Canada_IPAP: Impact of alternative nutrition management on AMR burden, transmission and trends in dairy cattle.

抗菌素耐药性（Antimicrobial resistance， AMR）是指微生物抵抗抗菌素治疗的能力。这是一个紧迫的全球公共卫生威胁，对人类和动物健康有直接影响。抗菌素耐药性带来了沉重的经济负担，因为治疗费用更高，疾病导致生产力下降。滥用和过度使用抗微生物药物是耐药病原体发展的主要驱动因素，包括在畜牧生产中。在奶牛中，对治疗人类病原体很重要的抗生素，如青霉素、头孢菌素和四环素，也广泛用于治疗乳腺炎。此外，牲畜中与抗菌素耐药性相关的细菌可通过直接接触，或通过与土壤、水和粪便等环境的接触，或通过食品加工过程中的交叉污染（称为水平基因转移）传播给人类。最近的研究表明，日粮对奶牛体内抗微生物药物耐药性基因（ARGs）的存在和类型有重要影响。奶牛ARGs的脱落和传播也可归因于与饲料有关的胃肠道微生物的应激反应和有害细菌的感染。这是一个重要的发现，因为饲养管理和饮食改变对代谢适应至关重要，特别是在过渡期奶牛中。奶牛的过渡期是产犊前3周至产犊后3周之间的时间。这一时期对奶牛的健康、生育力和生产力至关重要，因为奶牛经历了剧烈的新陈代谢和变化，使它们极易感染疾病。因此，他们在这一时期的饮食和能量摄入对于提高他们的免疫力和预防传染病的高发非常重要，因为传染病可能导致抗生素的使用增加，从而增加耐药性。很明显，营养变化为改善奶牛健康、减少抗生素使用和减少抗生素耐药性提供了最大的机会。因此，为了改善抗生素耐药性问题，同时促进动物健康，在乳制品行业使用非抗生素饲料补充剂越来越受欢迎。然而，这些饲料补充剂对抗菌素耐药性负担和传播的影响在很大程度上是未知的。这强调了基础研究的重要性，即饲料补充如何不仅有助于动物健康和免疫，还有助于抗微生物药物耐药性的负担和传播，特别是在乳制品行业，目前价值44亿英镑的市场价格。因此，在本研究中，我们将研究在过渡期奶牛中使用透乳作为饲料添加剂以改善动物健康的潜力，同时评估其对奶牛抗菌素耐药性负担的影响。牛奶渗透物是奶酪和酸奶生产过程中牛奶加工的主要副产品，它的干燥物有时被用来代替奶牛日粮中的淀粉。然而，由于与干燥和运输相关的成本，该产品的使用受到限制，因此，渗透牛奶总是供过于求。例如，2020年英国和加拿大分别倾倒了100万和3000万升牛奶。我们的目标是评估使用剩余的牛奶渗透（液体形式）的潜力，否则将被倾倒，作为饲料补充，以提高过渡奶牛的免疫力和健康。这使我们能够解决创建循环经济的问题。我们还将利用牛奶渗透来解决奶牛过渡时期饮食变化和喂养管理方面的知识空白，以及相应的对ARGs存在和传播的影响。

Antimicrobial resistance (AMR) is the ability of microorganisms to resist antimicrobial treatments. It is an urgent global public health threat with a direct impact on human and animal health. AMR carries a heavy economic burden due to higher costs of treatments and reduced productivity caused by sickness. Misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant pathogens, including in livestock production. In dairy cattle, antibiotics important in treating pathogens in humans such as penicillin, cephalosporin and tetracycline are also used extensively to treat mastitis.Furthermore, AMR associated bacteria in livestock can be shed and disseminated to humans via direct contact, or through contact with the environment such as soil, water and faecal material, or through cross-contamination during food processing through a process known as horizontal gene transfer. Recent research has shown that diet has important effects on the presence and types of antimicrobial resistance genes (ARGs) present in dairy cows. The shedding and dissemination of ARGs by dairy cows has also been attributed to stress response of gastrointestinal tract microorganisms in relation to diet, and infection by harmful bacteria. This is an important finding as feeding management and dietary change are crucial for metabolic adaptation especially in the transition dairy cows. The transition period in dairy cows is the time between 3 weeks before calving to 3 weeks after calving. This period is critical for the health, fertility, and productivity of dairy cows as cows go through drastic metabolic and changes which render them extremely vulnerable to diseases. Therefore, their diet and energy intake during this period is important to boost their immunity and prevent high incidences of infectious diseases which may lead to increased antibiotic use and thus increased resistance.It is clear that nutritional changes provide the largest opportunities for improving health, reducing antibiotic usage and reducing AMR in dairy cattle. And so, to ameliorate the problem of AMR whilst bosting animal health, the use of non-antibiotic feed supplementation is gaining traction in the dairy industry. However, the impact of these feed supplements on AMR burden and spread of is largely unknown. This emphasises the importance of fundamental research into how feed supplementation contributes to not only animal health and immunity but to AMR burden and transmission, specifically in the dairy industry, currently worth £4.4bn in market prices.Therefore, in this study, we will investigate potential of using milk permeate as a feed supplement in transition dairy cows to improve animal health while assessing the effect this will have on the AMR burden of dairy.Milk permeate, is a major by-product of milk processing for cheese and yogurt production Its dried is sometimes used to replace starches in dairy cow diets. However, the use of this product has been limited due to the cost associated with drying and transport and as such, there is always an oversupply of milk permeate. For example, >1M and 30M litres of milk was dumped in the UK and Canada respectively in 2020.We aim to assess the potential of using surplus milk permeate (in its liquid form), which would otherwise be dumped, as feed supplements to improve immunity and health for transition dairy cow. This allows us address of creating a circular economy. We will also address the gaps in knowledge regarding dietary change and feeding management using milk permeate and the corresponding effect on the presence and transmission of ARGs during the transition period of dairy cows.