The Effect of Raw and Processed Bovine Milk Consumption on Immune Responses in Allergy and Health

Abstract

A large body of epidemiological evidence shows that children who consume raw bovine milk in early life have reduced incidence of allergies and asthma in later life; while consumption of heat-treated, or processed milk, does not confer protection. Potential safety risks from consuming unpasteurised bovine milk make controlled intervention studies in human infants difficult, as such, direct causation is lacking. Thus, there is a need to investigate if raw bovine milk can prevent allergy development, using non-human models. It is not known whether raw bovine milk confers any immunomodulatory outcomes in vivo that are not conferred by a heat-treated bovine milk. Understanding the contribution of raw milk to immune responses could vindicate the exploration of raw bovine milk for immunogenic factors that are diminished by processing and lead to greater understanding of the effects of raw bovine milk on the immune system. This thesis, therefore, utilised two separate, but connected, areas of investigation to test raw bovine milk’s immunomodulatory effects in both an allergic and non-allergic context. Mouse models were used to test the potential of raw bovine milk feeding to mitigate allergy development in comparison to commercially pasteurised and homogenised (processed) bovine milk. Raw bovine milk’s ability to alleviate hypersensitivity responses in two food allergy models in mice was tested. One model utilised intraperitoneal injection as a route of sensitisation and intragastric challenge. The second model used intragastric sensitisation and challenge. The results from food allergy models show that feeding mice raw bovine milk could lessen hypersensitivity responses in the form of antigen-specific antibodies in the plasma of mice and could reduce antigen specific cytokine responses by splenocytes in vitro compared to mice fed processed bovine milk. To elucidate whether raw bovine milk had discernible effects on a naïve, healthy immune system in mice, the effects of raw bovine milk feeding were compared to processed bovine milk feeding, assessing changes in T cell responses in vivo. Raw bovine milk feeding induced activation of both conventional CD4+ T cell and Tregs compared to processed milk and water feeding, in mice, and further, led to highly divergent cytokine profiles in the spleen. It was found that both local and systemic immune responses could be successfully induced by raw bovine milk feeding and these effects were either not present or were diminished, in processed milk fed mice. In conclusion, it was found that raw bovine milk can modulate the immune system in a model organism in both health and allergy. These results lend understanding of raw bovine milks potential effects in vivo. It was shown in this thesis that commercially available bovine milk, both in an allergic and non-allergic context had reduced immunomodulation in comparison to raw milk. The results from this thesis validate that raw bovine milk as a whole food has immunogenic properties able to elicit immune responses and justifies seeking to understand more clearly the factors responsible for this effect.