 Simmental (seven multiparous and six primiparous) and 13 Holstein (six multiparous and seven primiparous) cows) that received saline solution. Blood from all cows was sampled from the jugular vein in a PAXgene Blood RNA System tube (Preanalytix, Hombrechtikon, Switzerland) for RNA extraction. The RT-qPCR analysis was performed to investigate a panel of 34 genes of interest, representing recognition, immune mediation, migration, cell adhesion, antimicrobial strategies, inflammatory cascade, oxidative pattern, and leukotrienes in whole blood leukocytes. Normalized data were subjected to the MIXED model of SAS (ver. 9.4) with treatment, breed, parity, and their interaction as fixed effects. Compared with CTR, whole blood leukocytes of PEG cows had higher expression of genes involved in recognition and immune modulation (CD14, CD16, MYD88, TLR2, and TLR4), cell adhesion (ITGB2, ITGAL, TLN1, SELL, SELPLG, and CD44), antimicrobial activity (MMP9, LTF, and LCN2), and inflammatory cascade (CASP1, TNFRSF1A, IL1B, IL1R, IL18, IRAK1, NLRP3, and S100A8). This suggested an improvement of migration, adhesion, and antimicrobial ability and an enhanced inflammatory response, which in turn could trigger immune cell activation and enhance function. Expression of SOD2 and ALOX5 was also greater in the PEG group. In contrast, compared with CTR cows, PEG led to lower expression of RPL13A, ALOX15, IL8, and TNF. Overall, leukocytes from Simmental compared with Holstein cows had greater expression of IDO1, RPL13A, ALOX5, CD44, CX3CR1, ITGB2, and TNFA, whereas expression of CD16 and TLR2 was lower. Overall, compared with multiparous cows, primiparous cows had higher expression of IL1B, IL18, MYD88, SELL, and TLR2 and lower expression of MMP9. Simmental cows seemed more sensitive to induction of the immune system after calving, as revealed by the greater abundance of genes involved in immune system adaptation, regardless of pegbovigrastim treatment. Primiparous cows undergoing a new stress condition with respect to older cows were characterized by leukocytes with a higher inflammatory response. In conclusion, pegbovigrastim led to higher expression levels of most genes involved in the processes investigated, suggesting a thorough activation of the immune machinery during the critical post-partum period.

The objective of this study was to assess how uterine disorders alter the lying behaviour and plasma biomarkers in dairy cows. 34 multiparous cows were retrospectively classified into three groups according to the first uterine disorder that cows were diagnosed with: retained placenta (RP), metritis (MET), or healthy (H; cows without any clinical disease). Lying time (LT) and duration of lying bouts (LB) were monitored between 6 weeks prior to and 8 weeks after calving via the AfiAct II pedometer. Blood samples were collected routinely between 14 days before and 28 days after calving. Data was analysed using Proc MIXED of SAS ver. 9.4. Regardless of grouping, both LT and LB were longer (P 0.01) in the prepartum period (774 ± 16.6 min/day and 89.9 ± 2.1 min/bout) than in the first 28 days after calving (DFC; 653 ± 16.7 min/day and 63.7 ± 2.1 min/bout). Cows with RP had longer LT than healthy cows during the last 3 weeks before calving (837 ± 30.9 vs. 735 ± 27.1 min/day; P 0.05). LT in cows with MET and healthy cows were not significantly different. The LB was similar among groups, averaging 76.1 ± 3.4 min/bout in healthy cows, 73.2 ± 3.8 min/bout in cows with RP, and 75.2 ± 3.7 min/bout in cows with MET (P 0.05). Compared with healthy cows, cows with RP laid down longer and stood up for shorter times (P 0.05), particularly before calving. In addition, cows with RP had increased mobilization of body stores and more pronounced inflammatory status, as demonstrated by plasma haptoglobin (P = 0.04) and albumin (P 0.01) concentrations. Our data suggest that automatic monitoring of lying behaviour could help identify cows at increased risk of developing certain disorders, such as RP.

The present experiment aimed to investigate (1) the effect of weaning age on rumen fermentation, dietary intake, growth, and rumination behavior at 20 d after weaning in Simmental calves, and (2) the relationship between rumination time measured by the Hr-Tag rumination-monitoring system (Hr-Tag; SCR Engineers Ltd, Netanya, Israel) and rumen fermentation variables. Ten Simmental calves were randomly assigned at birth to be weaned at 45 (early weaning, EW) or 60 d of age (normal weaning, NW). EW calves were offered 6 L of bulk whole milk/d from d 2 to 38 and 3 L/d from d 39 to 45, while NW were offered 6 L of bulk whole milk/d from d 2 to 53 and 3 L/d from d 54 to 60. Individual calf starter intake was recorded daily and average daily gain (ADG) was calculated taken into account the BW at 6 d after weaning and final BW at 20 d after weaning. On d 20 after weaning, samples of rumen fluid were obtained via an esophageal tube. These samples were used to determine pH and volatile fatty acids (VFAs) concentration. Throughout the entire experiment, the Hr-Tag system continuously recorded the rumination time (RT) by Hr-Tag loggers positioned on the left side of the neck. No treatment differences were detected for total VFAs concentration and molar proportion of acetate, propionate, and butyrate (P > 0.05). Overall in the period -25 to 20 d relative to weaning time, daily RT did not differ between NW and EW calves and it increased around weaning in both groups. Hr-Tags revealed no differences in daily RT pattern (2h-RT) during the 3 d before rumen collection, while during the day (24 h) 2h-RT significantly varied overall in both EW and NW groups. Daily RT measured by Hr-Tags positively correlated to pH (r = 0.98; P

[EN] Peripartal cows mobilize not only body fat but also body protein to satisfy their energy requirements. The objective of this study was to determine the effect of prepartum BCS on blood biomarkers related to energy and nitrogen metabolism, and mRNA and protein abundance associated with AA metabolism and insulin signaling in subcutaneous adipose tissue (SAT) in peripartal cows. Twenty-two multiparous Holstein cows were retrospectively classified into a high BCS (HBCS; n = 11, BCS >= 3.5) or normal BCS (NBCS; n = 11, BCS, Y. Liang is a recipient of a doctoral fellowship from the China Scholarship Council (CSC, Beijing, China) to perform his PhD studies at the University of Illinois (Urbana). A. S. Alharthi received a fellowship from King Saud University (Riyadh, Saudi Arabia) to perform his PhD studies at the University of Illinois (Urbana). A. A. Elolimy was recipient of a fellowship from the Higher Education Ministry (Cairo, Egypt) to perform his PhD studies at the University of Illinois (Urbana). We thank Perdue AgriBusiness (Salisbury, MD) for the donation of ProvAAL2 AADvantage during the course of the experiment. The authors declare no conflicts of interest.

The aim of this study was to investigate changes in the abundance of genes involved in leukocyte function between cows highly specialized for milk production (Holstein, n = 12) and cows selected for meat and milk (Simmental, n = 13). Blood was collected on d 3 after calving in PAXgene tubes (Preanalytix, Hombrechtikon, Switzerland) to measure mRNA abundance of 33 genes. Normalized gene abundance data were subjected to MIXED model ANOVA using SAS (SAS Institute Inc. Cary, NC). Simmental cows had greater transcript abundance of proinflammatory cytokines and receptor genes (IL1B, TNF, IL1R, TNFRSF1A), cell migration- and adhesion-related genes (CX3CR1, ITGB2, CD44, LGALS8), and the antimicrobial IDO1 gene. In contrast, compared with Holstein cows, Simmental cows had lower abundance of the toll-like receptor (TLR) recognition-related gene TLR2, the antimicrobial-related gene LTF, and S100A8, which is involved in cell maturation, regulation of inflammatory processes, and immune response. These results revealed that breed plays an important role in the modulation of genes involved in immune adaptation and inflammatory response, and the immune system of Simmental cows could potentially have a more acute response in early lactation. In turn, this might be beneficial for mounting a more efficient response after calving and allow for a smoother homeorhetic adaptation to lactation.

Dairy cows are exposed to increased inflammatory processes in the transition period from late pregnancy to early lactation. Essential fatty acids (EFA) and conjugated linoleic acid (CLA) are thought to modulate the inflammatory response in dairy cows. The present study investigated the effects of a combined EFA and CLA infusion on the fatty acid (FA) status in plasma lipids, and whether changes in the FA pattern were associated with the acute phase and inflammatory response during late pregnancy and early lactation. Rumen-cannulated Holstein cows (n = 40) were assigned from wk 9 antepartum to wk 9 postpartum to 1 of 4 treatment groups. Cows were abomasally supplemented with coconut oil (CTRL, 76 g/d), linseed and safflower oil (EFA, 78 g/d of linseed oil and 4 g/d of safflower oil; ratio of oils = 19.5:1; n-6:n-3 FA ratio = 1:3), Lutalin (CLA, 38 g/d; isomers cis-9,trans-11 and trans-10,cis-12; each 10 g/d), or both (EFA+CLA). Blood samples were taken to measure changes in FA in blood plasma on d -63, -42, 1, 28, and 56, and in plasma lipid fractions (cholesterol esters, free fatty acids, phospholipids, and triglycerides) on d -42, 1, and 56 relative to calving, and in erythrocyte membrane (EM) on d 56 after calving. Traits related to the acute phase response and inflammation were measured in blood throughout the study. Liver samples were obtained for biopsy on d -63, -21, 1, 28, and 63 relative to calving to measure the mRNA abundance of genes related to the inflammatory response. The concentrations of α-linolenic acid and n-3 FA metabolites increased in lipid fractions (especially phospholipids) and EM due to EFA supplementation with higher α-linolenic acid but lower n-3 metabolite concentrations in EFA+CLA than in EFA treatment only. Concentration of linoleic acid decreased in plasma fat toward calving and increased during early lactation in all groups. Concentration of plasma arachidonic acid was lower in EFA- than in non-EFA-treated groups in lipid fractions and EM. The cis-9,trans-11 CLA increased in all lipid fractions and EM after both CLA treatments. Plasma haptoglobin was lowered by EFA treatment before calving. Plasma bilirubin was lower in EFA and CLA than in CTRL at calving. Plasma concentration of IL-1β was higher in EFA than in CTRL and EFA+CLA at certain time points before and after calving. Plasma fibrinogen dropped faster in CLA than in EFA and EFA+CLA on d 14 postpartum. Plasma paraoxonase tended to be elevated by EFA treatment, and was higher in EFA+CLA than in CTRL on d 49. Hepatic mRNA abundance revealed time changes but no treatment effects with respect to the inflammatory response. Our data confirmed the enrichment of n-3 FA in EM by EFA treatment and the inhibition of n-3 FA desaturation by CLA treatment. The elevated n-3 FA status and reduced n-6:n-3 ratio by EFA treatment indicated a more distinct effect on the inflammatory response during the transition period than the single CLA treatment, and the combined EFA+CLA treatment caused minor additional changes on the anti-inflammatory response.

The anti-hyperlipidemic and anti-inflammatory effects exerted by Aloe on monogastric mammals suggest it as a potential strategy to address the tremendous metabolic alterations that affect dairy cows during their transition to calving. A group of 20 multiparous Italian Holstein dairy cows were housed in freestalls and allocated into two homogeneous groups to receive either 200 g/d of water (CTR) or 200 g/day of Aloe arborescens Mill. whole plant homogenate through a rumen tube (AAM) between &minus, 14 and 14 days from calving (DFC). From &minus, 14 to 35 DFC, the BCS, and milk yield were measured, and blood samples were collected to assess the hematochemical profile. Data underwent ANOVA testing using a mixed model for repeated measurements, including the treatment and time and their interactions as fixed effects. Compared to CTR cows, AAM cows had a less pronounced BCS loss in early lactation (p &lt, 0.01), indicating less mobilization of body reserves. Compared to CTR cows, AAM cows had a lower plasma concentration of nonesterified fatty acids and beta hydroxybutyrate (p &lt, 0.01 and = 0.01 respectively) that, paired with the lower butterfat content and fat/protein ratio in their milk (p = 0.03 and &lt, 0.01 respectively), indicates that Aloe reduced the mobilization of body fats. AAM cows had a reduced concentration of myeloperoxidase in plasma and a lower SCC in milk compared to CTR cows (p = 0.02 for both), indicating an anti-inflammatory effect of Aloe. Furthermore, AAM cows had a lower plasma concentration of ceruloplasmin (p &lt, 0.05) and higher plasma concentration of cholesterol, retinol, and paraoxonase compared to CTR cows (p &lt, 0.01, &lt, 0.01 and &lt, 0.05 respectively), indicating Aloe was effective in mitigating the acute phase response in early lactation. Finally, AAM cows had lower plasma creatinine concentrations around calving (p &lt, 0.05), a lower concentration of plasma bilirubin, and a higher concentration of plasma tocopherol compared to CTR cows (p = 0.01 for both). These data suggest Aloe has anti-hyperlipidemic and anti-inflammatory effects on transition dairy cows that could have ameliorated liver and kidney function disruption and increased the availability of body antioxidants in early lactation.

10 páginas, 5 tablas, 2 figuras., Undernutrition during the first stages of life may impair maturation of the immune system, harming the health status permanently. Thus, the aim of the present study was to define the impact of moderated milk replacer (MR) restriction during the artificial rearing period on the gut-associated lymphoid tissues of pre-weaned ewe lambs and long-term effects on biochemical profile and animal performance during the replacement period. Forty female Assaf lambs [average live body weight (LBW) 4.73 +/- 0.116 kg] were penned individually. The first group of lambs (n = 20) was fed MR ad libitum (ADL) whereas the second one (restricted, RES; n = 20) only received approximately 62.5% of the MR intake measured in the ADL group. All the lambs were weighed twice a week until they were 35-days-old. Then, 8 lambs from each group (preweaned) were harvested and ileal samples collected. The rest of the lambs (12 ADL vs. 12 RES) were weaned progressively, and then offered a total mixed ration (TMR) ad libitum until the end of the experiment (7.5-months-old). The lower nutrient intake of RES pre-weaned lambs caused greater percentages for T lymphocytes (CD4+, CD8(+), WC1(+)) and an increased secretory immunoglobulin A (sIgA) production in the ileum compared to the ADL group (P < 0.05). These results, together with the significant differences in the expression of toll-like receptors and cytokines at this level (e.g., interferon gamma was increased in the RES group; P < 0.05) suggest the existence of pro-inflammatory conditions in the ileum of pre-weaned lambs promoted by early feed restriction. Moreover, the biochemical profile revealed that liver function (e.g., albumin, gamma glutamyl transpeptidase) was impaired during several months once the feed restriction period was finished, whereas the average daily gain during the replacement phase was reduced for the early feed restricted lambs (182 vs. 202 g/day for RES and ADL groups, respectively; P < 0.05). Therefore it can be concluded that moderated MR restriction promoted both, pro-inflammatory conditions at heal level in the pre-weaned lambs and an altered liver function which lasted several months after the end of feed restriction. Both circumstances might have impaired animal performance during the replacement phase of the ewe lambs., Spanish Ministry of Economy, Industry and Competitiveness (MINECO) AGL2014-54124R; CSIC (Proyecto Intramural Especial; 201540E084); Ayudas Puente Formativas (Universidad de Leon); Spanish Ministry of Education, Culture and Sport (MECD, FPU15/01630).

A degree of negative energy balance is commonly experienced by cows during early lactation. This physiological state, if pronounced or prolonged, leads to partial oxidation of nonesterified fatty acids as an energy source and, consequently, increasing blood β-hydroxybutyrate (BHB) concentrations and potentially development of ketosis in postpartal dairy cows. Twenty-four multiparous Holstein cows received a common prepartal and postpartal diet. Cows were fitted with an accelerometer mounted laterally on the distal left hind leg using vet wrap from -30 to 15 d relative to parturition. A retrospective analysis was performed using the postpartal BHB data at 8 time points from 0 to 15 d in milk measured with the Precision Xtra (Abbott Diabetes Care, Alameda, CA). Cows with an average blood BHB

The present experiment aimed to evaluate the potential of the Hr-Tag rumination-monitoring system (Hr-Tag; SCR Engineers Ltd., Netanya, Israel) to describe the variation in rumination activity behavior in pre-weaned calves from 2 until 35 days of age. The study was carried out in a commercial farm and involved 9 Italian Simmental calves (3 females and 6 males). All calves were provided ad libitum access to water and starter throughout the study and were offered 6 L of bulk whole milk/d from an open-bucket starting at day 2 from birth and through 5 weeks. The Hr-Tag system continuously recorded the rumination time (RT) by Hr-Tag loggers positioned on the left side of the neck, and data were summarized in 2-h intervals. RT recorded by Hr-Tag loggers increased (P

Many production diseases of dairy cows are related to digestive troubles. The rumen subacute acidosis is the most relevant one, albeit not easily recognized. Recent studies suggest that forestomachs can perform regulatory actions at both regional and systemic levels, since forestomach walls express immune receptors and cytokines, and the rumen liquor is infiltrated by leukocytes. Therefore, the rumen fluid could be conveniently collected for investigating metabolic production diseases. Thus, we investigated the origin of the leukocytes of the rumen fluid and demonstrated that they partly derive from saliva. Next, we carried out a field survey of innate immunity in rumen fluids of 128 cows from 12 dairy farms, along with clinical inspections, assessment of milk yield, rumen pH, volatile fatty acids (VFA) and major inflammo-metabolic parameters. Significant statistical correlations were found between immune markers in rumen fluids and biochemical parameters. A significant negative correlation was found in rumen between CD45 gene expression (leukocyte infiltration) and pH level. B cells were the most frequent mononuclear leukocyte population in the rumen liquor and their infiltration was negatively affected by low ruminal pH and high concentrations of VFA. Moreover, total Ig and IgM in rumen fluids were negatively correlated with ruminal pH and positively correlated with uremia. Our data suggest that forestomach immune responses could be directed to "dangers" arising within the forestomach environment. The immune markers could integrate consolidated diagnostic parameters (e.g. rumen pH) and contribute to robust, early diagnosis of tricky digestive troubles of cattle.

The periparturient period is the most critical phase in the productive cycle of dairy cows and is characterized by impairment of the immune system. Our objective was to evaluate the effect of feeding ethyl-cellulose rumen-protected methionine (RPM) starting at d -28 from expected parturition through 60 d in milk on biomarkers of inflammation, oxidative stress, and liver function as well as leukocyte function. Sixty multiparous Holstein cows were used in a block design and assigned to either a control or the control plus ethyl-cellulose RPM (Mepron, Evonik Nutrition & Care GmbH). Mepron was supplied from -28 to 60 d in milk at a rate of 0.09% and 0.10% dry matter during the prepartum and postpartum period. That rate ensured that the ratio of Lys to Met in the metabolizable protein was close to 2.8:1. Blood samples from 15 clinically healthy cows per treatment were collected at d -30, -14, 1, 7, 21, 30, and 60 and analyzed for biomarkers of liver function, inflammation, and oxidative stress. Neutrophil and monocyte function in whole blood was measured in vitro at -14, 1, 7, 21, and 30 d in milk. The statistical model included the random effect of block and fixed effect of treatment, time, and its interaction. Compared with control, ethyl-cellulose RPM increased plasma cholesterol and paraoxonase after parturition. Among the inflammation biomarkers measured, ethyl-cellulose RPM led to greater albumin (negative acute-phase protein) and lower haptoglobin than control cows. Although concentration of IL-1β was not affected by treatments, greater IL-6 concentration was detected in response to ethyl-cellulose RPM. Cows supplemented with ethyl-cellulose RPM had greater plasma concentration of ferric-reducing antioxidant power, β-carotene, tocopherol, and total and reduced glutathione, whereas reactive oxygen metabolites were lower compared with control cows. Compared with control, ethyl-cellulose RPM enhanced neutrophil phagocytosis and oxidative burst. Overall, the results indicate that ethyl-cellulose RPM supply to obtain a Lys-to-Met ratio of 2.8:1 in the metabolizable protein during the periparturient period and early lactation is an effective approach to help mitigate oxidative stress and inflammation as well as enhance liver and neutrophil function in dairy cows.

Pressure aimed at reducing the use of antibiotics in livestock is steadily increasing. In 2022, the prophylactic use of antibiotics for preventive purposes will be banned in the European Union (EU), including blanket therapy at dry-off. The objective of this study was to evaluate the short- and long-term effects of selectively treating cows with low somatic cell count (SCC) at dry-off using internal teat sealant with or without antibiotic therapy on udder health, milk production, metabolic, and inflammatory conditions through the next lactation. Fifteen Holstein dairy cows without intramammary infections and with SCC less than 200×103 cells/mL at dry-off were enrolled in the study. Cows were abruptly dried off and treated either with antibiotic plus teat sealant (AB) or with teat sealant only (TS). Milk and blood samples were collected on scheduled days from 10 days before dry-off to 28 days after calving. Milk composition and both inflammatory and metabolic profiles were assessed. Fertility and milk production were recorded during the previous and subsequent lactation. Rumination time was monitored from three weeks before dry-off to four weeks after calving. Data were analyzed with PROC MIXED and PROC GLM of SAS software. Total milk production, reproductive performance, rumination time, and mastitis incidence did not differ between groups. Milk yield during the first 120 days after calving was not affected by treatment. Milk composition and SCC were not affected during the first month. Compared with AB, TS had lower plasma calcium at -47 days from calving, gamma-glutamyl transferase at –50, –47, and –42, tocopherol at –65, –50, and –47, and alkaline phosphatase at 3 days from calving. Overall, both metabolic and inflammatory statuses were similar between AB and TS cows with only small transient differences. With the perspective of reducing antibiotic usage in dairy farms, internal teat sealant could be used alone in healthy cows with low SCC with no relevant effects on udder health and immunometabolic profile in the subsequent lactation.

Johne's disease is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratubercolosis (MAP) which affects ruminants worldwide and has a significant economic impact. MAP has also been associated with human Crohn's disease, although this connection is not well established. MAP is highly adapted for survival within host macrophages and prevents macrophage activation, blocks phagosome acidification and maturation, and attenuates presentation of antigens to the immune system. The consequence is a very long silent infection before clinical signs are observed. The present work examined the transcriptome of bovine monocyte-derived macrophages (MDM) infected with the L1 strain of MAP at 2h, 6h and 24h post infection using RNA-seq. Pathway over-representation analysis of genes differentially expressed between infected vs. control MDM identified that immune related pathways were affected. Genes belonging to the cytokine-cytokine receptor interaction pathway and members of the JAK-STAT pathway, which is involved in the regulation of immune response, were up-regulated. However, in parallel inhibitors of immune functions were activated, including suppressor of cytokine signaling (SOCS) and cytokine-inducible SH2-containing protein (CISH), which most likely suppresses IFNγ and the JAK/STAT signaling cascade in infected MDM, which may favour MAP survival. After exposure, macrophages phagocytise pathogens, activate the complement cascade and the adaptive immune system through the antigen presentation process. However, data presented here suggest that genes related to phagocytosis and lysosome function are down regulated in MAP infected MDM. Genes of MHC class II and complement pathway were also down-regulated. This study therefore shows that MAP infection is associated with changes in expression of genes related to the host immune response that may affect its ability to survive and multiply inside the host cell.