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

Haq, Mohammad Raies Ul; Kapila, Rajeev; Sharma, Rohit; Saliganti, Vamshi; Kapila, Suman

doi:10.1007/s00394-013-0606-7

Cited by 90 publications

(72 citation statements)

References 35 publications

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“…The proteins, gluten and casein, are hydrolyzed in the GI tract into hundreds to thousands of peptides, some of which have been shown to have opioid-like properties and are referred to as exorphins (Boutrou et al, 2013; Dohan, 1988a; Dohan, 1979, 1980, 1988b; Prandi et al, 2014; Reichelt, 1991, 1994; Reichelt et al, 1985; Reichelt et al, 1981; Reichelt et al, 1995; Reichelt et al, 2012). The immunomodulatory potential of these exorphins is not well-understood, with observations that among the repertoire of digested peptides, some have pro-inflammatory and others have anti-inflammatory effects (Aihara et al, 2014; Barnett et al, 2014; Haq et al, 2014; Kaminski et al, 2007). The mechanisms by which peptides derived from wheat gluten and bovine milk casein or the associated immune response might be pathogenic in schizophrenia are not known.…”

Section: Introductionmentioning

confidence: 99%

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

Severance¹,

Gressitt²,

Alaedini³

et al. 2015

Brain, Behavior, and Immunity

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Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R2=0.34–0.55, p≤0.0001; controls R2=0.05–0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p≤0.001–0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature.

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Section: Introductionmentioning

confidence: 99%

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

Severance¹,

Gressitt²,

Alaedini³

et al. 2015

Brain, Behavior, and Immunity

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“…A ação da β-caseína A1 e do BCM-7 resultante de sua hidrólise na irritação intestinal tem sido estudada em ratos e humanos, embora poucos estudos tenham sido conduzidos até o momento. Em um estudo feito com ratos, no qual foram administradas β-caseínas isoladas de leites contendo apenas β-caseína A1 (leite A1), β-caseína A2 (leite A2) e uma mistura de βcaseína A1 e A2 (leite A1), por doses de 85mg/dia, sendo solução salina utilizada como controle, foi observado aumento em indicadores de inflamação intestinal associados com ambos os tipos de leite A1(proveniente de gado geneticamente caracterizado como A1/A1 e A1/A2) se comparados com A2 ou controle [31]. O consumo de leite A1 aumentou significativamente a atividade de mieloperoxidase (marcador de inflamação) no tecido intestinal (p < 0,01) e concentrações de IL-4, IgE, IgG, IgG1 e IgG2a e infiltração de leucócitos no intestino.…”

Section: β-Caseína A1 β-Casomorfina-7 E Irritação Intestinalunclassified

“…No exame histológico, o consumo de leite A1 aumentou significativamente o número de leucócitos nas vilosidades intestinais se comparado com controle e com o A2, que não apresentou diferença entre eles. Este estudo apontou, portanto, possível agravo da resposta inflamatória por consumo de β-caseína A1 [31] .…”

Section: β-Caseína A1 β-Casomorfina-7 E Irritação Intestinalunclassified

Leites A1 e A2: revisão sobre seus potenciais efeitos no trato digestório

Barbosa

Souza

Tavares

et al. 2019

Segur. Aliment. Nutr.

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O leite de vaca é o mais consumido no Brasil e na maioria dos outros países. Neste produto a β-caseína representa aproximadamente 30% do total de proteínas, podendo esta estar presente como duas diferentes variantes de acordo com a genética do animal: β-caseína A1 e A2. O peptídeo opioide β-casomorfina-7 (BCM-7) pode ser liberado durante a digestão da β-caseína A1, no entanto sua liberação durante a digestão da β-caseína A2 é pequena à inexistente. Este artigo tem como objetivo discutir o potencial efeito do consumo das variantes genéticas A1 e A2 da β-caseína sobre o trato digestório. Existe um corpo de evidências apontando para a presença BCM-7 como responsável pela síndrome de intolerância ao leite não relacionada com a lactose, com efeitos sobre motilidade gastrintestinal e ação pró-inflamatória. Dada a complexidade das reações bioquímicas e fisiológica que se observam no ambiente intestinal é razoável esperar que os sintomas, quando presentes, irão variar dependendo da sensibilidade interpessoal. A avaliação do consumo de leite A2 como alternativa dietética entre indivíduos que reportam desconforto gastrointestinal por consumo de leite de vaca (não associado à lactose) é recomendável tendo em vista a importância que os lácteos representam no aporte de nutrientes fundamentais à saúde humana.

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Section: Introductionmentioning

confidence: 99%

“…Therefore, EFSA did not recommend any formal risk linked to such food-derived peptides. In all cases, nowadays "A2 milk" is produced in different countries, and further studies have been carried out on the disadvantages of A1 milk, mainly pointing out its potential negative effects on human digestive function [11][12][13][14]. Different methods are available for the separation and quantification of bovine milk protein variants by reversed phase high-performance liquid chromatography (RP-HPLC) [15] or high resolution HPLC-mass spectrometry (HPLC-MS) [16].…”

Section: Introductionmentioning

confidence: 99%

Detecting β-Casein Variation in Bovine Milk

et al. 2016

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Abstract:In bovine species, β-casein (β-CN) is characterized by genetic polymorphism. The two most common protein variants are β-CN A 2 (the original one) and A 1 , differing from A 2 for one amino acid substitution (Pro 67 to His 67 ). Several bioactive peptides affecting milk nutritional properties can originate from β-CN. Among them, β-casomorphin-7 (BCM7) ranging from amino acid 60 to 66 can be released more easily from β-CN variants carrying His 67 (A 1 type) instead of Pro 67 (A 2 type). Nowadays, "A2 milk" is produced in different countries claiming its potential benefits in human health. The aim of this study was to further develop and apply an isoelectric focusing electrophoresis (IEF) method to bulk and individual milk samples in order to improve its use for β-CN studies. We succeeded in identifying A2 milk samples correctly and quantifying the percentage of A 2 , A 1 , and B variants in bulk samples not derived from A2 milk as well as in individual milk samples. The method allows us to quantify the relative proportion of β-CN variants in whole milk without eliminating whey protein by acid or enzymatic precipitation of caseins. The aim of this study was also to study the different behavior of β-CN and β-lactoglobulin (β-LG) in the presence of trichloroacetic acid (TCA). The higher sensitivity of β-CN to TCA allows quantifying β-CN variants after TCA fixation because β-LG is not visible. Monitoring β-CN variation in cattle breeds is important in order to maintain a certain balance between Pro 67 and His 67 in dairy products. Overall, the debate between A1 and A2 milk needs further investigation.

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

Cited by 90 publications

References 35 publications

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

Leites A1 e A2: revisão sobre seus potenciais efeitos no trato digestório

Detecting β-Casein Variation in Bovine Milk

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