Using stem cell-derived "mini-guts" to determine the role of the microbiota in resistance to Cryptosporidium infection in cattle

使用干细胞衍生的“迷你肠道”确定微生物群在抵抗牛隐孢子虫感染中的作用

• 批准号: 2269996
• 金额: --
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2269996
• 关键词: Using; stem; cell; derived; mini

Cryptosporidium parvum causes acute diarrhoea in young calves, which can be fatal. Infection is common, and carries significant economic and welfare costs. Zoonotic transmission to human populations can occur when the parasite is shed in cattle faeces, and contaminate water supplies. This causes watery diarrhoea, which is particularly severe in people with weakened immune systems, for whom the only licenced treatment is ineffective. Therefore, if we could develop better strategies to control Cryptosporidum in cattle, we would not only reduce the economic and welfare burden of cryptosporidiosis on farms, but also prevent zoontotic transmission and human disease. Neonatal calves are particularly susceptible to Cryptosporidium, and we think that this may be because the community of beneficial bacteria living in the intestine has not fully matured. If this is correct, then early establishment of a stable, beneficial bacterial community through provision of probiotics could protect neonatal calves against severe cryptosporidiosis. This project will use intestinal stem cells from cattle to generate 3D tissue culture models of the intestine (termed enteroids, or "mini-guts"). The student will test how the addition of specific bacteria (e.g. commercial veterinary probiotics, communities isolated from the small intestines of cattle) or their products (e.g. short chain fatty acids) influence the health or disease status of intestinal epithelial cells, and their ability to resist infection with Cryptosporidium.

微小隐孢子虫会引起幼犊的急性腹泻，这可能是致命的。感染很常见，并带来巨大的经济和福利成本。当寄生虫从牛的粪便中排出，并污染供水时，可能会发生人畜共患传播到人群中。这会导致水样腹泻，在免疫系统较弱的人中尤为严重，对他们来说，唯一获得许可的治疗是无效的。因此，如果我们能够制定更好的策略来控制牛的隐孢子虫病，我们不仅可以减轻隐孢子虫病在农场的经济和福利负担，还可以防止人畜共患病和人类疾病的传播。新生牛犊特别容易感染隐孢子虫，我们认为这可能是因为生活在肠道中的有益细菌群落尚未完全成熟。如果这是正确的，那么通过提供益生菌尽早建立一个稳定的、有益的细菌群落可以保护新生牛犊免受严重的隐孢子虫病的侵袭。该项目将使用来自牛的肠道干细胞来生成肠道的3D组织培养模型(称为肠样细胞，或“迷你肠道”)。学生将测试添加特定细菌(例如商业兽用益生菌、从牛的小肠中分离的群落)或其产品(例如短链脂肪酸)如何影响肠道上皮细胞的健康或疾病状态，以及它们抵抗隐孢子虫感染的能力。