In-feed provision of binding proteins sustains piglet gut health and mitigates ETEC-induced post-weaning diarrhea

Abstract Background Post-weaning diarrhea (PWD) in piglets, often caused by F4+ enterotoxigenic Escherichia coli (ETEC), poses significant challenges in pig production. Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistan...

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Main Authors: Jiajia Xu, Melania Andrani, Rikke Brødsgaard Kjærup, Tina Sørensen Dalgaard, Carsten Eriksen, Andreas Hougaard Laustsen, Susanne Brix, Sandra Wingaard Thrane, Nuria Canibe
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Animal Science and Biotechnology
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Online Access:https://doi.org/10.1186/s40104-025-01209-6
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author Jiajia Xu
Melania Andrani
Rikke Brødsgaard Kjærup
Tina Sørensen Dalgaard
Carsten Eriksen
Andreas Hougaard Laustsen
Susanne Brix
Sandra Wingaard Thrane
Nuria Canibe
author_facet Jiajia Xu
Melania Andrani
Rikke Brødsgaard Kjærup
Tina Sørensen Dalgaard
Carsten Eriksen
Andreas Hougaard Laustsen
Susanne Brix
Sandra Wingaard Thrane
Nuria Canibe
author_sort Jiajia Xu
collection DOAJ
description Abstract Background Post-weaning diarrhea (PWD) in piglets, often caused by F4+ enterotoxigenic Escherichia coli (ETEC), poses significant challenges in pig production. Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability. This study investigates the application of bivalent heavy chain variable domain (VHH) constructs (BL1.2 and BL2.2) targeting ETEC virulence factors, administered in feed to mitigate ETEC-induced PWD in weaned piglets. Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4+ ETEC in challenged piglets. Pelleted feed containing VHH constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine. Additionally, the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group, including neutrophils, and ameliorated the acute phase protein response after challenge. Notably, even at low feed intake immediately after weaning, VHH constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea. Conclusions Our findings demonstrated that using VHH constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD, by reducing F4+ ETEC gut colonization and supporting gut barrier function of weaned piglets. The high stability of these VHH constructs supports their incorporation into industrial feed manufacturing processes, offering a more sustainable preventive strategy compared to traditional antimicrobial interventions, which could contribute to sustainable farming practices.
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spelling doaj-art-ccc1e1a73ca44838bbd7dde1007fd6012025-08-20T02:30:43ZengBMCJournal of Animal Science and Biotechnology2049-18912025-06-0116112110.1186/s40104-025-01209-6In-feed provision of binding proteins sustains piglet gut health and mitigates ETEC-induced post-weaning diarrheaJiajia Xu0Melania Andrani1Rikke Brødsgaard Kjærup2Tina Sørensen Dalgaard3Carsten Eriksen4Andreas Hougaard Laustsen5Susanne Brix6Sandra Wingaard Thrane7Nuria Canibe8Department of Animal and Veterinary Sciences, Aarhus UniversityDepartment of Veterinary Science, University of ParmaDepartment of Animal and Veterinary Sciences, Aarhus UniversityDepartment of Animal and Veterinary Sciences, Aarhus UniversityDepartment of Biotechnology and Biomedicine, Technical University of DenmarkDepartment of Biotechnology and Biomedicine, Technical University of DenmarkDepartment of Biotechnology and Biomedicine, Technical University of DenmarkBactolife A/SDepartment of Animal and Veterinary Sciences, Aarhus UniversityAbstract Background Post-weaning diarrhea (PWD) in piglets, often caused by F4+ enterotoxigenic Escherichia coli (ETEC), poses significant challenges in pig production. Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability. This study investigates the application of bivalent heavy chain variable domain (VHH) constructs (BL1.2 and BL2.2) targeting ETEC virulence factors, administered in feed to mitigate ETEC-induced PWD in weaned piglets. Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4+ ETEC in challenged piglets. Pelleted feed containing VHH constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine. Additionally, the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group, including neutrophils, and ameliorated the acute phase protein response after challenge. Notably, even at low feed intake immediately after weaning, VHH constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea. Conclusions Our findings demonstrated that using VHH constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD, by reducing F4+ ETEC gut colonization and supporting gut barrier function of weaned piglets. The high stability of these VHH constructs supports their incorporation into industrial feed manufacturing processes, offering a more sustainable preventive strategy compared to traditional antimicrobial interventions, which could contribute to sustainable farming practices.https://doi.org/10.1186/s40104-025-01209-6Antimicrobial alternativesBinding proteinsEnterotoxigenic E. coliFeed additiveGut healthPiglets
spellingShingle Jiajia Xu
Melania Andrani
Rikke Brødsgaard Kjærup
Tina Sørensen Dalgaard
Carsten Eriksen
Andreas Hougaard Laustsen
Susanne Brix
Sandra Wingaard Thrane
Nuria Canibe
In-feed provision of binding proteins sustains piglet gut health and mitigates ETEC-induced post-weaning diarrhea
Journal of Animal Science and Biotechnology
Antimicrobial alternatives
Binding proteins
Enterotoxigenic E. coli
Feed additive
Gut health
Piglets
title In-feed provision of binding proteins sustains piglet gut health and mitigates ETEC-induced post-weaning diarrhea
title_full In-feed provision of binding proteins sustains piglet gut health and mitigates ETEC-induced post-weaning diarrhea
title_fullStr In-feed provision of binding proteins sustains piglet gut health and mitigates ETEC-induced post-weaning diarrhea
title_full_unstemmed In-feed provision of binding proteins sustains piglet gut health and mitigates ETEC-induced post-weaning diarrhea
title_short In-feed provision of binding proteins sustains piglet gut health and mitigates ETEC-induced post-weaning diarrhea
title_sort in feed provision of binding proteins sustains piglet gut health and mitigates etec induced post weaning diarrhea
topic Antimicrobial alternatives
Binding proteins
Enterotoxigenic E. coli
Feed additive
Gut health
Piglets
url https://doi.org/10.1186/s40104-025-01209-6
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