Immune Responses Against Commensal Bacteria

The bacteria that inhabit the gut, also known as the commensal microbiota, are of central importance to the mucosal immune response. The Hand Lab focuses on how environmental changes may strain the host/microbiota relationship. Our previous work has shown that enteric infection can significantly alter interactions between the microbiota and the host immune system. We are interested in how various perturbations, such as infection, changes in diet, etc., may affect intestinal immune responses and health long-term.

Ours and other laboratories have shown that gastrointestinal inflammation leads to the outgrowth of the Enterobacteriaceae family of bacteria. We have developed tools to study these organisms from the perspective of the immune system. However, we are also very interested in making modifications in the commensals themselves to determine the critical factors that allow for the outgrowth of these organisms and their affect on the host immune response.

It is quite clear that the changes that we have made during our evolution to a Western diet have profound consequences for the organisms inhabiting our intestines. We would like to look at how specific shifts in our diet can lead to changes to the microbiota and in particular its interaction with the host immune system.

Finally, it is now established that the immune system measures “keystone metabolites” to assess the fitness of the microbiota. We are interested in how enteric pathogens may take advantage of these metabolites to subvert the immune system to their own requirements.