Characterisation of the hospital-acquired diarrhoeal gut microbiota and metabolome in response to infectious and non-infectious factors

Non-infectious causes of hospital acquired-diarrhoea alter the gut microbial community, increase susceptibility to gut infections and compromise health outcomes. By studying the microbiota and metabolome associated with hospital-acquired diarrhoea, this thesis shows that antibiotic treatment causes the greatest disturbance. The study also shows that Clostridioides difficile, a significant hospital pathogen, colonises and causes disease in a range of antibiotic disrupted environments. Importantly, C. difficile infection can be differentiated from non-C. difficile infection through by-products of C. difficile amino acid fermentation. Furthermore, changes in the composition and abundance of these by-products as the gut environment becomes increasingly challenging, demonstrate how C. difficile gains a foothold the gut through securing energy from a range of amino acids. The findings are clinically significant and provide further insights into how C. difficile exploits a range of gastrointestinal environments to proliferate and cause disease.