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Our laboratory investigates how the immune system has adapted to the diverse microbial agents we encounter in our lifetime. We address this question by focusing on the gastrointestinal tract where a single layer epithelium separates our body from pathogens and microbial colonizers belonging to the microbiota. Through taking a comparative infection biology approach, our research has identified mechanisms by which cellular processes such as autophagy promote a balanced immune response that protects against life-threatening infections while avoiding chronic illnesses like inflammatory bowel disease. We will discuss our ongoing efforts in characterizing how genetic susceptibility alters the mucosal immune system when encountering infectious triggers. Through these research studies, we hope to gain further insight into how microbial diversity in the intestinal ecosystem shapes host physiology and pave the way for therapies that restore balanced host-microbe relationships.