Protecting the piglet gut microbiota against ETEC-mediated post-weaning diarrhoea using specific binding proteins

• Published in: NPJ biofilms and microbiomes Vol. 10; no. 1; p. 42
• Main Authors: Jenkins, Timothy Patrick, Ács, Norbert, Arendrup, Emma Wenzel, Swift, Abbie, Duzs, Ágnes, Chatzigiannidou, Ioanna, Pichler, Michael, Kittilä, Tiia, Peachey, Laura, Gram, Lone, Canibe, Nuria, Laustsen, Andreas Hougaard, Brix, Susanne, Thrane, Sandra Wingaard
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 02.05.2024; Nature Portfolio
• Subjects: Animal Feed; Animals; Antibiotics; Bacteria; Diarrhea; Diarrhea - microbiology; Diarrhea - prevention & control; Diarrhea - veterinary; Enterotoxigenic Escherichia coli; Escherichia coli Infections - microbiology; Escherichia coli Infections - prevention & control; Escherichia coli Infections - veterinary; Feces - microbiology; Feed additives; Gastrointestinal Microbiome; Intestinal microflora; Microbiota; Oral administration; Pili; Swine; Swine Diseases - microbiology; Swine Diseases - prevention & control; Weaning; Zinc oxide
• ISSN: 2055-5008; 2055-5008
• DOI: 10.1038/s41522-024-00514-8

Post-weaning diarrhoea (PWD) in piglets presents a widespread problem in industrial pig production and is often caused by enterotoxigenic E. coli (ETEC) strains. Current solutions, such as antibiotics and medicinal zinc oxide, are unsustainable and are increasingly being prohibited, resulting in a dire need for novel solutions. Thus, in this study, we propose and evaluate a protein-based feed additive, comprising two bivalent heavy chain variable domain (V H) constructs (V H-(GGGGS) -V H, BL1.2 and BL2.2) as an alternative solution to manage PWD. We demonstrate in vitro that these constructs bind to ETEC toxins and fimbriae, whilst they do no affect bacterial growth rate. Furthermore, in a pig study, we show that oral administration of these constructs after ETEC challenge reduced ETEC proliferation when compared to challenged control piglets (1-2 log units difference in gene copies and bacterial count/g faeces across day 2-7) and resulted in week 1 enrichment of three bacterial families (Prevotellaceae (estimate: 1.12 ± 0.25, q = 0.0054), Lactobacillaceae (estimate: 2.86 ± 0.52, q = 0.0012), and Ruminococcaceae (estimate: 0.66 ± 0.18, q = 0.049)) within the gut microbiota that appeared later in challenged control piglets, thus pointing to an earlier transition towards a more mature gut microbiota. These data suggest that such V H constructs may find utility in industrial pig production as a feed additive for tackling ETEC and reducing the risk of PWD in piglet populations.