The role of the gut microbiota in regulating mucosal macrophage homeostasis and inflammation

Our immune system must fight harmful pathogens, but remain silent against harmless substances such as the trillions of bacteria found in the gut that are beneficial for health. If our immune system attacks these microbiota, inflammatory bowel diseases (IBD), such as Crohn’s disease, can occur. These are painful, debilitating conditions that affect millions of people worldwide, and although the causes are poorly understood, there is mounting evidence that previous antibiotic use may be important, especially if used in early life. However, it is unknown why use of antibiotics increases IBD risk. My preliminary results indicate that antibiotic use causes immune cells called macrophages to become overactive in the gut, resulting in long-lived inflammation.

I will examine how antibiotics cause changes in gut macrophages that may lead to IBD. As it is now known that antibiotic use in childhood also predisposes to asthma, I will explore if antibiotics also make lung macrophages more active and if this contributes to inflammatory disease in the lung.

This study will determine how gut and lung macrophages control the immune system in health and how antibiotic use might disrupt this process, allowing inflammation to develop, with the potential for identifying new drug targets.