Intended and unintended consequences of the ZnO ban from pig diets on antimicrobial resistance, post-weaning diarrhoea and the microbiome.

在大多数国家，养猪通常在四周大时断奶。由于消化系统不成熟，仔猪特别容易受到肠道问题的影响，并且特别容易患上断奶后腹泻。断奶后腹泻会使受影响的动物感到痛苦和不适，并可导致死亡。康复后的仔猪通常健康状况较差，生长速度下降，影响福利和农场生产力。目前，胃肠道疾病是对英国和全球养猪系统可持续性的最大挑战，影响了全球一半以上的养猪户，给养猪业带来了巨大的成本。直到最近，断奶后腹泻都是通过在断奶后的饲料中添加氧化锌（ZnO）来控制的，这可以减少疾病并改善仔猪的结局。然而，由于担心氧化锌会导致抗生素耐药性的发展，最近在欧盟和英国都禁止了氧化锌的预防性使用。目前，还没有直接替代氧化锌的方法，而是一系列的实践。其中包括各种营养和管理方面的变化，可以根据每个农场的情况进行不同的应用。这引发了人们的担忧，即停用氧化锌后，断奶后腹泻可能会变得更加难以控制，对仔猪的健康和福利产生不利影响。尽管该部门做出了最大努力，但治疗更有可能需要依赖抗生素来治疗疾病和控制腹泻。因此，这给我们提出了一个难题：禁止氧化锌可能会增加农场的抗生素耐药性，因为农民在实践中可能需要使用更多的抗生素来治疗断奶后的患病仔猪。这些氧化锌提取的预期和意外后果是本提案的重点。在这项研究中，我们将在停药期间与生产商密切合作，调查氧化锌停药对仔猪健康的影响，并确定可能有帮助的措施。我们特别感兴趣的是氧化锌停用对农场致病细菌水平的影响，以及猪对抗生素耐药性的任何变化。为此，我们将从英国各地的少数商业牛群收集粪便样本，并比较氧化锌禁令前后的样本。我们已经从一些英国商业畜群中收集了禁令前的样本，作为这项拟议研究的先驱试点项目。对这些粪便样本的实验室分析将显示存在哪些致病细菌，并使我们能够寻找这些细菌特征的变化及其与疾病的关系，在氧化锌禁令前后。利用基因组测序技术，我们将寻找抗生素耐药标记物，看看这些标记物在停用氧化锌后是否都发生了变化。我们的研究结果将为英国农场在过渡期的仔猪健康状况提供一个“晴雨表”。我们还将研究氧化锌存在时猪健康肠道菌群的差异，以及是否可以鉴定出特定的有益细菌。我们将研究如何利用这些差异来开发替代饲料补充剂，例如可能有助于控制疾病和改善仔猪健康的“友好虫”补充剂。通过提供基于证据的信息，该项目将有助于抵消现有的不确定性，并在行业适应“零锌”的过程中为更广泛的讨论提供信息。反过来，这将有望导致养猪生产系统的发展，以可持续的方式处理管理断奶仔猪的挑战。

In most countries, farmed pigs are typically weaned at around four weeks of age. Young pigs are especially vulnerable to gut problems due to their immature digestive system and are particularly susceptible to a condition known as post-weaning diarrhoea. Post-weaning diarrhoea results in distress and discomfort in affected animals, and can lead to death. Recovered piglets often have poorer health and reduced growth, affecting welfare and farm productivity. Gastro-intestinal disease is currently the single most significant challenge to the sustainability of UK and global pig systems and affects more than half of pig farmers worldwide, at significant cost to the industry. Until recently, post-weaning diarrhoea was controlled by the addition of Zinc Oxide (ZnO) to feed after weaning, which reduced disease and improved piglet outcomes. However, due to concerns that ZnO contributes to the development of antibiotic resistance, prophylactic use of ZnO has recently been banned in both the EU and UK. At present, there is no direct replacement for ZnO, but rather a range of practices. These include a variety of nutritional and management changes, that may be variously applied according to the circumstances of each farm. This is prompting concern that by withdrawing ZnO, post-weaning diarrhoea may become more difficult to manage, with adverse consequences on piglet health and welfare. Despite the sector's best efforts, treatment will more likely need to rely on antibiotics to treat disease and manage diarrhoea. This, therefore, presents us with a conundrum: banning ZnO may possibly increase antibiotic resistance on farms, because farmers may need to use more antibiotics in practice, to treat sick piglets after weaning. These intended and unintended consequences of ZnO withdrawal are the focus of this proposal.In this study, we will work closely with producers over the withdrawal period to investigate the impact of ZnO withdrawal on piglet health and to identify measures that may help. In particular we are interested in the consequences of ZnO withdrawal on the levels of disease-causing bugs on farms and any changes in carriage of antibiotic resistance by pigs. We will do so by collecting dung samples from a small number of commercial herds across the UK and comparing samples from before and after the ZnO ban. We have already collected pre-ban samples from a number of UK commercial herds, in a precursor pilot project to this proposed study. Laboratory analysis of these dung samples will show which disease-causing bugs are present, and allow us to look for changes in the characteristics of these bugs and their association with disease, before and after the ZnO ban. Using genome sequencing technologies, we will look for antibiotic resistance markers, to see whether these all change after ZnO is withdrawn. Our findings will provide a 'barometer' of piglet health across UK farms during the transitional withdrawal period. We will also examine what differences are seen in the healthy gut microflora in pigs in the presence of ZnO and whether particular beneficial bacteria can be identified. We will investigate how we can exploit these differences to develop alternative feed supplements, such as "friendly bug" supplements that may help in the control of disease and improve piglet health.By providing evidence-based information, this project will help offset existing uncertainties and inform wider discussion as the sector adjusts to 'zero zinc.' This in turn would be expected to lead to the development of pig production systems that deal sustainably with the challenge of managing the post-weaned piglet.