Rational microbial-based interventions against bacterial enteric diseases in young livestock.

Neonatal calves and piglets are susceptible to a range of enteric bacterial infections including neonatal scour caused by Salmonella spp. and Escherichia coli. Such infections can be life threatening. The economic impact of these diseases should also be taken in consideration as well as related public health concerns due to the potential foodborne zoonotic nature of these enteric pathogens. Previously antimicrobials have often been used to reduce the risk of these infections, though the emergence of antimicrobial resistant variants have led to such use being increasingly regulated and reduced. The use of microbial-based interventions such as probiotics is seen as a key alternative to antibacterial drugs given a good safety record and ease of administration by farmers. However, these have mostly been developed empirically, which limits their applicability. A rational approach for the development and design of microbial interventions offers the opportunity to modulate the microbiome effectively.

Aims and objectives

The aims and objectives of this project are:

• Identifying and selecting existing or novel bacterial taxa or consortia through the comparative study of the microbiota in health and disease.
• Assessing their therapeutic potential against the most common bacterial enteric infections of young livestock through an in vitro infection ultrastructural study of the microorganism-microorganism and microorganism-host interactions. The study will be carried out using 2D and 3D cell in vitro and ex-vivo culture systems and microfluidic techniques and will allow us to evaluate the potential beneficial effects and mechanisms of the selected bacteria on both the host and the pathogens.

Methodology

1. Use DNA sequencing of 16S amplicons to detect key Amplified Sequence Variants (ASVs) to determine taxa present in the healthy pig and calf gut but depleted in animals with enteritis as potential novel probiotics associated with good ‘gut health’.
2. Develop and refine 2D and 3D porcine and bovine intestinal cell cultures and precision cut slice ex vivo techniques using microfluidic systems.
3. Select potential novel and currently available probiotics to test both singly and as consortia for phenotype in cell culture model.
4. Develop and refine a cell-culture infection model of both porcine and bovine epithelial cells and intestinal tissues as a platform to assess the use of selected probiotic bacteria and their supernatants on reducing pathogen invasion, modulating the immune/inflammatory response, maintaining tight-junction/barrier integrity in order to define potential candidates for future in vivo testing, and the mechanisms by which they act. This platform can support a range of analyses from transcriptional approaches to detailed EM imaging. The student will be exposed and gain experience on different disciplines/techniques including microbiology, cell culture, pathology, immunology, imaging and microscopy. The microbiome sequencing will develop skills in genomics and basic bioinformatic analysis of the microbiome.

Apply for this project

This project will be based in Bristol Veterinary School.

Please contact bvs-pgrstudent-admin@bristol.ac.uk for further details on how to apply.

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