The gastrointestinal tract in both mammals and insects is associated with microbes (collectively the microbiota), which are controlled by the intestinal immune system. These microbes regulate pathogens that can infect gut epithelial cells, and there is increasing evidence for a reciprocal relationship between beneficial and pathogenic bacteria in the gut and the intestinal immune system. Deciphering these complex interactions between the microbiota and intestinal immune system in mammals requires surrogate model systems, such as larvae of the greater wax moth Galleria mellonella. The exposure of G. mellonella microbiota to antibiotics induces immunity and stress-related genes in the intestine. The model can also provide insight into the virulence mechanisms of pathogens such as Listeria monocytogenes in the human gut and brain. We also discuss the current uses of G. mellonella as a model to develop therapeutic strategies against listeriosis.