The importance of environment in immune response is identified and the increase in prevalence of allergic, autoimmune and chronic inflammatory diseases reviewed. In particular, altered opportunity to acquire evolutionarily anticipated commensal microbiota is associated through the “hygiene hypothesis” with defective developmental and response signals to the innate and adaptive immune systems. Evidence of the detrimental effects of such environments is reviewed as is evidence for remediation using controlled exposure to bacteria
or their active components such as LPS or peptidoglycan ligands for TLR and NOD-like receptors. Occurrence of major environmentally associated changes in porcine immune response phenotype are described. Recent studies of pigs indicate important detrimental effects of indoor housing and use of antibiotics on the profile of intestinal commensals and potential pathogens. Using allergy as a model of a modern disease predisposed by high hygiene conditions, it has been shown that unidentified environmental effects can drastically alter prevalent immune response phenotype.  Simulating healthy environments by treating neonatal pigs with killed E. coli or with living L. lactis significantly prevents allergic signs, an effect that is correlated with reduced type-2 bias in immune response and also induces clinical tolerance even in the face of classical evidence of allergic sensitization. Opportunities exist for functional studies of these positive immunoregulatory approaches. The high frequency of clinical tolerance to developing allergic signs even in the face of classical sensitization indicates possible function in this pig model of regulatory effectors such as Treg cells.