**5. Conclusion**

This chapter shows that we get clearer evidence that the food‐ and water‐borne pathogens ETEC and EHEC are able to adapt to each of the successive environments of the human GI tract by reading many cues provided by both the host and the gut microbiota. Exposure to different environmental cues may impact pathogen survival but also alter the expression of virulence genes. Nevertheless, the data obtained until now show many gaps and inconsisten‐ cies. In particular, most of the current studies have been carried out using oversimplified *in vitro* approaches, and what is still missing is the integration of signals delivered in a sequential but not in an isolated fashion. Relevant alternatives to better understand how ETEC and EHEC respond to these various cues in a temporal‐spatial fashion may imply relevant animal mod‐ els (e.g., human microbiota‐associated animals) [94] or digestion models closely mimicking the human digestive tract, such as the TIM or the SHIME (Simulator of the Human Intestinal Microbial Ecosystem) [95]. In particular, TIM and SHIME would be of high interest to (i) assess how the modalities of ingestion (e.g., infectious dose, growth phase, and food vehicle) and age conditions (adult, infant, and elderly) may influence pathogen survival and virulence in the human GI tract, (ii) investigate how ETEC and EHEC interact with luminal and mucosal gut microbiota under physiological fluid shear stresses and microaerobic conditions, and (iii) study host‐microbiota‐pathogen interactions by using intestinal cells in culture coupled with TIM or SHIME models, like in the HMI (host microbe interactions) module [96]. For an in‐ depth understanding of pathogen behavior in the human GI tract, these models should be used in combination with new technologies such as ‐omics or quantitative imaging technologies.
