Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Dietary polyphenols reduced the allergenicity ofβ-lactoglobulin via non-covalent interactions:a study on the structure-allergenicity relationship

Studies showed that complexation of polyphenols with milk allergens reduced their immunogenic potential.However,the relationship between structures of polyphenols and their hypoallergenic effects on milk allergens in association with physiological and conformational changes of the complexes remain unclear.In this study,polyphenols from eight botanical sources were extracted to prepare non-covalent complexes withβ-lactoglobulin(β-LG),a major allergen in milk.The dominant phenolic compounds bound toβ-LG with a diminished allergenicity were identified to investigate their respective role on the structural and allergenic properties ofβ-LG.Extracts from Vaccinium fruits and black soybeans were found to have great inhibitory effects on the IgE-and IgG-binding abilities ofβ-LG.Among the fourteen structure-related phenolic compounds,flavonoids and tannins with larger MWs and multi-hydroxyl substituents,notably rutin,EGCG,and ellagitannins were more potent to elicit changes on the conformational structures ofβ-LG to decrease the allergenicity of complexedβ-LG.Correlation analysis further demonstrated that a destabilized secondary structure and protein depolymerization caused by polyphenol-binding were closely related to the allergenicity property of formed complexes.This study provides insights into the understanding of structure-allergenicity relationship ofβ-LG-polyphenol interactions and would benefit the development of polyphenol-fortified matrices with hypoallergenic potential.

Cow’s milk-induced gastrointestinal disorders:From infancy to adulthood

Milk is related to many gastrointestinal disorders from the cradle to the grave due to the many milk ingredients that can trigger gastrointestinal discomfort and disorders.Cow’s milk protein allergy(CMPA)is the most common food allergy,especially in infancy and childhood,which may persist into adulthood.There are three main types of CMPA;immunoglobulin E(IgE)-mediated CMPA,non-IgEmediated CMPA,and mixed type.CMPA appears before the first birthday in almost all cases.Symptoms may start even during the neonatal period and can be severe enough to simulate neonatal sepsis.CMPA(often non-IgE mediated)can present with symptoms of gastroesophageal reflux,eosinophilic esophagitis,hemorrhagic gastritis,food protein-induced protein-losing enteropathy,and food protein-induced enterocolitis syndrome.Most CMPAs are benign and outgrown during childhood.CMPA is not as common in adults as in children,but when present,it is usually severe with a protracted course.Lactose intolerance is a prevalent condition characterized by the development of many symptoms related to the consumption of foods containing lactose.Lactose intolerance has four typical types:Developmental,congenital,primary,and secondary.Lactose intolerance and CMPA may be the underlying pathophysiologic mechanisms for many functional gastrointestinal disorders in children and adults.They are also common in inflammatory bowel diseases.Milk consumption may have preventive or promoter effects on cancer development.Milk may also become a source of microbial infection in humans,causing a wide array of diseases,and may help increase the prevalence of antimicrobial resistance.This editorial summarizes the common milk-related disorders and their symptoms from childhood to adulthood.

Assessment of a Precaution Index for Environmental Evaluation: An Example of Application to the Cow’s Milk Production

The paper presents a Precaution Index (P) developed to create an instrument to assess the potential risk related to the presence of pollution sources next to milk production farms. The methodology starts from the inventory and geo-referencing of all pollution sources in an area, with the help of the multi-criteria decision analysis. Results are represented in a map of P, which highlights which areas are most at risk and need monitoring, and which pollutants may be involved. This may help in the early identification of emerging hazards to food safety. P was calculated for the milk production in an Italian region. Results show that 97% of the area is in a condition of minimum precaution that would be needed in controlling the safety of dairy products.

Anticlastogenic Effect of Redistilled Cow's Urine Distillate in Human Peripheral Lymphocytes Challenged With Manganese Dioxide and Hexavalent Chromium

Objective To study the anticlastogenic effect of redistilled cow＇s urine distillate （RCUD） in human peripheral lymphocytes （HLC） challenged with manganese dioxide and hexavalent chromium. Methods The anticlastogenic activity of redistilled cow＇s urine distillate was studied in human polymorphonuclear leukocytes （HPNLs） and human peripheral lymphocytes in vitro challenged with manganese dioxide and hexavalent chromium as established genotoxicants and clastogens which could cause induction of DNA strand break, chromosomal aberration and micronucleus. Three different levels of RCUD： 1 μL/mL, 50 μL/mL and 100 μL/mL, were used in the study. Results Manganese dioxide and hexavalent chromium caused statistically significant DNA strand break, chromosomal aberration and micronucleus formation, which could be protected by redisfilled cow＇s urine distillate. Conclusion The redistilled cow＇s urine distillate posseses strong anfigenotoxic and antielastogenic properties against HPNLs and HLC treated with Cr^＋6 and MnO2. This property is mainly due to the antioxidants present in RCUD.

Effects of Cow’s Milk on Reproduction in ICR Male Mice

Objective To study the effects of Cow＇s milk on the reproduction in male mice. Methods Twenty-four male mice were divided randomly into two groups： milk group （M） and control group （C）. Each mouse was given 10 mL milk per day from 4 to 16 weeks in the group M. At the age of 17 weeks, all the mice were sacrificed. Results Serum testosterone was decreased in the group M （P=0.037）. No significant difference was found in weight of testes, seminal vesicle or adrenal gland of mice between the groups C and M. However, the weight of seminal vesicle decreased when expressed in g/100 g body weight in the group M. Epididymal sperm concentration, motility, morphology, and sperm head number were not affected by milk. Conclusion Cow＇s milk has adverse effects on the reproductive system in ICR male mice. Further studies are needed to clarify the specific effects of milk on reproductive health.

Molecularly defined adult-type hypolactasia in school-aged children with a previous history of cow's milk allergy

AIM： To assess the role of lactase non-persistence/per- sistence in school-aged children and their milk-related symptoms. METHODS： The genotypes for the C/T-13910 variant associated with lactase non-persistence/ persistence were determined using PCR-minisequencing in a group of 172 children with a mean age of 8.6 years （SE = 0.02, 93 boys） participating in a follow-up study for cow＇s milk allergy. The parents were asked to assess their children＇s milk consumption and abdominal symptoms. RESULTS： The presence of allergy to cow＇s milk was not associated with the C/C-13910 genotype related with a decline of lactase enzyme activity during childhood （lactase non-persistence）. The frequency of the C/C-13910 genotype （16%） was similar to published figures for the prevalence of adult-type hypolactasia in Finland. The majority of the children （90%） in this series consumed milk but 26% of their families suspected that their children had milk-related symptoms. Forty-eight percent of the children with the C/C-13910 genotype did not drink milk at all or consumed a low lactose containing diet prior to the genotyping （P〈 0.004 when compared to the other genotypes）. CONCLUSION： Analysis of the C/T-13910 polymorphism is an easy and reliable method for excluding adult-type hypolactasia in children with milk-related symptoms. Genotyping for this variant can be used to advise diets for children with a previous history of cow＇s milk allergy.

Evaluation of the Physicochemical Parameters of Cow’s Fresh Milk in Shkodra

Milk is universally recognized as complete food, which contains essential components for human nutrition. Physicochemical analysis constitutes an important device that monitors its quality. The purpose of this study was to determine the physicochemical characteristics of fresh cow milk in samples taken in the region of Shkodra and Lezha and compare it to European quality standards. Results of the analyses were statistically processed by the Minitab 17 statistical program. Results showed that there is no significant difference (P > 0.05) in fat, protein, lactose and density value, while there is significant difference (P < 0.05) in pH, ash% without fat, freezing point and water value. The results show a stability of physicochemical parameters of milk, with variation according to the region where samples were gathered.

Preparation of Polyclonal Antisera of Dairy Cow S100A12 Protein

[Objective] This study aimed to prepare dairy cow anti-S100A12 antisem and develop a highly effective and sensitive immunological detection reagent for further investigation of the functions of dairy cow S100A12. [Method] Purified S100A12 protein was respectively emulsified with Freund＇s complete adjuvant and Freund＇s incomplete adjuvant as the antigen for immunizing New Zealand white rabbits to prepare the polyclonal antisera. The titer was detected using agar double diffusion assay and indirect enzyme-linked immunoserbent assay （ELISA） and the specificity was determined with Western Blot. [ Result ] The titer of anti- S100A12 antisera was 1： 8 as determined by agar double diffusion assay and over 1：409 600 by ELISA. Western Blot result showed that the polyclonal antisera could be specifically combined with S100A12 protein. [ Conclusion] The results indicated that anti-S100A12 polyclonal antibody with high fiter and high specificity was successfully obtained, which provided a novel tool for further investigation of the functions of S100A12 gene.

Cow milkα_(s1)-casein induces allergic responses in a mouse model of atopy

α_(s1)-Casein is a potential allergen to induce hypersensitivity in cow milk.We had identifiedα_(s1)-casein and its epitopes in previous studies.The present study aimed to evaluate the allergic mechanism ofα_(s1)-casein in a BALB/c mouse model.The levels of specific IgE,mast cell proteinase,histamine and cytokines in sensitized mice were determined,and the clinical and pathological observation were evaluated.Results showed that the levels of specific IgE,mast cell proteinase,histamine,IL-4,IL-5,IL-10 increased significantly with a dose-dependent trend.The local alveolar septum collapsed or thickened,and lymphatic foci were produced in the spleen and thymus,and the inflammatory cells infiltrated in small intestinal mucosa mesenchyme.In conclusion,the levels of specific IgE,mast cell proteinase,histamine,IL-4,IL-5,IL-10 and some inflammatory factors could possibly serve as allergic biomarkers ofα_(s1)-casein,however,additional studies on signal transduction and gene expression are necessary in future.

Bisphenol A in Fluid and Powdered Milk Samples and Associated Child Dietary Exposures

Bisphenol A (BPA) is a synthetic chemical found in a wide range of consumer products and consumables that humans are exposed to. The aim of this study was to determine BPA contamination levels in 51 milk samples sold in the Rio de Janeiro Metropolitan Region, Brazil. Bisphenol A was detected (≥limit of detection, LOD) in five of the analyzed samples (9.8%) and quantified (≥limit of quantification, LOQ) in two (3.8%). The estimated daily intake (EDI) for children aged up to 12 months ranged from 24.95 to 97.72 ng/kg body weight/day, lower than the established European Union tolerable daily intake value. Recent evidence, however, suggests that even low doses of endocrine disruptors such as BPA may pose potential health risks, even more so when exposure occurs at such an early life stage.

奶牛子宫内膜炎化脓隐秘杆菌16SrRNA基因的鉴定与分析

对内蒙古呼和浩特地区奶牛子宫内膜炎化脓隐秘杆菌进行了分离鉴定。经生化实验鉴定的化脓隐秘杆菌利用PCR技术扩增其16S rRNA基因,得到1.5 kb目的片段;将目的片段与T载体连接,测定目的片段的基因序列,与GenBank公布的化脓隐秘杆菌16S rRNA基因序列进行比较分析,其同源率为93%～100%。本试验共分离到化脓隐秘杆菌32株。

奶牛微生物培养物BLS的研究

用鉴别培养基从土壤、新疆传统奶酪和马奶酒中分离出地衣芽孢杆菌、米酒乳杆菌和酿酒酵母。经鉴定和安全试验 ,上述三株菌混合后的联合培养物 ,接种生料发酵制成微生态制剂BLS ,饲喂泌乳牛。试验组平均每日奶产量显著高于对照组。

徐州地区0~3岁婴幼儿牛奶蛋白过敏的临床特征及影响因素分析

目的了解徐州地区0~3岁婴幼儿牛奶蛋白过敏(CMPA)的临床特征及影响因素分析,为临床诊断和治疗提供参考。方法选取2019年10月至2022年10月徐州地区0~3岁婴幼儿为研究对象,采用问卷调查的形式收集所有对象的临床特征,评估其营养水平并开展实验室检查。根据皮肤点刺试验和牛奶回避/激发试验结果确诊CMPA患儿。评估病情严重程度并分析CMPA患儿的临床特征及影响因素。根据皮肤点刺试验和IgE检查结果将患儿分为免疫球蛋白E(IgE)介导型和非IgE介导型,比较不同类型患儿临床症状和实验室检查结果。结果共纳入4983例0~3岁婴幼儿进行研究。4983例婴幼儿中共检出CMPA患儿124例,发病率为2.49%。不同年龄婴幼儿,CMPA发病率比较,差异有统计学意义(χ^(2)=10.065,P=0.002),且1~2岁和>2岁婴幼儿的CMPA发病率均高于<1岁的婴幼儿(χ^(2)=5.258,P=0.022;χ^(2)=8.055,P=0.005)。早产儿及父母有过敏史的婴幼儿CMPA发病率显著高于非早产儿及父母无过敏史者,差异均有统计学意义(χ^(2)=6.881,P=0.009;χ^(2)=9.753,P=0.002)。124例CMPA患儿中IgE介导型26例(20.97%),非IgE介导型98例(79.03%)。IgE介导型发生呕吐/胃食管反流的发生率显著低于非IgE介导型(χ^(2)=11.668,P=50.001),而发生湿疹/风团/红斑、流涕/咳嗽/喘息、口周红肿和累及2个及以上系统的发生率显著高于非IgE介导型(χ^(2)=32.975,P<0.001;χ^(2)=10.000,P=0.002;χ^(2)=17.293,P<0.001;χ^(2)=4.908,P=0.027)。IgE介导型患儿总IgE阳性比例和牛奶蛋白sIgE阳性比例均显著高于非IgE介导型(χ^(2)=19.855,P<0.001;χ^(2)=50.077,P<0.001)。多因素Logistic回归分析结果显示,年龄<1岁(OR=4.674,95%CI:2.890~7.560)、早产(OR=3.077,95%CI:1.669~5.674)、父母有过敏史(OR=3.908,95%CI:2.236~6.830)是婴幼儿发生CMPA的危险因素(P<0.05)。结论徐州地区0~3岁婴幼儿CMPA发病率随年龄升高而降低,早产儿和父母有过敏史可导致发病率升高,且不同类型CMPA患儿的临床症状差异较大。

ILC2细胞、肠道微生态与牛奶蛋白过敏关系的研究进展

2型固有淋巴细胞(ILC2)是一种免疫细胞,可分泌辅助性T细胞2,参与呼吸道过敏、蠕虫感染等疾病的发生发展。牛奶蛋白过敏(CMPA)是一种口服耐受建立失败而引起的多器官甚至全身过敏状态。受饮食方式和环境变化的影响,肠道微生态失衡导致儿童中CMPA的发生率逐年攀升。近年来对免疫相关细胞群体的研究表明,ILC2在肠道局部免疫中起重要作用。ILC2的激活和功能表达离不开肠道菌群产生的细胞因子和代谢物,未来对过敏肠道内ILC2的代谢组学研究,或将成为治疗CMPA的靶细胞。

傅里叶变换红外光谱的牛乳中α_(s)1-酪蛋白和κ-酪蛋白含量的快速检测

为了找到一种能够对牛乳中的两种主要过敏原(αs1和κ-酪蛋白)含量快速检测的方法,以河南、湖北、宁夏和内蒙古四省区的211份中国荷斯坦牛牛乳样本为研究对象,建立了基于傅里叶变换中红外光谱技术的牛乳中αs1和κ-酪蛋白含量的无损快速检测模型。首先对牛乳的原始光谱进行预分析,发现水对牛乳的光谱吸收具有很强的干扰,对水的两个主要吸收区域1597~1712和3024~3680 cm^(-1)进行分析,发现水的吸收区域1597~1712 cm^(-1)和蛋白的部分吸收区域1558~1705 cm^(-1)(酰胺Ⅰ)基本重合,通过对比去除1597~1712 cm^(-1)前后的效果,最终选择925.92~3005.382 cm^(-1)的光谱区域作为敏感波段用于后续分析。选取的全光谱经手动降维,利用MCCV剔除异常样本,分别采用标准正态变量变换(SNV)、多元散射校正(MSC)等8种预处理算法和竞争性自适应重加权算法(CARS)、无信息变量消除法(UVE)等3种特征选择算法联合建立支持向量机回归模型(SVR)。经检验,对于αs1-酪蛋白,一阶导数和CARS算法结合建立的SVR模型效果最优,训练集相关系数Rc和测试集相关系数R p分别为0.8827和0.8998,训练集均方根误差RMSEC和测试集均方根误差RMSEP分别为1.1363和1.3726;对于κ-酪蛋白,一阶差分和UVE算法结合建立的SVR模型效果最优,训练集相关系数R_(c)和测试集相关系数R_(p)分别为0.8808和0.8903,训练集均方根误差RMSEC和测试集均方根误差RMSEP分别为0.5345和0.5354。研究结果表明,基于傅里叶变换中红外光谱技术建立的SVR模型可以对牛乳中的过敏原α_(s)1和κ-酪蛋白含量进行无损检测,预测效果良好,此研究弥补了国内利用光谱技术对牛乳中的酪蛋白进行无损快速检测的空白。

Milk protein IgG and IgA:The association with milk-induced gastrointestinal symptoms in adults

AIM:To study the association between serum levels of milk protein IgG and IgA antibodies and milk-related gastrointestinal symptoms in adults.METHODS:Milk protein IgG and IgA antibodies were determined in serum samples of 400 subjects from five outpatient clinics in Southern Finland.Subjects were randomly selected from a total of 1900 adults undergoing laboratory investigations in primary care.All 400 participants had completed a questionnaire on abdominal symptoms and dairy consumption while waiting for the laboratory visit.The questionnaire covered the nature and frequency of gastrointestinal problems,the provoking food items,family history and allergies.Twelve serum samples were disqualifi ed due to insuff icient amount of sera.The levels of specif ic milk protein IgG and IgA were measured by using the ELISA technique.The association of the milk protein-specific antibody level was studied in relation to the milk-related gastrointestinal symptoms and dairy consumption.RESULTS:Subjects drinking milk(n=265) had higher levels of milk protein IgG in their sera than non-milk drinkers(n=123,P<0.001).Subjects with gastrointestinal problems related to milk drinking(n=119) consumed less milk but had higher milk protein IgG levels than those with no milk-related gastrointestinal symptoms(n=198,P=0.02).Among the symptomatic subjects,those reporting dyspeptic symptoms had lower milk protein IgG levels than non-dyspeptics(P<0.05).However,dyspepsia was not associated with milk drinking(P=0.5).The association of high milk protein IgG levels with constipation was close to the level of statistical signif icance.Diarrhea had no association with milk protein IgG level(P=0.5).With regard to minor symptoms,flatulence and bloating(P=0.8),were not associated with milk protein IgG level.Milk protein IgA levels did not show any association with milk drinking or abdominal symptoms.The levels of milk protein IgA and IgG declined as the age of the subjects increased(P<0.004).CONCLUSION:Milk protein IgG but not milk IgA seems to be associated with self-reported milk-induced gastrointestinal symptoms.

基于B/S模式的奶牛日粮诊断系统的实现

针对现有奶牛日粮诊断过程中只考虑日粮营养组分方面的因素造成的局限性,首次提出了将奶牛日粮营养组分与营养代谢性病两个因素综合考虑,并以此结果对日粮配方优化设计。基于web2.0技术,采用JSP+Tomcat+MySQL架构,建立了B/S(浏览器/服务器)模式的奶牛日粮诊断系统。该系统先进实用,能有效地解决奶牛日粮配方针对性不强、难以规避奶牛营养性疾病等问题。

Milk Consumption and Lactose Intolerance in Adults

Objective To investigate relations between milk consumption and lactose intolerance （LI） in adults and to explore the effect of milk consumption on lactase activity.Methods Total of 182 subjects aged 20‐70 years were recruited and interviewed by questionnaires,and their accumulative cow＇s milk intake （AMI） was calculated.LI was evaluated by hydrogen breath test （HBT）.Results A negative correlation was found between AMI and severity of observed LI symptom （r=-0.2884;P0.05）.Binary logistic regression analysis showed a negative correlation between LI and duration and frequency of milk consumption （OR,0.317 and 0.465,respectively;both P0.05） and a positive correlation between LI and amount of milk consumed per sitting （OR,6.337;P0.05）.Conclusion LI is related to various milk consumption behaviors.Most Chinese adults with LI may tolerate moderate milk consumption 160 mL.

Severe dystrophy in DiGeorge syndrome

We present the case history of a 3-year-old girl who was examined because of severe dystrophy.In the background,cow’s milk allergy was found,but her body weight was unchanged after eliminating milk from her diet.Other types of malabsorption were excluded.Based on nasal regurgitation and facial dysmorphisms,the possibility of DiGeorge syndrome was suspected and was confirmed by fluorescence in situ hybridization.The authors suggest a new feature associated with DiGeorge syndrome.