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

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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.