Maternal Allergy and the Presence of Nonhuman Proteinaceous Molecules in Human Milk

Human milk contains proteins and/or protein fragments that originate from nonhuman organisms. These proteinaceous molecules, of which the secretion might be related to the mother’s allergy status, could be involved in the development of the immune system of the infant. This may lead, for example, to sensitization or the induction of allergen-specific tolerance. The aim of this study was to investigate the relation between maternal allergy and the levels of nonhuman proteinaceous molecules in their milk. In this study, we analysed trypsin-digested human milk serum proteins of 10 allergic mothers and 10 nonallergic mothers. A search was carried out to identify peptide sequences originating from bovine or other allergenic proteins. Several methods were applied to confirm the identification of these sequences, and the differences between both groups were investigated. Out of the 78 identified nonhuman peptide sequences, 62 sequences matched Bos taurus proteins. Eight peptide sequences of bovine β-lactoglobulin had significantly higher levels in milk from allergic mothers than in milk from nonallergic mothers. Dietary bovine β-lactoglobulin may be absorbed through the intestinal barrier and secreted into human milk. This seems to be significantly higher in allergic mothers and might have consequences for the development of the immune system of their breastfed infant.

[1]  Lennart Martens,et al.  Anatomy and evolution of database search engines-a central component of mass spectrometry based proteomic workflows. , 2020, Mass spectrometry reviews.

[2]  G. Mamone,et al.  Excretion of Dietary Cow's Milk Derived Peptides Into Breast Milk , 2019, Front. Nutr..

[3]  A. Ponsonby,et al.  Early Exposure to Cow's Milk Protein Is Associated with a Reduced Risk of Cow's Milk Allergic Outcomes. , 2019, The journal of allergy and clinical immunology. In practice.

[4]  Henk W. P. van den Toorn,et al.  Discovery and Quantification of Nonhuman Proteins in Human Milk , 2018, Journal of proteome research.

[5]  T. Matsuda,et al.  Apical-to-basolateral transepithelial transport of cow’s milk caseins by intestinal Caco-2 cell monolayers: MS-based quantitation of cellularly degraded &agr;- and &bgr;-casein fragments , 2018, Journal of biochemistry.

[6]  R. Sivamani,et al.  Epithelial barrier dysfunctions in atopic dermatitis: a skin–gut–lung model linking microbiome alteration and immune dysregulation , 2018, The British journal of dermatology.

[7]  J. Garssen,et al.  Identification of peptides with tolerogenic potential in a hydrolysed whey‐based infant formula , 2018, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[8]  L. V. Sexto,et al.  Suspected severe acute food protein-induced enterocolitis syndrome caused by cow's milk through breast milk. , 2018 .

[9]  C. Gaudichon,et al.  Protein degradation and peptide release from milk proteins in human jejunum. Comparison with in vitro gastrointestinal simulation. , 2018, Food chemistry.

[10]  S. Benjaponpitak,et al.  Detection of β-lactoglobulin in human breast-milk 7 days after cow milk ingestion , 2017, Paediatrics and international child health.

[11]  P. Ferranti,et al.  Antibody-independent identification of bovine milk-derived peptides in breast-milk. , 2016, Food & Function.

[12]  U. Jappe,et al.  Prospective investigation on the transfer of Ara h 2, the most potent peanut allergen, in human breast milk , 2016, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[13]  V. Verhasselt,et al.  Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction , 2015, Gut.

[14]  J. Cuesta-Herranz,et al.  Sensitive detection of major food allergens in breast milk: first gateway for allergenic contact during breastfeeding , 2015, Allergy.

[15]  Allan Linneberg,et al.  Respiratory allergy caused by house dust mites: What do we really know? , 2015, The Journal of allergy and clinical immunology.

[16]  D. Postma,et al.  Difference in the Breast Milk Proteome between Allergic and Non-Allergic Mothers , 2015, PloS one.

[17]  S. Miceli Sopo,et al.  Chronic Food Protein-Induced Enterocolitis Syndrome Caused by Cow's Milk Proteins Passed through Breast Milk , 2014, International Archives of Allergy and Immunology.

[18]  D. Postma,et al.  Cohort profile: the prevention and incidence of asthma and mite allergy (PIAMA) birth cohort. , 2014, International journal of epidemiology.

[19]  M. Raulf,et al.  Animal Allergens and Their Presence in the Environment , 2014, Front. Immunol..

[20]  I. Annesi-Maesano,et al.  Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma , 2014, Allergy.

[21]  Cathy H. Wu,et al.  A fast Peptide Match service for UniProt Knowledgebase , 2013, Bioinform..

[22]  A. Conti,et al.  Detection of cow’s milk proteins and minor components in human milk using proteomics techniques , 2012, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[23]  G. D'Amato,et al.  Role of Sensitization to Mammalian Serum Albumin in Allergic Disease , 2011, Current allergy and asthma reports.

[24]  A. Scaloni,et al.  The bovine milk proteome: cherishing, nourishing and fostering molecular complexity. An interactomics and functional overview. , 2011, Molecular bioSystems.

[25]  B. Finlay,et al.  The future of mucosal immunology: studying an integrated system-wide organ , 2010, Nature Immunology.

[26]  Lello Zolla,et al.  Human milk proteins: an interactomics and updated functional overview. , 2010, Journal of proteome research.

[27]  N. Cerf-Bensussan,et al.  Multiple facets of intestinal permeability and epithelial handling of dietary antigens , 2010, Mucosal Immunology.

[28]  M. Mann,et al.  MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification , 2008, Nature Biotechnology.

[29]  V. Verhasselt,et al.  Breast milk–mediated transfer of an antigen induces tolerance and protection from allergic asthma , 2008, Nature Medicine.

[30]  A. Cripps,et al.  Enterocyte and M-cell transport of native and heat-denatured bovine beta-lactoglobulin: significance of heat denaturation. , 2006, Journal of agricultural and food chemistry.

[31]  K. Grimshaw,et al.  Exposure of the fetus and infant to hens' egg ovalbumin via the placenta and breast milk in relation to maternal intake of dietary egg , 2005, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[32]  M. Neville,et al.  Albumin transcytosis across the epithelium of the lactating mouse mammary gland , 2004, The Journal of physiology.

[33]  N. Brousse,et al.  Food Allergens Are Protected from Degradation during CD23-Mediated Transepithelial Transport , 2004, International Archives of Allergy and Immunology.

[34]  B. V. Pedersen,et al.  Mammary epithelial paracellular permeability in atopic and non‐atopic mothers versus childhood atopy , 2004, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[35]  Z. Hijazi,et al.  Intestinal permeability is increased in bronchial asthma , 2004, Archives of Disease in Childhood.

[36]  Bert Brunekreef,et al.  The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study: Design and first results , 2002, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[37]  A. Plebani,et al.  Evaluation of the presence of bovine proteins in human milk as a possible cause of allergic symptoms in breast-fed children. , 2000, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[38]  M. Añón,et al.  Presence of high levels of non-degraded gliadin in breast milk from healthy mothers. , 1998, Scandinavian journal of gastroenterology.

[39]  D. Huglo,et al.  Increased intestinal permeability in bronchial asthma. , 1996, The Journal of allergy and clinical immunology.

[40]  E. Isolauri,et al.  Evaluation of the gut mucosal barrier: evidence for increased antigen transfer in children with atopic eczema. , 1996, The Journal of allergy and clinical immunology.

[41]  R. Sorva,et al.  β-Lactoglobulin secretion in human milk varies widely after cow's milk ingestion in mothers of infants with cow's milk allergy , 1994 .

[42]  C. Caffarelli,et al.  Elimination diet and intestinal permeability in atopic eczema: a preliminary study , 1993, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[43]  A. Høst,et al.  Bovine β‐1actoglobulin in human milk from atopic and non‐atopic mothers. Relationship to maternal intake of homogenized and unhomogenized milk , 1990, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[44]  I. Jakobsson,et al.  Bovine β‐Lactoglobulin in the Human Milk , 1986 .

[45]  K. Isselbacher,et al.  Protein uptake by the intestine: evidence for absorption of intact macromolecules. , 1974, Gastroenterology.

[46]  K. Verhoeckx,et al.  Protein transport across the small intestine in food allergy. , 2014, Molecular nutrition & food research.

[47]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[48]  Efsa Publication,et al.  EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on Dietary Reference Values for protein , 2012 .

[49]  M. Giuffrida,et al.  Absence in human milk of bovine beta-lactoglobulin ingested by the mother. Unreliability of ELISA measurements. , 1997, Acta bio-medica de L'Ateneo parmense : organo della Societa di medicina e scienze naturali di Parma.

[50]  D. Tomé,et al.  Transport of β-lactoglobulin and α-lactalbumin in enterocyte-like Caco-2 cells , 1995 .

[51]  I. Jakobsson,et al.  Bovine beta-lactoglobulin in the human milk. A longitudinal study during the whole lactation period. , 1986, Acta paediatrica Scandinavica.

[52]  A. Cant,et al.  The passage of maternal dietary proteins into human breast milk. , 1984, International archives of allergy and applied immunology.