Intestinal pathogens causing either clinical or sub-clinical infections increase pig morbidity and (or) mortality, resulting in economic losses and wider socio-economic impacts on pig production. An optimally functioning gastrointestinal tract (GIT) is fundamental to combatting intestinal pathogen colonisation at all the stages of life. This requires successful development and maintenance of key gut functions: digestive function; the gastro-intestinal cell line barrier; gut-associated lymphoid tissue (GALT); and gut-associated microbiota. This chapter first discusses research on genes associated with pathogen resistance and porcine immune response. It then reviews risk factors associated with gut mucosa impairment as well as dietary strategies to control risk factors and improve gut functionality in preventing intestinal pathogen colonisation.