Enteric pathogens have evolved to manipulate the interface between the host and commensal microbial communities, making these pathogenic organisms superb research tools to interrogate the function of the gut microbiota during inflammatory flares. Here, we provide an overview of conceptual insights gained from experimental infection with enteric pathogens, such as Salmonella enterica serovar Typhimurium. Metabolic pathways at the host–microbe intersection will be a particular area of focus. A better understanding of the cellular and molecular mechanisms that control host–microbe interactions during episodes of inflammation may aid in the rational design of microbiota-targeting therapies.