Grant: Project Grant

The bacteria that colonize the human intestine are a critical determinant of health and susceptibility to disease such as inflammatory bowel disease (IBD) and neurological disorders. The epithelial lining of the gut is the primary point of contact with these bacteria and hence knowing how the epithelium acts as a barrier to exclude the entry of bacteria into the body and how the epithelial cells respond when bacteria penetrate them or cross the epithelial barrier is central to health and well-being. Mitochondria are the cells' power-station, generating the energy needed for the cell to function and are generally described as a discrete organelle - both positions are overly simplified: mitochondria form a complex, dynamic network that remodels by the controlled processes of fission and fusion, and they produce signaling molecules (mainly reactive oxygen species) that direct many cellular events. We showed that epithelial cells with deranged mitochondrial activity have reduced barrier function and actually internalize bacteria: both events have implications for health and disease management. Loss of epithelial barrier function could precipitate local inflammation and potentially sepsis, and bacteria inside the epithelial cells are likely a threat requiring mobilization of immune activity that could result in tissue damage. There is surprisingly little information on how mitochondrial function regulates epithelial-bacteria interaction and how bacterial pathogens or pro-inflammatory signals regulate mitochondrial form and function, particularly fusion and fission: the latter promoting cell death which would contribute to loss of epithelial barrier function. We have developed a novel study with leading edge technologies to precisely examine how mitochondria mould the epithelial-bacterial relationship in the gut. With this knowledge we will be better positioned to advance approaches to maintain digestive health and treat (or cure) gut problems such as IBD.