Investigating the effect of farm milk consumption on childhood asthma and allergies in the context of farming, early life nutrition and innate immunity

Background In the past 20 years, investigations in affluent countries repeatedly found that an exposure to farming environments was associated with lowered risks for atopic disease in childhood. Subsequently, consumption of cow’s milk from farms that was not commercially processed was consistently identified as one specific protective farm related factor. Microorganisms, fatty acids and proteins in milk were speculated to possibly underlie these inverse associations of farm milk with atopic outcomes. The pathways mediating this potential protection remain unclear. Recent research findings indicated an involvement of the innate immune system. Objectives To elucidate the previously observed inverse associations of farm milk consumption with childhood asthma and allergic disease by identifying underlying milk components, by putting these results in the context of similar associations of farm related and dietary exposures and by assessing the role of the innate immune system. Methods The cross-sectional GABRIEL study was conducted in rural areas of Germany, Switzerland, Austria and Poland. The initial study population comprised 103’219 6-12 year old children. Atopic health outcomes and farming and lifestyle exposures were assessed by comprehensive questionnaires. Cow’s milk was collected as it was consumed at the participants’ homes from about 800 children. The prospective birth cohort study PASTURE was conducted in rural areas of Germany, Austria, Switzerland and Finland. Initially, 1’133 pregnant women were recruited in the third trimester. Environmental exposures and self reports about atopic disease were assessed by extensive questionnaires during pregnancy and yearly up to age 6. A detailed food frequency diary during year 1 provided information on introduction of complementary foods. Blood samples were used to measure gene expression of innate immunity receptors at birth and age 1. Results A traditional type of farming namely with cows and cultivation was protective for childhood asthma, hay fever and atopy. The inverse association of general farm exposure with asthma could be explained by early life consumption of farm milk, contact with cows and contact with straw. The association with atopy, hay fever and atopic dermatitis could not be fully explained by these factors. Reported consumption of unboiled farm milk was significantly associated with reduced risk for asthma, atopic sensitization, hay fever and atopic dermatitis. Whey proteins (bovine serum albumin, α-lactalbumin, β-lactoglobulin) were identified as milk constituents possibly explaining the epidemiologically observed protective farm milk association with asthma whereas reduced risk for atopic sensitization could not be associated with any investigated milk constituent. Microorganisms and fat content of milk showed no associations with allergic health outcomes. Increasing diversity of introduced complementary food items was inversely associated with the risk to develop atopic dermatitis after age 1, independently of other farming exposures. An inverse association was also found with the introduction of yogurt during the first year of life. Maternal farming during pregnancy was associated with a significant up-regulation of Toll-like receptors (TLR) 7 and 8 gene expressions. Child’s farm milk consumption during first year of life was associated with up-regulation of TLR4, 5 and 6 gene expression. Conclusions and outlook The variations between associations of specific farming and dietary exposures in early life with specific atopic diseases suggest that different pathways may be involved in the protection against the development of these outcomes. Several factors explained the decreased risk for asthma in children living on farms but specific factors explaining decreased risks for atopy, hay fever and atopic dermatitis are yet to be identified. Our findings add to the evidence that early life exposures may have an effect on the development of the innate immune system. We could further demonstrate that relevant exposures differed between in utero and child’s direct exposure during first year of life. Results generated with cross-sectional data need to be confirmed in prospective studies to establish temporal relationships and future studies need to employ more advanced methods to assess microbial diversity in environmental exposures. An important research question for further investigations will be whether and how the innate immune system mediates the inverse associations of farm related and dietary exposure with the development of atopic disease in early life. Raw milk consumption has the potential to be used as preventive measure for the development of atopic disease in early life but pathogens pose a health risk and make an implementation unlikely. A native milk product that is safe and can still exert “protective effects” on atopic diseases could be facilitated by modern non-thermal pasteurization techniques.