Human microbiota encompass the populations of microorganisms that live on and in human organ systems. Importantly, a large proportion of the microbiota lies in the digestive tract. Gut microbes facilitate beneficial, and necessary, metabolic and protective processes within their hosts. Imbalances in gut microbial load or composition may lead to inflammation and changes in intestinal physiology, ultimately impacting whole organism health. Currently, we understand that age-related changes in gut microbiota are a primary source of immune activation. However, the cause-effect relationships between microbiota dynamics, immune activity, and changes in intestinal health are not yet fully understood. The fruit fly, Drosophila melanogaster, has enabled us to show how chronic immune activation in young flies drives early-onset mortality as well as increased loss of barrier function. Changes in digestive transit and microbial populations are also characteristics of flies that experience immune activation throughout life. Thus, there are clear physiological changes that occur not just with age, but also as a product of immune responses in the fly. A better understanding of microbial and immune pathway dynamics may allow for development of interventions to delay age-related decline.