Dataset Information

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

ABSTRACT: 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?CD25^-FoxP3? 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.

SUBMITTER: Chia JSJ

PROVIDER: S-EPMC6163334 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chia Joanne S J JSJ McRae Jennifer L JL Enjapoori Ashwantha Kumar AK Lefèvre Christophe M CM Kukuljan Sonja S Dwyer Karen M KM

Nutrients 20180912 9

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 f ...[more]

PMID: 30213104

Similar Datasets

Project description:BackgroundCows' milk generally contains two types of β-casein, A1 and A2 types. Digestion of A1 type can yield the peptide β-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 β-casein with those of milk containing only A2 β-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance.MethodsForty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both β-casein types or milk containing only A2 β-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events.ResultsCompared with milk containing only A2 β-casein, the consumption of milk containing both β-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and β-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the SCIT. Consumption of milk containing both β-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 β-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects.ConclusionsConsumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein.Trial registrationClinicalTrials.gov/NCT02406469.

Project description:The objective of this study was to determine whether adding phytoncide oil (PO) and soybean oil (SBO) to the dairy cow diet could increase milk conjugated linoleic acid (CLA) and depress methane (CH4) emissions in Holstein dairy cows. Rumen fermentation was conducted at four levels of SBO (0, 1, 2, and 4%, on DM basis) and two levels of PO (0 and 0.1%, on DM basis) with in vitro experiment. To evaluate blood parameters, fecal microbe population, milk yield and fatty acid compositions, and CH4 production, in vivo experiment was conducted using 38 Holstein dairy cows divided into two groups of control (fed TMR) and treatment (fed TMR with 0.1% PO and 2% SBO as DM basis). In the in vitro study (Experiment 1), PO or SBO did not affect rumen pH. However, SBO tended to decrease ruminal ammonia-N (p = 0.099). Additionally, PO or SBO significantly decreased total gas production (p = 0.041 and p = 0.034, respectively). Both PO and SBO significantly decreased CH4 production (p < 0.05). In addition, PO significantly increased both CLA isomers (c9, t11 and t10, c12 CLA) (p < 0.001). Collectively, 0.1% PO and 2% SBO were selected resulting in most effectively improved CLA and decreased CH4 production. In the in vivo study (Experiment 2), 0.1% PO with 2% SBO (PSO) did not affect complete blood count. However, it decreased blood urea nitrogen and magnesium levels in blood (p = 0.021 and p = 0.01, respectively). PSO treatment decreased pathogenic microbes (p < 0.05). It increased milk yield (p = 0.017) but decreased percentage of milk fat (p = 0.013) and MUN level (p < 0.01). In addition, PSO treatment increased both the concentration of CLA and PUFA in milk fat (p < 0.01). Finally, it decreased CH4 emissions from dairy cows. These results provide compelling evidence that a diet supplemented with PSO can simultaneously increase CLA concentration and decrease CH4 production with no influence on the amount of milk fat (kg/day) in Holstein dairy cows.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets