Xu Jiajia, Andrani Melania, Kjærup Rikke Brødsgaard, Dalgaard Tina Sørensen, Eriksen Carsten, Laustsen Andreas Hougaard, Brix Susanne, Thrane Sandra Wingaard, Canibe Nuria
Department of Animal and Veterinary Sciences, Aarhus University, Tjele, Denmark.
Department of Veterinary Science, University of Parma, Parma, Italy.
J Anim Sci Biotechnol. 2025 Jun 2;16(1):78. doi: 10.1186/s40104-025-01209-6.
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 (VH) constructs (BL1.2 and BL2.2) targeting ETEC virulence factors, administered in feed to mitigate ETEC-induced PWD in weaned piglets.
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 VH 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, VH constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.
Our findings demonstrated that using VH 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 VH 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.
仔猪断奶后腹泻（PWD）通常由F4产肠毒素大肠杆菌（ETEC）引起，给养猪生产带来了重大挑战。由于对抗生素耐药性和环境可持续性的担忧日益增加，抗生素和氧化锌等传统解决方案面临越来越多的限制。本研究调查了针对ETEC毒力因子的二价重链可变区（VH）构建体（BL1.2和BL2.2）在饲料中的应用，以减轻ETEC诱导的断奶仔猪腹泻。
在粉料和颗粒饲料中添加BL1.2和BL2.2均显著降低了攻毒仔猪的腹泻发病率和F4 ETEC的粪便排出量。含有VH构建体的颗粒饲料通过维持小肠紧密连接蛋白闭合蛋白的水平，有助于保持肠道屏障完整性。此外，这些构建体将血液粒细胞计数维持在与未攻毒对照组相似的水平，包括中性粒细胞，并改善了攻毒后的急性期蛋白反应。值得注意的是，即使在断奶后立即采食量较低的情况下，VH构建体也通过减轻ETEC诱导的炎症和由此产生的腹泻来帮助维持仔猪健康。
我们的研究结果表明，使用VH构建体作为饲料添加剂可以作为一种有效的策略，通过减少F4 ETEC在肠道的定植并支持断奶仔猪的肠道屏障功能，来帮助管理与ETEC相关的PWD。这些VH构建体的高稳定性支持将它们纳入工业饲料生产过程，与传统的抗菌干预措施相比，提供了一种更可持续的预防策略，这有助于实现可持续养殖实践。
