Principles of community development within the gut microbiome (360G-Wellcome-201341_Z_16_Z)

The human gut harbours a complex and dynamic community of microbes that are considered crucial for good health. However, we understand little about the acquisition and development (succession) of this critical community. I will build an empirical and theoretical framework, designed to interrogate the drivers of microbiome development. Specifically, I will construct mechanistic models of microbiome communities, alongside developing tools with which these can be parameterised from longitudinal datasets. These models will then be embedded within a theoretical framework inspired by traditional ecology in order to study microbiome succession. Comprehensive in silico analyses will be combined with a multidisciplinary investigation of a known neonatal microbiome community in order to identify key drivers of succession, which will then be tested empirically using forward genetics and community manipulations in vivo. This will give insight into both the specific features of the neonatal microbiome, and the broader drivers of microbiome succession, as well as enabling iterative improvement of the modelling framework. The acquisition and development of ‘healthy’ microbiome communities is critical for host wellbeing, with disturbances here correlating with a range of diseases. Determining what governs community development will therefore be vital if we wish to better understand and manipulate our microbiome.