Feeding supplemental 25-hydroxyvitamin D3 increases serum mineral concentrations and alters mammary immunity of lactating dairy cows

Abstract

Objectives were to determine the effects of feeding supplemental 25-hydroxyvitamin D 3 [25(OH)D 3 ] on concentrations of vitamin D metabolites and minerals in serum, mammary immune status, and responses to intramammary bacterial infection in dairy cows. Sixty multiparous, pregnant lactating Holstein cows with somatic cell count <200,000/mL were blocked by days in milk and milk yield and randomly assigned to receive a daily top-dressed dietary supplement containing 1 or 3 mg of vitamin D 3 (1mgD or 3mgD), or 1 or 3 mg 25(OH) D 3 (1mg25D or 3mg25D) for 28 d (n = 15/treatment). Cows were kept in a freestall barn and fed a total mixed ration in individual feeding gates. Individual dry matter intake (DMI) and milk yield were recorded daily, and milk and blood samples were collected at 0, 7, 14, and 21 d relative to the start of treatment. At 21 d, cows fed 1mgD and 3mg25D received an intramammary challenge with Streptococcus uberis. Cows were observed for severity of mastitis, and blood and milk samples were collected every 12 h to measure inflammation. The 1mg25D and 3mg25D cows had greater serum 25(OH)D 3 concentrations at 21 d compared with 1mgD and 3mgD cows (62 ± 7, 66 ± 8, 135 ± 15, and 232 ± 26 ng/mL for 1mgD, 3mgD, 1mg25D, and 3mg25D, respectively). The 3mg25D cows had greater concentrations of Ca and P in serum at 21 d compared with other treatments (Ca = 2.38, 2.4, 2.37, and 2.48 ± 0.02 mM, 1.87, 1.88, and 2.10 ± 0.08 mM for 1mgD, 3mgD, 1mg25D, and 3mg25D, respectively). Yields of milk and milk components, DMI, body weight, and concentrations of 1,25-dihydroxyvitamin D and Mg in serum did not differ among treatments. Abundance of mRNA transcripts for interleukin-1β (IL1B) and inducible ni-tric oxide synthase (iNOS) in milk somatic cells before S. uberis challenge were increased in cows fed 25(OH) D 3 compared with cows fed vitamin D 3. Furthermore, IL1B, iNOS, β-defensin 7, and β-defensin 10 in milk somatic cells increased as concentrations of 25(OH)D 3 increased in serum. Cows fed 3mg25D had less severe mastitis at 60 and 72 h after challenge with S. uberis compared with cows fed 1mgD. Concentrations of bacteria, somatic cells, and serum albumin in milk after challenge did not differ between treatments; however, an interaction between treatment and day was detected for lactate dehydrogenase in milk. Expression of adhesion protein CD11b on milk neutrophils after the S. uberis challenge was greater among 3mg25D cows compared with 1mgD cows. Transcripts of CYP24A1 and iNOS in milk somatic cells during mastitis also were greater in 3mg25D cows compared with 1mgD cows. Feeding 25(OH)D 3 increased serum 25(OH)D 3 more effectively than supplemental vitamin D 3 , resulting in increased serum mineral concentrations, increased expression of vitamin D-responsive genes, and altered immune responses to intramammary bacterial challenge.

Connecting Metabolism to Mastitis: Hyperketonemia Impaired Mammary Gland Defenses During a Streptococcus uberis Challenge in Dairy Cattle

“…We speculate that this is likely due to differences in challenge models. Specifically, LPS would stimulate a rapid immune response within a few hours following challenge, whereas a live S. uberis challenge would slowly progress over the course of days, as seen in the present study as well as past studies (21,36). Potentially, a longer BHB infusion time was needed to reveal differences in diapedesis when using a S. uberis challenge model.…”

Vitamin D signaling increases nitric oxide and antioxidant defenses of bovine monocytes

“…R ecent reports have documented positive effects of 25-hydroxyvitamin D 3 [25(OH)D 3 ] for protection against uterine and mammary infections in dairy cows (Lippolis et al, 2011;Martinez et al, 2018;Poindexter et al, 2020). Concentrations of 25(OH)D 3 in serum of dairy cows during the postpartum period, a time when cows are at greatest risk of disease, are lower compared with those during prepartum or mid lactation (Nelson et al, 2016;Holcombe et al, 2018).…”

“…In particular, 1,25(OH) 2 D 3 elicits a robust nitric oxide (NO) response in bovine monocytes and macrophages, which enhances killing of Mycobacteria bovis by macrophages (García-Barragán et al, 2018). Intramammary and dietary vitamin D treatments also increased abundance of transcripts for inducible nitric oxide synthase (NOS2) in immune cells of the mammary glands of cows (Merriman et al, 2017;Poindexter et al, 2020). However, NO production by immune cells may increase oxidation of host cell membranes and proteins and, if not balanced by protective antioxidant mechanisms, lead to tissue damage (Shi et al, 2018).…”

A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle

“…For instance, polymorphisms in GC have been shown to cause vitamin D deficiency and inflammatory diseases in humans [25]. Moreover, a therapeutic use of vitamin D in lactating, CMinfected cows reduced inflammation, implying a link between vitamin D and inflammation [26][27][28]. Yet, the GWAS lead SNP was not associated with GC expression or alternative transcription, leaving the functional mechanism elusive [13].…”