The human gut is colonized by a diverse microbial community collectively referred to as the gut microbiota. A healthy gut microbiota provides protection against intestinal colonisation by pathogens, however disruption of the gut microbiota can weaken colonisation resistance (e.g. following exposure to antibiotics), increasing the host’s susceptibility to enteric infections. The aim of our research is to develop novel microbiome therapeutics to restore microbiota-mediated colonisation resistance and decolonise pathogens from the intestine. In our previous work we identified a bacterial metabolite (valerate) and a microbial enzyme (bile salt hydrolase) that significantly inhibits Clostridioides difficile germination and vegetative growth following faecal microbiota transplantation (FMT).
Current work in our laboratory is focusing on investigating novel methods to re-establish microbiota-mediated colonisation resistance in patients colonised with multidrug-resistant organisms (MDROs). Antimicrobial resistance is a serious threat to human health, resulting in treatment failures, infection relapses, longer hospitalisations, and poor clinical outcomes. The intestine is the primary colonisation site for MDROs and serves as a reservoir for MDROs that are responsible for invasive infections (e.g. sepsis and recurrent urinary tract infections). Studies have demonstrated intestinal decolonisation of carbapenem-resistant Enterobacteriaceae and extended spectrum β-lactamase-producing Enterobacteriaceae following FMT. However, the mechanism of FMT is unknown, and there are several drawbacks to administering FMT to MDRO colonised patients. The goal of our research is to determine the mechanism(s) by which FMT decolonises MDROs from the intestine, with the aim to develop a new method for MDRO intestinal decolonisation.
Our lab uses a variety of complementary approaches to study gut colonisation resistance, including artificial gut models (aka “chemostat” or “Robogut” models), batch culture experiments, patient faecal samples, and mouse intervention experiments. Samples are analysed using both culture-dependent and culture-independent techniques, including a variety of “omic” techniques (e.g. 16S rRNA gene sequencing, 1H-NMR spectroscopy, and a variety of mass spectrometry techniques).
Summary of different mechanisms of gut microbiota-mediated colonisation resistance that can be used to develop new microbiome therapeutics.
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