Metabolomics of fescue toxicosis in grazing beef steers

• We applied high-resolution metabolomics (HRM) to plasma and urine of steers grazing toxic fescue.
• More than 13,000 and almost 21,000 unique metabolite features were detected in, respectively, the urine and plasma.
• The largest number of putative ergots alkaloids appeared after 2 or 14 days of grazing in, respectively, urine and plasma.
• Tryptophan and glycerophospholipid metabolism was perturbed by toxic fescue grazing.
• Novel plasma and urine metabolites, potential biomarkers of ergot alkaloid exposure and/or effect, were identified.

Fescue toxicosis (FT) results from consumption of tall fescue (Lolium arundinaceum) infected with an endophyte (Epichloë coenophiala) that produces ergot alkaloids (EA), which are considered key etiological agents of FT. Decreased weight gains, hormonal imbalance, circulating cholesterol disruption, and decreased volatile fatty acid absorption suggest toxic (E+) fescue-induced metabolic perturbations. Employing untargeted high-resolution metabolomics (HRM) to analyze E+ grazing-induced plasma and urine metabolome changes, fescue-naïve Angus steers were placed on E+ or non-toxic (Max-Q) fescue pastures and plasma and urine were sampled before, 1, 2, 14, and 28 days after pasture assignment. Plasma and urine catecholamines and urinary EA concentrations were also measured. In E+ steers, urinary EA appeared early and peaked at 14 days. 13,090 urinary and 20,908 plasma HRM features were detected; the most significant effects were observed earlier (2 days) in the urine and later (≥14 days) in the plasma. Alongside EA metabolite detection, tryptophan and lipid metabolism disruption were among the main consequences of E+ consumption. The E+ grazing-associated metabolic pathways and signatures described herein may accelerate development of novel early FT detection and treatment strategies.