Stabilisation of the gut microbiota and reduction of ETEC proliferation in piglets using two bivalent VHH constructs

Post-weaning diarrhea (PWD) in piglets presents a widespread problem in industrial pig production and is caused by enterotoxigenic E. coli (ETEC) strains. Current solutions, such as antibiotics and medicinal zinc oxide, are unsustainable and face bans, resulting in a dire need for novel solutions. Thus, in this study, we propose and evaluate a protein-based feed additive, comprising bivalent heavy chain variable domain (VHH) constructs. We demonstrate in vitro that these constructs bind to ETEC toxins and fimbriae, whilst not affecting bacterial growth rate. Furthermore, in a pig study, we show that oral administration of these constructs after ETEC challenge reduced ETEC proliferation, and potentially stabilised the commensal microbiota when compared to challenged control piglets. These data suggest that such VHH constructs may find utility in industrial pig production as a feed additive for tackling ETEC and reducing the risk of PWD in piglet populations.