For approximately 10,000 years, cattle have been our major source of meat and dairy. However, cattle are also a major reservoir for dangerous foodborne pathogens that belong to the Shiga toxin-producing Escherichia coli (STEC) group. Even though STEC infections in humans are rare, they are often lethal, as treatment options are limited. In cattle, STEC infections are typically asymptomatic and STEC is able to survive and persist in the cattle GIT by escaping the immune defenses of the host. Interactions with members of the native gut microbiota can favor or inhibit its persistence in cattle, but research in this direction is still in its infancy. Diet, temperature and season but also industrialized animal husbandry practices have a profound effect on STEC prevalence and the native gut microbiota composition. Thus, exploring the native cattle gut microbiota in depth, its interactions with STEC and the factors that affect them could offer viable solutions against STEC carriage in cattle.