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.

“可持续的粮食生产”-我们为不断增长的世界人口提供食物的过程-是每一项议程的首要任务。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，并在其一生中保持健康。由于对动物健康和福利以及对环境的负面影响，胃肠道寄生虫病是对这一点的直接挑战。此外，寄生虫病还直接导致温室气体排放量增加30%，加剧气候变化，从而威胁到粮食生产。寄生虫病通常使用药物来治疗，但对杀死这些类型的寄生虫的药物的耐药性现在在世界各地普遍存在，在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，在过去60年里，药物在牲畜中的持续使用是积极的，因为它提高了牲畜的生产力和盈利能力，但由于全球挑战，包括抗菌素耐药性，气候变化和维护生物多样性，当前一代药物（称为驱虫剂）的积极作用受到威胁。因此，该项目直接涉及寄生虫对可持续粮食生产的影响。它通过使用低价值的副产品为英国的林业产业，并将这种副产品纳入下一代天然饲料补充剂牲畜。从植物中提取的天然化合物（通常称为植物次级代谢产物（PSM）），已知破坏动物和环境中寄生线虫的生命周期。因此，PSM可以作为驱虫剂，控制这些寄生虫引起的疾病。然而，使用单一的纯PSM是昂贵的。因此，人们的注意力转向富含PSM的提取物，其含有PSM的复杂混合物，因为这更便宜。然而，这种方法受到PSM含量变化较大的阻碍。不同提取物中PSM含量的变异性导致不可重现的生物活性。虽然研究已经证明了单独的PSM和/或植物提取物的驱虫效果，但富含PSM的提取物的使用仍然研究不足。关于PSM组合对生物活性的影响或单个PSM的贡献的报告不足。提取物的可重复生产（和因此一致的生物活性）需要更详细地了解PSM提取物中所含的化学成分和PSM提取物中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，并且英国林业工业很可能产生足够的树皮废物来处理英国牲畜种群，只要PSM提取物在寄生虫易感性的关键时间施用即可。因此，该项目将林业、畜牧业和生物加工业与寄生虫学、化学生物学、分析和统计分析方面的学术专家聚集在一起，以了解寄生虫与树皮提取物相互作用的全部程度。在这样做的过程中，它将识别和分离树皮提取物中表现出驱虫活性的化合物。这将使创建一个“活动指数”-一个工具，以预测任何未来的树皮提取物的驱虫活性。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包含。为了实现这一目标，我们将确定和测试化合物的存在，树皮提取物和它们的驱虫活性。我们将选择潜在的生物活性化合物的文献报告，初步证据已经提供给我们从以前的工作和新的工作中描述的建议。