Colonisation Resistance

One of the fundamental roles the microbiota plays is resisting infection by invading pathogens. However, it is currently unclear how different members of the early life microbiota mediate these beneficial effects, or how pathogens overcome these responses to cause disease.

The gut microbiota represents a complex community of trillions of different microbes, who are in constant ‘competition’ with each other. We are therefore interested in understanding how different beneficial microbiota members (like Bifidobacterium) may outcompete pathogenic microbes via their ability to more efficiently digest dietary components (see Diet-Microbiota interactions), obtain factors that are normally scarce in the gut (e.g. iron), and produce novel anti-microbial compounds. We also have a focus on pinpointing putative virulence factors of important neonatal-associated pathogens (e.g. Clostridium perfringens), and how these clinically relevant microbes may spread in at-risk populations. We use multi-disciplinary approaches to probe these questions including development of new bioinformatic pipelines which we can apply to sequencing or transcriptional data, in vitro assays, molecular microbiology approaches, proteomics and metabolomics. We hope these projects will allow us to identify key strains able to provide critical colonisation resistance against pathogens including E. coli, Salmonella and Clostridium.

Development of novel anti-infection strategies is particularly important considering the rise in antimicrobial resistance (AMR). Infants often receive many courses of antibiotics, which alongside disturbing the gut microbiota may also contribute to the ‘resistome’ i.e. carriage of antimicrobial resistance and virulence genes within the early life microbial community. To tackle this important issue, we are developing new ‘diagnostic’ approaches, that can profile the gut microbiota and identify potential pathogens and their AMR profile. We are also using different molecular and computational approaches to explore the impact of antibiotics on the early life gut microbiota (using BAMBI and PEARL samples), including understanding how AMR genes may move around within the microbial community, including transfer of resistant genes to pathogenic species.