Aspects of transition cow metabolomics—Part I: Effects of a metaphylactic butaphosphan and cyanocobalamin treatment on the metabolome in liver, blood, and urine in cows with different liver metabotypes

Abstract

Dairy cows in modern production systems are at risk to develop metabolic disorders during the transition period. Reasons for individual differences in susceptibility, as well as the underlying pathomechanisms, are still only partially understood. The development of metaphylactic treatment protocols is needed. In this context, an on-farm prospective 3-fold blinded randomized study involving 80 German Holstein cows was performed throughout 1 yr. The trial involved a thorough recording of the production and clinical traits, clinical chemistry, and liver biopsies and blood and urine sampling at d 14 (mean: 12 d, range: 1-26 d) antepartum (AP), and d 7 (7, 4-13) and 28 (28, 23-34) postpartum (PP) for metabolomics analyses. Two groups received a treatment with butaphosphan and cyanocobalamin (BCC) at either the dosage recommended by the manufacturer or the double dosage (5 or 10 mL/100 kg of body weight 10% butaphosphan and 0.005% cyanocobalamin (Catosal, Bayer Animal Health), n = 20 in each group, parity: 4.2 ± 2.0 and 3.4 ± 1.3, respectively (mean ± SD)] and one group a placebo treatment (NaCl 0.9%, n = 40, parity: 4.0 ± 1.9). The animals were treated at 6 time points (7, 6, and 5 d AP, and 1, 2, and 3 d PP) via intravenous injection. Mass spectroscopy-based targeted metabolomics analysis of blood plasma and liver samples were performed using the AbsoluteIDQ p180 kit (Biocrates Life Sciences), whereas the urine samples were analyzed by nuclear magnetic resonance

Aspects of transition cow metabolomics—Part III: Alterations in the metabolome of liver and blood throughout the transition period in cows with different liver metabotypes

“…The Materials and Methods are described in Part I (Schären et al, 2021). In the following section, a brief summary is given.…”

“…Three different metabotypes were identified in a follow-up analysis based on their metabolic alterations in the liver over the course of the transition period [based on patterns observed in the partial least squares discriminant analysis (PLS-DA) plots of the liver metabolome, A = medium, B = minor, C = large alterations in the liver metabolic profiles between AP and PP status, details in Part I; Schären et al, 2021]. It was further discovered that the metabotypes corresponded with the time the animals entered the study: animals calving in either period A: November 23, 2015to February 6, 2016, B: February 7 to May 31, 2016 (n = 28), or C: June 1 to December 3, 2016 (n = 37).…”

“…Metabotype B animals were characterized by: lower milk protein percentage and higher milk fat percentage, higher AP and stronger peripartum decrease in BCS, higher risk to be diseased, and higher PP blood bilirubin, fatty acids, gamma-glutamyltransferase, and triglyceride levels. Reasons for this increased lipomobilization and clinical sequelae presumably lie in a decreased grass silage quality fed in this period (elaborated in the discussion of Part I; Schären et al, 2021).…”

“…Permutation test were performed to validate the PLS-DA models and tested for over-fitting as described in Sun et al (2014). In this manuscript only valid models were used, and the respective permutations tests were added to the Supplemental Files of Part I (https: / / nbn -resolving .org/ urn: nbn: de: bsz: 15 -qucosa2 -744120; summarizing all multivariate models from Part I and Part III; Schären et al, 2021).…”

“…In Part I (Schären et al, 2021) of the study, the identification of the metabotypes and their differences on production and clinical levels (clinical traits and chemistry), as well as the effects of a metaphylactic treatment with BCC on the clinical and metabolomic levels, are described. Part II (Pietsch et al, 2021) illustrates the liver histopathological alterations across the transition period and their relation to the metabotypes and which changes were affected by a metaphylactic BCC treatment.…”