Foodborne enteric diseases cause millions of illness and thousands of deaths annually in the United States. Major enteric bacterial pathogens include Salmonella, enterohemorrhagic Escherichia coli O157:H7 (EHEC), Campylobacter, Listeria, Shigella, Vibrio, and Yersinia which account for more than 90% cases of culture-confirmed infections. Among these causative agents, Salmonella enterica is responsible for the highest rate of hospitalization and EHEC has the lowest infectious dose. Their pathogenesis involves numerous virulent factors whereas their colonization and invasion on host gut intestine mainly depend on the type III secretion system. The prevention of foodborne enteric diseases is of great concern to public health professionals, farmers, and food producers. Due to the increased public health concern about antibiotic-resistance dissemination, alternative strategies such as pro-commensal approach by applying probiotics, prebiotics, and combination of both (synbiotics) are of interests for prevention and therapy of foodborne enteric diseases. In this study, we both in vitro and in vivo evaluated the preventive capabilities of Lactobacillus against enteric pathogenic bacterial colonization and infection. Functional food cocoa and peanut containing prebiotic-like ingredients selectively promoted the growth of beneficial bacteria and stimulated the production of bio-active metabolites especially conjugated linoleic acids in Lactobacillus. We also detected the synergistic effects of Lactobacillus and cocoa/peanut on competitive exclusion of S. Typhimurium and EHEC, alteration on physicochemical properties, disruption of host-pathogen interactions, and down-regulation on virulence gene expressions. Furthermore, with homologous recombination, we overexpressed myosin cross-reactive antigen gene encoding linoleate isomerase in L. casei and improved the efficiency in their linoleic acids production as well as the gut intestinal adherence and colonization. By applying genetically engineered LC-CLA, S. Typhimurium and EHEC were much effectively controlled and restricted from all aspects in vitro mentioned before. Additionally, the in vivo pre-administration of LC-CLA reduced S. Typhimurium gut intestinal colonization/infection in a significant level and induced anti-inflammatory effects, which benefitted the overall mice gut health. Our findings established a baseline upon which self-promoting probiotic independent from prebiotic in prevention or treatment against enteric diseases can be explored.