Gut health and immune function: the emerging role of gut microbiota in sustainable aquaculture

肠道健康和免疫功能：肠道微生物群在可持续水产养殖中的新兴作用

• 批准号: BB/M026604/1
• 负责人: Samuel Martin
• 金额: $ 26.54万
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM026604%2F1
• 关键词: Gut; health; immune; function; emerging

Global salmon production is ~1.5 million tonnes, with the UK currently at ~170,000 tonnes, which is worth approximately £1 billion to the UK economy annually. The majority of UK salmon aquaculture is located in Scotland and it represents over 40% of all Scottish food exports. Salmon farming is a growing food industry sector and Scotland has an ambition to increase its production by 50% by 2020. A major bottleneck of this growth is the provision of high quality feed that does not adversely impact salmon health. Salmon are piscivorous and traditional salmon feeds rely on wild sources of fish protein and fish oil that can no longer meet the demand from the global aquaculture industry. To overcome this shortfall, plant proteins and vegetable oils are being used to replace the wild sourced fish in aquaculture feeds. There are a number of major problems and constraints associated with this replacement, including reduced nutrient digestibility, gut inflammation, gut microbial imbalance and impaired resistance to pathogens. In this project, we will perform a series of experiments on Atlantic salmon and a zebrafish model fed with fish meal and plant-based diets to understand how these different diets shape the relationship between early intestinal development, immune function and gut microbiota. Zebrafish provide a unique model to study such a complex relationship because they are translucent and have established many advanced experimental techniques, including generation of germ-free larvae, live imaging of larvae colonised with fluorescent-tagged bacteria and generation of fish with fluorescent protein labelled inflammatory cells. None of these techniques are currently available for salmon or other farmed fish. By performing salmon feeding trial, we will establish how plant-based diets affect gut health (changes in gut morphology and gene expression profile) and how they change the abundance and diversity of gut microbiota. The diversity of gut microbiota will be determined by the state-of-the-art next-generation sequencing of 16S rRNA. Crucial to intestinal health is the establishment of a well-balanced gut microbiota community, which frequently happens at the time of first feeding. At this stage, the intestinal immune system is not mature and allows colonisation of the gut by symbiotic bacterial species. We will use zebrafish to study these early life events, with the key goal to test whether manipulation of gut microbiota improves the oral tolerance to sustainable aquaculture diets with high inclusion of plant proteins and vegetable oils. Thus, the microbiota swap between zebrafish larvae fed with fish- or plant-based diets may open up new avenues for investigating pathways to improved health and immune function in farmed fish. Finally, both salmon on different dietary regimes (and associated changes in gut microbiota) and zebrafish with manipulated gut microbiota will be exposed to a bacterial pathogen to determine whether the capacity of the fish to fight the infection depends on prior intestinal condition and microbiota community. The important part of the project will be development of molecular diagnostic tools for fish gut microbiota, enabling rapid screening for beneficial and detrimental sets of bacteria in fish guts. The main outputs of the project include:1) Identification of key microbiota species associated with gut health and intestinal dysfunction in farmed fish (salmon) and a model species (zebrafish).2) Evaluation of the capacity of gut microbiota to modify gut function and applicability of gut microbiota transfer to improve oral tolerance of farmed fish to plant-based diets.3) Development of assays for detection of microbiota species, which can be used to create diagnostic tests for gut health.

全球鲑鱼产量约为 150 万吨，英国目前约为 17 万吨，每年为英国鲑鱼经济带来约 10 亿英镑的收入。英国水产养殖的大部分位于苏格兰，占苏格兰总产量的 40% 以上。三文鱼养殖是一个不断增长的食品工业部门，苏格兰的目标是到 2020 年将其产量增加 50%。这种增长的一个主要瓶颈是提供不会对三文鱼产生不利影响的高质量饲料。鲑鱼是鱼食性动物，传统的鲑鱼饲料依赖于野生来源的鱼蛋白和鱼油，这已无法满足全球水产养殖业的需求。为了克服这一短缺，人们正在使用植物蛋白和植物油来替代野生来源的鱼蛋白和鱼油。水产养殖饲料中的鱼类存在与这种替代相关的许多主要问题和限制，包括营养消化率降低、肠道炎症、肠道微生物失衡和对病原体的抵抗力受损。用鱼粉和植物性饮食喂养的斑马鱼模型，以了解这些不同的饮食如何影响早期肠道发育、免疫功能和肠道微生物群之间的关系，斑马鱼提供了一个独特的模型来研究这种复杂的关系，因为它们是半透明的，并且具有建立了许多先进的实验技术，包括无菌幼虫的产生、荧光标记细菌定植的幼虫的实时成像以及荧光蛋白标记炎症细胞的鱼类的产生，这些技术目前都不适用于鲑鱼或其他动物。通过进行鲑鱼喂养试验，我们将确定植物性饮食如何影响肠道健康（肠道形态和基因表达谱的变化）以及它们如何改变肠道微生物群的丰度和多样性，从而确定肠道微生物群的多样性。通过最先进的下一代 16S rRNA 测序，建立均衡的肠道微生物群落对肠道健康至关重要，这种情况经常发生在首次喂养时，肠道免疫。系统是我们将使用斑马鱼来研究这些早期生命事件，其关键目标是测试肠道微生物群的操纵是否可以提高对含有大量植物蛋白和的可持续水产养殖饮食的口服耐受性。因此，以鱼类或植物性饮食喂养的斑马鱼幼虫之间的微生物群交换可能为研究改善养殖鱼类的健康和免疫功能开辟新途径。不同的饮食习惯（以及肠道微生物群的相关变化）和肠道微生物群被控制的斑马鱼将暴露于细菌病原体，以确定鱼抵抗感染的能力是否取决于先前的肠道状况和微生物群落项目。鱼类肠道微生物群的分子诊断工具，能够快速筛查鱼类肠道中有益和有害的细菌组。该项目的主要成果包括：1）鉴定与肠道健康和肠道功能障碍相关的关键微生物群物种。养殖鱼类（鲑鱼）和模式物种（斑马鱼）。2) 评估肠道微生物群改变肠道功能的能力以及肠道微生物群转移的适用性，以提高养殖鱼类对植物性饮食的口服耐受性。3) 开发用于检测微生物群种类的测定，可用于创建肠道健康的诊断测试。

项目成果

Differential responses of the gut transcriptome to plant protein diets in farmed Atlantic salmon.

养殖大西洋鲑鱼肠道转录组对植物蛋白饮食的差异反应。

• DOI: http://dx.10.1186/s12864-016-2473-0
• 发表时间: 2016
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Król E

Atlantic salmon (Salmo salar) parr as a model to predict the optimum inclusion of air classified faba bean protein concentrate in feeds for seawater salmon

大西洋鲑鱼（Salmo salar）帕尔作为模型来预测海水鲑鱼饲料中空气分级蚕豆浓缩蛋白的最佳添加量

• DOI: 10.1016/j.aquaculture.2015.03.024
• 发表时间: 2015-07-01
• 期刊: Aquaculture
• 影响因子: 4.5
• 作者: C. Santis;K. Ruohonen;D. Tocher;S. Martin;E. Król;C. Secombes;J. Bell;A. El;V. Crampton
• 通讯作者: V. Crampton

Environmental and physiological factors shape the gut microbiota of Atlantic salmon parr (Salmo salar L.).

环境和生理因素影响大西洋鲑鱼 (Salmo salar L.) 的肠道微生物群。

• DOI: http://dx.10.1016/j.aquaculture.2016.07.017
• 发表时间: 2017
• 期刊: Aquaculture (Amsterdam, Netherlands)
• 作者: Dehler CE

Transcriptomic responses in the fish intestine.

鱼肠中的转录组反应。

• DOI: 10.1016/j.dci.2016.03.014
• 发表时间: 2016-11-01
• 期刊: Developmental and comparative immunology
• 影响因子: 2.9
• 作者: S. Martin;C. Dehler;E. Król
• 通讯作者: E. Król

Seawater transfer alters the intestinal microbiota profiles of Atlantic salmon (Salmo salar L.).

海水转移改变了大西洋鲑鱼（Salmo salar L.）的肠道微生物群特征。

• DOI: http://dx.10.1038/s41598-017-13249-8
• 发表时间: 2017
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Dehler CE