An alternative ZnO with large specific surface area: Preparation, physicochemical characterization and effects on growth performance, diarrhea, zinc metabolism and gut barrier function of weaning piglets.

High-dose ZnO is widely used to prevent diarrhea and promote growth of weaning piglets, which has led to serious problems of animal toxicity, bacterial resistance and environmental pollution. In this study, a novel alternative ZnO (AZO) was prepared and its physicochemical properties were characterized. Animal experiments were further conducted to evaluate the effects of the ZnO forms, the dose of AZO and the combinations with AZO on the growth performance, diarrhea, zinc metabolism and gut barrier function of weaning piglets. The results showed that the AZO, compared with ordinary ZnO (OZO), nano ZnO (NZO) and porous ZnO (PZO), had the largest surface area and reduced the release of Zn into the gastric fluid. AZO showed better antibacterial activity on Escherichia coli K88, Staphylococcus aureus and Salmonella enteritidis but lower cytotoxicity on porcine intestinal epithelial cells. Animal experiments suggested that low-dose AZO, NZO and PZO (300 mg/kg) improved growth performance and reduced diarrhea in weaning piglets as well as high-dose OZO (3000 mg/kg). Notably, low-dose AZO had the lowest diarrhea incidence. Additionally, low-dose AZO in combination with probiotics improved digestibility and digestive enzyme activities. Low-dose AZO in combination with probiotics also upregulated the expression of the intestinal zinc transporter proteins ZIP4 and DMT1, increased zinc bioavailability, reduced faecal zinc emissions, and avoided zinc overload in the liver and oxidative damage caused by high-dose ZnO. Moreover, low-dose AZO in combination with probiotics improved the gut barrier function of weaning piglets by promoting the expression of tight junction proteins, mucins and antimicrobial peptides and increasing gut microbiota diversity and beneficial Lactobacillus. This study proposed a novel strategy to replace high-dose ZnO and antibiotics with low-dose AZO and probiotics in weaning piglets, which effectively improved growth performance and prevented diarrhea while reducing animal toxicity, bacterial resistance, heavy metal residues and zinc emission pollution.