Validation of VHH-Binding Proteins as a Dietary Alternative to Pharmacological Zinc Oxide for the Control of Post-Weaning Diarrhoea in Piglets

Post-weaning diarrhoea remains a major health and production challenge in pig farming, and effective alternatives to pharmacological zinc oxide are needed. This study evaluated bivalent VHH constructs as a potential dietary alternative to pharmacological zinc oxide under both controlled experimental and commercial production conditions. In Trial 1, 96 weaned piglets were orally challenged with enterotoxigenic Escherichia coli F4+ and received either a control diet, zinc-oxide-supplemented diet, or diet supplemented with bivalent VHH constructs. In Trial 2, 528 piglets were evaluated in a commercial nursery barn using the same dietary groups. In Trial 1, VHH supplementation improved post-challenge growth performance, reduced faecal EHEC counts and increased the lactobacilli-to-EHEC ratio, confirming previous evidence obtained under controlled conditions. Importantly, similar responses were observed under commercial conditions in Trial 2, where VHH-supplemented piglets showed improved faecal scores, higher average daily gain and greater final body weight. Quantile analysis further indicated that the positive response extended to the lower tail of the distribution of pen-level performance. These findings extend previous experimental evidence and demonstrate the efficacy of VHH supplementation under commercial production conditions, supporting its use as a nutritional alternative to pharmacological ZnO during the post-weaning period.