Pharmacological Zinc Oxide Reduces F18 Enterotoxigenic Escherichia coli Attachment in Weanling Pigs

Abstract Zinc oxide at pharmacological concentrations can enhance nursery pig growth performance, improve intestinal health, and reduce post-weaning diarrhea. However, the mechanisms underlying these benefits remain unclear. This study investigated the mode of action by which zinc oxide improves intestinal health and growth performance in nursery pigs challenged with F18 enterotoxigenic Escherichia coli (ETEC). A total of 196 newly weaned pigs Camborough 1050 × 337 (PIC, Hendersonville, TN) were utilized in a 2x2 factorial design consisting of corn–soybean meal diets containing either 120 ppm zinc (CON) or 3,000 ppm zinc from zinc oxide (ZNO), and non-challenged (NC; 6.11 ± 1.0 kg BW) or F18 ETEC-challenged (ETEC; 6.08 ± 1.1 kg BW). Pens were balanced for α-(1,2) fucosyltransferase (FUT1) genotype and randomly assigned to diets. Feed was provided ad libitum in two phases (10 and 28 days). On day 10 day post-inoculation (dpi) 0, ETEC pens were orally inoculated with 5 mL of a 2.2 × 109 cfu/mL F18 ETEC culture. Pig BW and feed disappearance were recorded on dpi -10, 0, 5, 7, 12, 19, and 28 to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F). Pooled pen fecal dry matter (DM) and F18 and LT gene abundance (qPCR) were measured on dpi –1, 3, 5, 7, 9, 11, 14, and 20. On dpi 5 and 7, one FUT1 heterozygous (A/G) pig per pen was euthanized and fixed ileal tissues were evaluated for histomorphology and F18 attachment (in situ hybridization). Pen served as the experimental unit, and data were analyzed for main effects and interactions of diet and ETEC challenge, with room included as a random effect. During the pre-inoculation period (dpi –10 to 0), ZNO pigs had greater ADG (P = 0.015) and ADFI (P = 0.036) compared with CON, while G:F was not affected. At dpi 28, ETEC-CON pigs had lower BW compared with ETEC-ZNO (18.6 vs. 22.9 kg; P = 0.007). Overall (dpi –10 to 28), a diet by challenge interaction was observed where ETEC-CON pigs exhibited reduced ADG compared to ETEC-ZNO (0.32 vs. 0.44 kg/d; P = 0.001). At dpi 5, ileal F18 ETEC attachment was greater in the ETEC-CON pigs than ETEC-ZNO, NC-CON, and NC-ZNO (0.03%, 0.02%, and 0.06%, respectively; P = 0.012). By dpi 7, ileal F18 attachment remained higher in ETEC pigs than NC (P = 0.001), but the overall magnitude of staining was reduced compared with dpi 5. Fecal consistency improved from dpi –1 to 20, with fecal DM tending to be lower in ETEC-CON pens compared with all other treatments (P = 0.089). Overall, a major mode of action was zinc oxide’s ability to reduce F18 ETEC adherence to the intestinal epithelium. Subsequently, pharmacological ZNO improved growth performance and fecal consistency in the presence of an ETEC challenge.