Biosecurity standards and farming practices have profoundly changed the way domestic animals interact with the environment and themselves. Farm intensification processes resemble the lifestyle changes that humans underwent post industrialization, which have been linked to the occurrence of immune-mediated and metabolic disorders. Modern rearing practices reduce maternal and offspring interactions, promote changes in diet, restrict animals indoors, and rely on the use of antibiotics and vaccines to maintain animal health. These practices may hinder the proper colonization of the gastrointestinal tract with commensal organisms that co-evolved with livestock species. The gut microbiota aids nutrient digestion, stimulates immune and intestinal development and maturation, and promotes the competitive exclusion of pathogens. Microbial colonization in early life is critical for host metabolic and immune programming, and disruptions of gut microbial community stability can lead to development of metabolic and immune disorders seen at later stages of life. Identifying how farming practices influence microbial composition and the potential effects on host physiology, metabolism, and disease resistance is necessary to guide intervention strategies to promote beneficial microbial–host interactions, and improve animal health and performance.