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Simple Summary: Prescribed examination of enterohemorrhagic Escherichia coli (EHEC) O157:H7 microbiota–host interactions in the gastrointestinal tract of cattle is technically difficult due in part to the high cost of conducting research with cattle, the genetic heterogeneity among animals, the logistic challenges of obtaining prescribed samples, and the variability in the structure of the enteric microbiota among individuals. Thus, our overarching goal was to develop a prescribed enteric colonization model utilizing germ-free mice inoculated with individual bovine EHEC O157:H7 strains representing the primary genetic lineages of the pathogen. Moreover, we utilized the colonization model with or without stress induced via the administration of corticosterone to examine the ability of commensal E. coli strains to outcompete EHEC O157:H7 in vivo. A bovine strain of EHEC O157:H7 that incited reduced pathologic changes was identified, and the administration of 18 commensal E. coli strains isolated from cattle effectively reduced densities of the pathogen, and ameliorated histopathologic changes and markers of inflammation. Although stress has been identified as a factor affecting colonization success, we observed that physiological stress did not benefit enteric colonization by EHEC O157:H7. Despite its limitations, the defined microbiota murine enteric colonization model developed may prove useful for identifying mechanisms and mitigation strategies for subsequent validation in cattle. Cattle are a primary reservoir of enterohemorrhagic Escherichia coli (EHEC) O157:H7. Currently, there are no effective methods of eliminating this important zoonotic pathogen from cattle, and colonization resistance in relation to EHEC O157:H7 in cattle is poorly understood. We developed a gnotobiotic EHEC O157:H7 murine model to examine aspects of the cattle pathogen–microbiota interaction, and to investigate competitive suppression of EHEC O157:H7 by 18 phylogenetically distinct commensal E. coli strains of bovine origin. As stress has been suggested to influence enteric colonization by EHEC O157:H7 in cattle, corticosterone administration (±) to incite a physiological stress response was included as an experimental variable. Colonization of the intestinal tract (IT) of mice by the bovine EHEC O157:H7 strain, FRIK-2001, mimicked characteristics of bovine IT colonization. In this regard, FRIK-2001 successfully colonized the IT and temporally incited minimal impacts on the host relative to other EHEC O157:H7 strains, including on the renal metabolome. The presence of the commensal E. coli strains decreased EHEC O157:H7 densities in the cecum, proximal colon, and distal colon. Moreover, histopathologic changes and inflammation markers were reduced in the distal colon of mice inoculated with commensal E. coli strains (both propagated separately and communally). Although stress induction affected the behavior of mice, it did not influence EHEC O157:H7 densities or disease. These findings support the use of a gnotobiotic murine model of enteric bovine EHEC O157:H7 colonization to better understand pathogen–host–microbiota interactions toward the development of effective on-farm mitigations for EHEC O157:H7 in cattle, including the identification of bacteria capable of competitively colonizing the IT. [ABSTRACT FROM AUTHOR]