Rationally designed probiotic approaches to combat antibiotic-associated diarrhoea
File(s)
Author(s)
Panwar, Rekha Bharat
Type
Thesis
Abstract
The intestinal microbiota is a diverse population of microbes colonising environmentally exposed body surfaces. The microbiota shares a mutualist relationship with the host, where it plays an important role in protection against pathogen colonisation and infection, also known as colonisation resistance. The ecological balance within the gastrointestinal microbiota can be perturbed by several factors but is most dramatically affected by antibiotic treatment. Imbalance in the commensals can lead to various intestinal problems, including antibiotic-associated diarrhoea (AAD) and infection. Evidence from animal and human studies suggests that anaerobic gut commensals confer protection against pathogens. However, the key members contributing to this colonisation resistance are still largely undefined, making therapeutic and commercial use of the microbiota hard to achieve. Thus, the aim of this project is to identify members of the microbiota providing pathogen resistance. We have cultured and identified a commensal panel which has been screened for antagonism against a range of major antimicrobial resistant pathogens. After screening 65 commensals, we have identified antagonistic gut commensals against all the pathogens in our panel. Of the inhibitory commensals identified, three Bacteroidetes commensals inhibit Staphylococcus aureus via modification of host bile acids. Using a range of biochemical and microbiological approaches, we have shown that Bacteroidetes metabolise conjugated bile acids, and these modified bile acids kill S. aureus...
Version
Open Access
Date Issued
2023-12-19
Date Awarded
2024-09-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Clarke, Thomas
Sponsor
Medical Research Council (Great Britain)
Publisher Department
Department of Infectious Disease
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)