Comparing to three other enteric pathogens in OligoMM mice reveals pathogen-specific host and microbiota responses.

, non-typhoidal spp., and enteropathogenic/enterohemorrhagic (EPEC/EHEC) are leading causes of food-borne illness worldwide. has been used to model EPEC and EHEC infection in mice. The gut microbiome is well-known to affect gut colonization and host responses to many food-borne pathogens. Recent progress has established gnotobiotic mice as valuable models to study how microbiota affect the enteric infections by . Typhimurium, and . However, for , we are still lacking a suitable gnotobiotic mouse model. Moreover, the limited comparability of data across laboratories is often negatively affected by variations between different research facilities or murine microbiotas. In this study, we applied the standardized gnotobiotic OligoMM microbiota mouse model and compared the infections in the same facility. We provide evidence of robust colonization and significant pathological changes in OligoMM mice following infection with these pathogens. Moreover, we offer insights into pathogen-specific host responses and metabolite signatures, highlighting the advantages of a standardized mouse model for direct comparisons of factors influencing the pathogenesis of major food-borne pathogens. Notably, we reveal for the first time that stably colonizes OligoMM mice, triggering inflammation. Additionally, our comparative approach successfully identifies pathogen-specific responses, including the detection of genes uniquely associated with infection in humans. These findings underscore the potential of the OligoMM model as a versatile tool for advancing our understanding of food-borne pathogen interactions.