Heat stress and dietary organic acid and pure botanical supplementation alter the metabolome of lactating dairy cows.

We previously demonstrated that heat stress (HS) evolves with increased gastrointestinal permeability (GP) and dietary organic acid and pure botanical (OA/PB) supplementation improved milk production of HS cows. Because the metabolome can be altered with increased GP, our objective was to identify metabolites that are related to GP and milk production in HS cows supplemented with OA/PB. Forty-six Holstein cows were enrolled in a study with a completely randomized design. After 7 d of acclimation in thermoneutrality (temperature-humidity index [THI] 68), cows were assigned to 1 of 4 groups: thermoneutral conditions (TN-Con, n = 12), HS conditions (HS-Con, n = 12; diurnal THI 74 to 82), TN conditions pair-fed to match HS-Con (TN-PF, n = 12), or HS fed OA/PB top-dress (HS-OAPB, n = 10) for 14 d. GP was assessed with an oral Cr-EDTA challenge. Samples of liver and rumen fluid were collected on d 12 and plasma and cecal contents were collected on d 14. Metabolome profiles were assessed with untargeted metabolomics using quadrupole time-of-flight mass spectrometry. Means were analyzed using a mixed model with a false discovery rate (FDR) correction applied. Correlation between metabolites, production and GP was assessed with Pearson correlations. HS-Con had higher relative abundance (RA) of plasma and hepatic lysophosphatidylcholines (LPC; e.g., LPC-16:1 and −18:0), ruminal aspartate, and hepatic and cecal glutamate, relative to all treatments (FDR <0.01); and these metabolites were negatively correlated with milk yield and energy-corrected milk yield (ECM; r = −0.34 to −0.68; P < 0.05). While Met was negatively correlated with GP (r = −0.36, P = 0.02) and positively correlated with ECM (r = 0.42, P < 0.01), we observed higher Met RA in HS-OAPB, relative to HS-Con (FDR <0.01). HS-OAPB had reduced RA of hepatic palmitate, relative to HS-Con (FDR <0.01); and importantly, hepatic palmitate was strongly correlated with ECM (r = −0.61, P < 0.01) and moderately with GP (r = 0.31, P = 0.04). Changes in the metabolome of HS cows are associated with reduced milk production and increased GP.