The Game for Three: Salmonella-Host-Microbiota Interaction Models

Colonization of the gastrointestinal (GI) tract by enteric pathogens occurs in a context strongly determined by host-specific gut microbiota, which can significantly affect the outcome of infection. The complex gameplay between the trillions of microbes that inhabit the GI tract, the host, and the infecting pathogen defines a specific triangle of interaction; therefore, a complete model of infection should consider all of these elements. Many different infection models have been developed to explain the complexity of these interactions. This review sheds light on current knowledge, along with the strengths and limitations of in vitro and in vivo models utilized in the study of Salmonella-host-microbiome interactions. These models range from the simplest experiment simulating environmental conditions using dedicated growth media through in vitro interaction with cell lines and 3-D organoid structure, and sophisticated "gut on a chip" systems, ending in various animal models. Finally, the challenges facing this field of research and the important future directions are outlined.