FORESTRY BYPRODUCTS AS NOVEL THERAPEUTICS FOR PARASITE CONTROL IN LIVESTOCK

林业副产品作为控制牲畜寄生虫的新疗法

• 批准号: BB/X017397/1
• 负责人: Spiridoula Athanasiadou
• 金额: $ 36.66万
• 依托单位: Scotland's Rural College
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX017397%2F1
• 关键词: FORESTRY; BYPRODUCTS; NOVEL; THERAPEUTICS; PARASITE

"Sustainable food production" - the process by which we feed the ever-growing world population - is at the top of every agenda. To deliver sustainable food production, it is essential that livestock live in excellent conditions and are healthy throughout their lives. Gastrointestinal parasitism is a direct challenge to this due to negative consequences on animal health and welfare and on the environment. In addition, parasitic disease directly results in a 30% increase in greenhouse gas emissions, which exacerbates climate change and so also threatens food production.Drugs are often used to treat parasitic disease, but resistance to the drugs that kill these types of parasites is now widespread throughout the world, with a prevalence of nearly 100% in many countries. This leads to worldwide costs for food soaring by billions of pounds. In other words, the continuous use of drugs in livestock over the last 60 years has been positive in that it has increased livestock productivity and profitability, but the positive effects of the current generation of drugs (known as anthelmintics) is under threat due to global challenges, including antimicrobial resistance, climate change and maintenance of biodiversity. This project therefore directly addresses the impact that parasitism has on sustainable food production. It does this by using a low-value by-product for the UK's forestry industry and by incorporating this by-product into a next generation natural dietary supplement for livestock.Natural compounds extracted from plants (often called plant secondary metabolites (PSM)), are known to disrupt the life cycle of parasitic nematodes both in the animal and in the environment. PSM can therefore act as anthelmintics, controlling the disease these parasites cause. However, using a single pure PSM is expensive. Attention has therefore turned to PSM-rich extracts that contain a complex mixture of PSM as this is cheaper. However, this approach is hampered by large variations in the PSM content. Variability in PSM-content across different extracts leads to irreproducible biological activity. Whilst studies have demonstrated the anthelminitic effects of individual PSMs and/or plant extracts, the use of PSM-rich extracts is still understudied. There are insufficient reports on the effect on biological activity of combinations of PSMs or the contributions of individual PSM. Repeatable production of extracts (and thus consistent biological activity) requires a more detailed understanding of both the chemistry contained within PSM-extracts and the biological interactions of the active compounds in PSM-extracts with the parasites.Tree bark is particularly rich in antiparasitic PSM and it is very likely that the UK forestry industry creates enough bark waste to treat the UK livestock population, so long as the PSM-extract is administered at key times of parasite susceptibility. This project therefore brings together the forestry, livestock and bioprocessing industries with academic experts in parasitology, chemical biology, analytical and statistical analysis to understand the full extent of the interaction of the parasites with the tree bark extracts. In doing so, it will identify, and isolate compounds present in the bark extracts that demonstrate anthelmintic activity. This will enable the creation of an "Activity Index" - a tool to predict the anthelmintic activity of any future bark extract. This Activity Index will subsequently guide the characterisation of future large scale bark extracts, predicting their anthelmintic potential and optimise their inclusion in parasite control strategies. To achieve this, we will identify and test compounds for their presence in bark extracts and their anthelmintic activity. We will select potentially bioactive compounds on literature reports, preliminary evidence already available to us from previous work and novel work described in this proposal.

“可持续粮食生产”——我们养活不断增长的世界人口的过程——是每个议程的首要任务。为了实现可持续的粮食生产，牲畜必须生活在良好的条件下并终生保持健康。由于对动物健康和福利以及环境产生负面影响，胃肠道寄生是对此的直接挑战。此外，寄生虫病直接导致温室气体排放增加30%，加剧气候变化，也威胁粮食生产。药物通常用于治疗寄生虫病，但目前对杀死此类寄生虫的药物的耐药性该病在世界范围内广泛传播，许多国家的患病率接近 100%。这导致全球食品成本飙升数十亿英镑。换句话说，过去 60 年来对牲畜持续使用药物是积极的，因为它提高了牲畜的生产力和盈利能力，但当前这一代药物（称为驱虫药）的积极作用正受到威胁，因为全球挑战，包括抗菌素耐药性、气候变化和生物多样性的维护。因此，该项目直接解决寄生对可持续粮食生产的影响。它通过使用英国林业工业的低价值副产品并将该副产品纳入下一代牲畜天然膳食补充剂来实现这一目标。从植物中提取的天然化合物（通常称为植物次生代谢物（PSM）），已知会破坏动物和环境中寄生线虫的生命周期。因此，PSM 可以充当驱虫药，控制这些寄生虫引起的疾病。然而，使用单个纯 PSM 的成本很高。因此，人们的注意力转向了富含 PSM 的提取物，其中含有 PSM 的复杂混合物，因为这种提取物更便宜。然而，这种方法受到 PSM 内容的巨大变化的阻碍。不同提取物中 PSM 含量的差异会导致生物活性无法重现。虽然研究已经证明了单独的 PSM 和/或植物提取物的驱虫作用，但富含 PSM 的提取物的使用仍有待研究。关于 PSM 组合对生物活性的影响或单个 PSM 的贡献的报道还不够。提取物的可重复生产（以及一致的生物活性）需要更详细地了解 PSM 提取物中所含的化学成分以及 PSM 提取物中的活性化合物与寄生虫的生物相互作用。树皮特别富含抗寄生虫 PSM 和只要在寄生虫易感的关键时期施用 PSM 提取物，英国林业工业就很可能产生足够的树皮废物来治疗英国的牲畜。因此，该项目汇集了林业、畜牧业和生物加工业以及寄生虫学、化学生物学、分析和统计分析方面的学术专家，以了解寄生虫与树皮提取物相互作用的全部范围。在此过程中，它将识别并分离树皮提取物中存在的具有驱虫活性的化合物。这将能够创建“活性指数”——一种预测任何未来树皮提取物的驱虫活性的工具。该活性指数随后将指导未来大规模树皮提取物的表征，预测其驱虫潜力并优化其在寄生虫控制策略中的应用。为了实现这一目标，我们将鉴定并测试树皮提取物中化合物的存在及其驱虫活性。我们将根据文献报告、我们从之前的工作和本提案中描述的新颖工作中已经获得的初步证据来选择潜在的生物活性化合物。