Exposure to early life adversity (ELA) is a significant risk factor in later life susceptibility to inflammatory disorders, including allergy, asthma and chronic pain disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Mast cells (MCs) are innate immune cells known to play central roles in inflammatory disorders and have been linked in the pathophysiology of stress-induced diseases. The mechanistic link between ELA and later life MC disease is poorly defined. The aim of this study was to investigate whether ELA impacts long-term MC activity and MC mediator content and additionally, determine whether ELA increased adult MC disease susceptibility. The objective of this dissertation was to determine the long-term impact of early life adversity on mast cell phenotype and function. To answer these questions we utilized a validated early life adversity model of maternal separation and early weaning in mice to further subject to various mast cell disease models. Additionally, we collected bone marrow derived mast cells from these animals to further analyze their phenotype.The results presented here demonstrate that ELA induces long- lasting changes in MC hyperactivity, mediator content and responses in addition to vulnerability to later life stress and clinical GI dysfunction, with females more at increased risk. Future research will be aimed at elucidating the mechanisms through which ELA programs MC development and function and its role in exacerbating later life GI and allergic disease models.
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