PSV-1 Effect of Haemonchus contortus infection on plasma metabolome of periparturient Florida Cracker ewes.

Abstract Haemonchus contortus poses a significant threat to sustainable sheep production in the southern United States. The Florida Cracker, a heritage sheep breed, demonstrates remarkable resistance to parasites, yet the molecular mechanisms underlying this resistance remain poorly understood. The objective of this study was to assess the impact of H. contortus infection on the plasma metabolomic profile of Florida Cracker ewes during the peripartum period. A total of 20 pregnant Florida Cracker ewes were allocated into two groups: infected (INF, n=10) and control (CTL, n=10), at 90 days of pregnancy. Ewes were housed in pens with covered concrete floors of similar dimensions and characteristics, with ad libitum access to shelter, feed, and water. At 110 days of pregnancy, animals were dewormed with a combination of Cydectin (0.2 mg/kg) and Prohibit (8 mg/kg). A fecal egg reduction test confirmed the absence of parasite eggs prior to infection. At 120 days of pregnancy, the INF group was orally infected with 10,000 L3 larvae of H. contortus, while the CTL group received 3 mL of distilled water. Fecal egg counts (FECs) were measured at 0 and 3 hours, and at 2, 7, 14, and 28 days post-infection (dpi). Blood samples were collected by jugular venipuncture at the same time points, and plasma was extracted for targeted metabolomic analysis. Nuclear Magnetic Resonance (NMR) spectroscopy was employed to analyze 50 metabolites, including organic acids, amino acids, hexoses, lipids, and carnitines. The Shapiro-Wilk test assessed normality of the FEC data, and Box-Cox and logarithmic transformations (log(x+1)) were applied to the FEC values. The highest FEC (p < 0.05) was observed at 28 dpi in the INF group (3.11 ± 0.65), compared to the control group (0 ± 0). Significant differentially abundant metabolites were detected at 3hpi (1 downregulated metabolite), and at 7 (3 upregulated metabolites), 14 (16 downregulated and 6 upregulated metabolites), and 28dpi (14 upregulated metabolites). Key metabolic pathways identified included the metabolism of glycerolipids (3hpi), galactose (3hpi), purine (7dpi), pyrimidine (7dpi), propanoate (7dpi), biotin (7 and 14dpi), nitrogen (7dpi), glutathione (14dpi), primary bile acid biosynthesis (14dpi), pantothenate and CoA biosynthesis (14dpi), porphyrin (14dpi), lysine degradation (14dpi), lipoic acid (14 and 28dpi), beta-alanine (14 and 28dpi), glyoxylate and dicarboxylate (28dpi), and arginine and proline (28dpi). These pathways may be crucial in the ewe’s response to H. contortus infection during the peripartum period. Our findings indicate that H. contortus infection significantly alters the metabolomic profile of Florida Cracker ewes. Understanding these metabolic changes could help in the development of management strategies to mitigate gastrointestinal parasitism in sheep.