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Open AccessArticle

Dietary Cows’ Milk Protein A1 Beta-Casein Increases the Incidence of T1D in NOD Mice

Immunology Research Centre, St. Vincent’s Hospital, Fitzroy, Victoria 3065, Australia
Metabolic Research Unit, School of Medicine, Deakin University, Geelong, Victoria 3216, Australia
Division of Bioinformatics, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3000, Australia
Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Victoria 3010, Australia
Peter MacCallum Cancer Centre, Melbourne, Victoria 3010, Australia
Freedom Foods Group Ltd., Sydney, New South Wales 2229, Australia
Department of Nephrology, St. Vincent’s Health, Melbourne, Victoria 3065, Australia
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2018, 10(9), 1291;
Received: 3 August 2018 / Revised: 6 September 2018 / Accepted: 8 September 2018 / Published: 12 September 2018
(This article belongs to the Special Issue The Impact of Beverages on Ingestive Behavior)
The contribution of cows’ milk containing beta-casein protein A1 variant to the development of type 1 diabetes (T1D) has been controversial for decades. Despite epidemiological data demonstrating a relationship between A1 beta-casein consumption and T1D incidence, direct evidence is limited. We demonstrate that early life exposure to A1 beta-casein through the diet can modify progression to diabetes in non-obese diabetic (NOD) mice, with the effect apparent in later generations. Adult NOD mice from the F0 generation and all subsequent generations (F1 to F4) were fed either A1 or A2 beta-casein supplemented diets. Diabetes incidence in F0–F2 generations was similar in both cohorts of mice. However, diabetes incidence doubled in the F3 generation NOD mice fed an A1 beta-casein supplemented diet. In F4 NOD mice, subclinical insulitis and altered glucose handling was evident as early as 10 weeks of age in A1 fed mice only. A significant decrease in the proportion of non-conventional regulatory T cell subset defined as CD4+CD25FoxP3+ was evident in the F4 generation of A1 fed mice. This feeding intervention study demonstrates that dietary A1 beta-casein may affect glucose homeostasis and T1D progression, although this effect takes generations to manifest. View Full-Text
Keywords: type 1 diabetes; beta-casein; cows’ milk; epigenetics; NOD mice type 1 diabetes; beta-casein; cows’ milk; epigenetics; NOD mice
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Chia, J.S.J.; McRae, J.L.; Enjapoori, A.K.; Lefèvre, C.M.; Kukuljan, S.; Dwyer, K.M. Dietary Cows’ Milk Protein A1 Beta-Casein Increases the Incidence of T1D in NOD Mice. Nutrients 2018, 10, 1291.

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