Professor Simon Carding, Institute of Food Research, Norwich
Tuesday 15th December, 1.00 p.m., Keynes Lecture Theatre 6
It is becoming clear that crosstalk between the intestinal microbiota and gut epithelial cells plays an important role in gut health. Considerable efforts are now being made to determine the precise nature of the dialog between gut bacteria and the human host. Much of the previous work in this area has focused on the roles of diffusible, small-molecule hormones and nutrients. We have uncovered a new vehicle pathway utilised by prevalent commensal Gram-negative gut bacteria, including Bacteroides thetaiotaomicron (Bt), in which biologically active proteins and metabolites are packaged into outer membrane vesicles (OMVs) for release into the lumen and delivery to barrier epithelial cells. Our initial characterisation of Bt-OMVs identified a homolog of a mammalian cell-signaling inositol hexakisphosphate (InsP6) phosphatase, MINPP that in the gut lumen can contribute to digestion of dietary phytate and upon internalization by epithelial cells promotes intracellular Ca2+ signaling. Subsequent analyses of OMV cargo has identified proteins involved in cell adhesion, antibiotic resistance and metabolism that have the potential to impact on enteric microbial ecology and interactions with the host. We have also developed the capability of engineering Bt to produce OMVs containing heterologous proteins of significant health benefit to the host. Our characterization of vesicularized bacterial products challenges established orthodoxies concerning our understanding of the mechanisms by which symbiotic bacteria in the mammalian GI-tract interact with their host and offer several new directions for understanding how the microbiome serves human physiology and health.