Development of novel microbiome-based strategies for biocontrol of C. difficile.

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Clostridioides difficile is the most common cause of hospital-acquired life-threatening infections and the incidence has escalated in recent years due to the high number of patients on broad-spectrum antibiotic therapy. While antibiotic treatment is effective, ~28% of the patients suffer from relapse. C. difficile is also becoming resistant to many of the antibiotics, and alternatives to antibiotic treatment are urgently required. One such strategy, is the use of faecal therapy where gut microbes from a healthy donor is given to patients to reconstitute a healthy gut microbiome that can resist proliferation of C. difficile. Recent studies of faecal therapy suggest a greater than 90% success rate, particularly in those patients suffering from chronic relapse. However, faecal therapy is aesthetically unappealing to patients and the healthcare workers, and there are also potential risks of transferring unknown pathogens from the donor to the patient. The aim of this project is to develop a cocktail of bacteriophages or bacterial metabolites that can be formulated as a defined treatment to give a safer, more appealing alternative to faecal transplantation. Such cocktails will be designed to modulate the gut microbiome which result in protection against C. difficile infections. The effective designed formulations will then be optimised with the objective of developing human trials in the future.