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Comparative evaluation of cow β-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut



Recently, apprehension has been raised regarding “A1/A2 hypothesis” suggesting relationship between consumption of A1 “like” variants of cow β-casein and various physiological disorders. The information available is based on either the human epidemiological data of milk consumption or in vitro trials on cell lines with β-casomorphin peptides. The direct scientific evidence establishing the link between consumption of A1/A2 “like” milk and health is scanty. Thus, under present investigation, in vivo trials in mice were undertaken to study the effect of feeding three genetic variants (A1A1, A1A2 and A2A2) of cow β-casein milk on gastrointestinal immune system as it is the first and foremost site of immunological interactions.


Animals were divided into four groups for feeding with basal diet (control) and β-casein isolated from milk of genotyped (A1A1, A1A2 and A2A2) dairy animals, respectively. Gut immune response was analyzed by spectrophotometric assessment of MPO activity, quantitative sandwich ELISA of inflammatory cytokines (MCP-1 and IL-4), antibodies (total IgE, IgG, sIgA, IgG1 and IgG2a) and qRT-PCR of mRNA expression for toll-like receptors (TLR-2 and TLR-4). Histological enumeration of goblet cells, total leukocytes and IgA+ cells was also carried out.


It was observed that consumption of A1 “like” variants (A1A1 and A1A2) significantly increased (p < 0.01) the levels of MPO, MCP-1, IL-4, total IgE, IgG, IgG1, IgG2a and leukocyte infiltration in intestine. TLR-2 and TLR-4 mRNA expression was also up-regulated (p < 0.01) on administration of A1 “like” variants. However, no changes in sIgA, IgA+ and goblet cell numbers were recorded on consumption of any of the β-casein variants.


It is reasonable to conclude that consumption of A1 “like” variants of β-casein induced inflammatory response in gut by activating Th2 pathway as compared to A2A2 variants. The present study thus supports the purported deleterious impacts of consumption of A1 “like” variants of β-casein and suggests possible aggravation of inflammatory response for etiology of various health disorders.

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The authors are grateful to the Director of National Dairy Research Institute (ICAR), Karnal, for providing funding and laboratory facilities to carry out this piece of work.

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The authors declare that they have no conflict of interest.

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Correspondence to Rajeev Kapila.

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Haq, M.R.U., Kapila, R., Sharma, R. et al. Comparative evaluation of cow β-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut. Eur J Nutr 53, 1039–1049 (2014).

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  • β-Casein variants
  • β-Casomorphins
  • Inflammation
  • Humoral response
  • Cytokines