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

小隐孢子虫会导致幼畜急性腹泻，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。当寄生虫在牛粪便中传播并污染供水时，可发生人畜共患疾病在人群中的传播。这会导致水样腹泻，在免疫系统较弱的人群中尤其严重，对他们来说，唯一获得许可的治疗方法无效。因此，如果我们能够制定更好的策略来控制牛隐孢子虫，我们不仅可以减轻农场隐孢子虫病的经济和福利负担，而且可以防止人畜共患传播和人类疾病。新生牛犊对隐孢子虫特别敏感，我们认为这可能是因为生活在肠道中的有益菌群还没有完全成熟。如果这是正确的，那么通过提供益生菌，早期建立一个稳定的、有益的细菌群落可以保护新生牛犊免受严重隐孢子虫病的侵害。该项目将使用牛的肠道干细胞来生成肠道的3D组织培养模型（称为肠样，或“迷你肠道”）。学生将测试添加特定细菌（如商业兽医益生菌，从牛小肠中分离的群落）或其产品（如短链脂肪酸）如何影响肠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。

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.