Terence Crofts, PhD

Pre-term and very low birth weight infants are routinely given antibiotic therapy in the first days of life. This exposure to antibiotics very early in life has been associated with lower phylogenetic diversity of the gut microbiota and increased risk of necrotizing enterocolitis, sepsis and death. I am interested in investigating the contribution of the complex and dynamic natural gut microbiota towards preventing these outcomes. As yet there is no model system to study the impact of early life antibiotic therapy on infant human gut microbiota, nor is there a model system to test treatment efficacy following disruption of this ecosystem. I propose the development of a murine model in which a human maternal gut microbiota is established in a gnotobiotic female mouse for natural transference to infant mice, following which the effect of exposure to antibiotics on the infant mouse humanized gut microbiota will be monitored. We will sequence community 16S rRNA genes, track the spread of antibiotic resistance and monitor changes to the host phenotype. Establishing this model will allow us to test interventions targeted at returning the microbiota to a healthy state, providing potential insights into therapies that may improve the outcomes of at risk infants.