When colonized, poultry shed enteric pathogens in the feces that may readily and persistently cause threats to public health via the poultry-meat and the hen eggs. Outbreaks are reported regularly involving 'Salmonella ' Enteritidis, 'Salmonella' Typhimurium, 'Camplylobacter jejuni', and 'Escherichia coli' O157:H7. Therefore, controlling these pathogens on the farm may reduce the spread of human food-borne diseases and minimize economic losses. A primary goal of this work was to find a novel, practical, economical and safe method of intervening in the colonization of poultry by human pathogens during production. An animal model of gastroenteritis was employed where laying hens were fed a diet supplemented with either non-immunized egg yolk powder that does not contain specific antibodies against food borne pathogens, delipidated egg yolk proteins, egg white or skim milk powder to determine the effects on either preventing colonization by pathogens or eliminating bacteria established in the gut. The four food borne pathogens included in the experiments were 'S'. Enteritidis, ' S'. Typhimurium, 'C. jejuni', and 'E. coli' O157:H7 A comparative study was also conducted between non-immunized and immunized egg yolk powder containing specific anti-Salmonella Enteritidis antibodies against 'S'. Enteritidis colonization in laying hens. Results revealed an important and novel discovery where egg yolk powder without containing specific antibodies was by far the most effective in controlling pathogen colonization in laying hens. The immunoglobulin component of egg yolk was not the active fraction nor responsible for the anti-infectious activities observed. This animal study anticipated the presence of novel anti-adhesive component(s) in the hen-egg yolk. 'In vitro' experiments were conducted using confluent Caco-2 cell monolayers and identified the novel protective yolk fraction against the food borne pathogens as the granule component, mainly the high-density lipoproteins (HDL). The protective activity conveyed by HDL was confirmed as anti-adhesive and not anti-microbial. Non-immunized egg yolk powder also reduced the pathogen colonization in the internal organs, notably the ovary, oviduct, and intestine reducing the likelihood of egg contamination. The supplements did not negatively affect the intestinal microflora nor the hens' body weight or the mean weight and number of eggs laid per hen. Therefore, supplementing the diet of hens with non-immunized egg yolk powder seems to be an effective and useful tool in controlling bacterial food-borne illness. The present study unveils a novel discovery of egg yolk granules and high-density lipoproteins as possessing anti-adhesive activity against pathogenic ' Salmonella' spp. and 'E. coli'.