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Background: Multiple studies have demonstrated associations between the early-life gut microbiome and incidence of inflammatory and autoimmune disease in childhood. Although microbial colonization is necessary for proper immune education, it is not well understood at a mechanistic level how specific communities of bacteria promote immune maturation or drive immune dysfunction in infancy., Objectives: In this study, we aimed to assess whether infant microbial communities with different overall structures differentially influence immune and gastrointestinal development in healthy mice., Methods: Germ-free mice were inoculated with fecal slurries from Bifidobacterium longum subspecies infantis positive (BIP) or B. longum subspecies infantis negative (BIN) breastfed infants; half of the mice in each group were also supplemented with a pool of human milk oligosaccharides (HMOs) for 14 d. Cecal microbiome composition and metabolite production, systemic and mucosal immune outcomes, and intestinal morphology were assessed at the end of the study., Results: The results showed that inoculation with a BIP microbiome results in a remarkably distinct microbial community characterized by higher relative abundances of cecal Clostridium senu stricto, Ruminococcus gnavus, Cellulosilyticum sp., and Erysipelatoclostridium sp. The BIP microbiome produced 2-fold higher concentrations of cecal butyrate, promoted branched short-chain fatty acid (SCFA) production, and further modulated serotonin, kynurenine, and indole metabolism relative to BIN mice. Further, the BIP microbiome increased the proportions of innate and adaptive immune cells in spleen, while HMO supplementation increased proliferation of mesenteric lymph node cells to phorbol myristate acetate and lipopolysaccharide and increased serum IgA and IgG concentrations., Conclusions: Different microbiome compositions and HMO supplementation can modulate SCFA and tryptophan metabolism and innate and adaptive immunity in young, healthy mice, with potentially important implications for early childhood health., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

BACKGROUNDThe use of high-throughput technologies has enabled rapid advancement in the knowledge of host immune responses to pathogens. Our objective was to compare the repertoire, protection, and maternal factors associated with human milk antibodies to infectious pathogens in different economic and geographic locations.METHODSUsing multipathogen protein microarrays, 878 milk and 94 paired serum samples collected from 695 women in 5 high and low-to-middle income countries (Bangladesh, Finland, Peru, Pakistan, and the United States) were assessed for specific IgA and IgG antibodies to 1,607 proteins from 30 enteric, respiratory, and bloodborne pathogens.RESULTSThe antibody coverage across enteric and respiratory pathogens was highest in Bangladeshi and Pakistani cohorts and lowest in the U.S. and Finland. While some pathogens induced a dominant IgA response (Campylobacter, Klebsiella, Acinetobacter, Cryptosporidium, and pertussis), others elicited both IgA and IgG antibodies in milk and serum, possibly related to the invasiveness of the infection (Shigella, enteropathogenic E. coli "EPEC", Streptococcus pneumoniae, Staphylococcus aureus, and Group B Streptococcus). Besides the differences between economic regions and decreases in concentrations over time, human milk IgA and IgG antibody concentrations were lower in mothers with high BMI and higher parity, respectively. In Bangladeshi infants, a higher specific IgA concentration in human milk was associated with delayed time to rotavirus infection, implying protective properties of antirotavirus antibodies, whereas a higher IgA antibody concentration was associated with greater incidence of Campylobacter infection.CONCLUSIONThis comprehensive assessment of human milk antibody profiles may be used to guide the development of passive protection strategies against infant morbidity and mortality.FUNDINGBill and Melinda Gates Foundation grant OPP1172222 (to KMJ); Bill and Melinda Gates Foundation grant OPP1066764 funded the MDIG trial (to DER); University of Rochester CTSI and Environmental Health Sciences Center funded the Rochester Lifestyle study (to RJL); and R01 AI043596 funded PROVIDE (to WAP).

Human milk (HM) components affect immune cell toll-like receptor 4 (TLR4) signaling. However, studies examining the immunomodulatory impacts of HM on TLR4 signaling in intestinal epithelial cells (IECs) are limited. This study utilized both a TLR4 reporter cell line and a Caco-2 IEC model to examine the effects of HM on lipopolysaccharide (LPS)-induced TLR4 activation and cytokine responses, respectively. Additionally, we performed fast protein liquid chromatography and mass spectrometry to identify a HM component that contributes to the effect of HM on LPS/TLR4 signaling. HM enhances LPS-induced TLR4 signaling as well as LPS-induced IEC gene expression of pro-inflammatory cytokines and negative regulators of NF-κB. Human serum albumin (HSA) present in HM contributes to these effects. HSA within HM synergizes with LPS to induce IEC gene expression of pro-inflammatory cytokines and negative regulators of NF-κB. Altogether, this study provides mechanistic evidence behind the immunomodulatory function of HM on IECs, which may contribute to an enhanced immune response in breast-fed neonates., (© 2024. The Author(s).)

Establishment of the gut microbiome during early life is a complex process with lasting implications for an individual's health. Several factors influence microbial assembly; however, breast-feeding is recognized as one of the most influential drivers of gut microbiome composition during infancy, with potential implications for function. Differences in gut microbial communities between breast-fed and formula-fed infants have been consistently observed and are hypothesized to partially mediate the relationships between breast-feeding and decreased risk for numerous communicable and noncommunicable diseases in early life. Despite decades of research on the gut microbiome of breast-fed infants, there are large scientific gaps in understanding how human milk has evolved to support microbial and immune development. This review will summarize the evidence on how breast-feeding broadly affects the composition and function of the early-life gut microbiome and discuss mechanisms by which specific human milk components shape intestinal bacterial colonization, succession, and function., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Traditional farming lifestyle has been shown to be protective against asthma and allergic diseases. The individual factors that appear to be associated with this "farm-life effect" include consumption of unpasteurized farm milk and exposure to farm animals and stables. However, the biomarkers of the protective immunity and those associated with early development of allergic diseases in infancy remain unclear. The "Zooming in to Old Order Mennonites (ZOOM)" study was designed to assess the differences in the lifestyle and the development of the microbiome, systemic and mucosal immunity between infants born to traditional farming lifestyle at low risk for allergic diseases and those born to urban/suburban atopic families with a high risk for allergic diseases in order to identify biomarkers of development of allergic diseases in infancy. 190 mothers and their infants born to Old Order Mennonite population protected from or in Rochester families at high risk for allergic diseases were recruited before birth from the Finger Lakes Region of New York State. Questionnaires and samples are collected from mothers during pregnancy and after delivery and from infants at birth and at 1-2 weeks, 6 weeks, 6, 12, 18, and 24 months, with 3-, 4-, and 5-year follow-up ongoing. Samples collected include maternal blood, stool, saliva, nasal and skin swabs and urine during pregnancy; breast milk postnatally; infant blood, stool, saliva, nasal and skin swabs. Signs and symptoms of allergic diseases are assessed at every visit and serum specific IgE is measured at 1 and 2 years of age. Allergic diseases are diagnosed by clinical history, exam, and sensitization by skin prick test and/or serum specific IgE. By the end of the first year of life, the prevalence of food allergy and atopic dermatitis were higher in ROC infants compared to the rates observed in OOM infants as was the number of infants sensitized to foods. These studies of immune system development in a population protected from and in those at risk for allergic diseases will provide critical new knowledge about the development of the mucosal and systemic immunity and lay the groundwork for future studies of prevention of allergic diseases., Competing Interests: KJ has received research funding from Janssen Research & Development, Food Allergy Research and Education and Aimmune. She is a consultant for DBV Technologies and Janssen and received royalties from Up-To-Date and declares no other conflicts of interest. Other authors declare no conflicts of interest., (Copyright © 2022 Järvinen, Davis, Bevec, Jackson, Pizzarello, Catlin, Klein, Sunkara, Diaz, Miller, Martina, Thakar, Seppo, Looney and the Collaborative Working Group.)

Importance: Long-term effect of parental COVID-19 infection vs vaccination on human milk antibody composition and functional activity remains unclear., Objective: To compare temporal IgA and IgG response in human milk and microneutralization activity against SARS-CoV-2 between lactating parents with infection and vaccinated lactating parents out to 90 days after infection or vaccination., Design, Setting, and Participants: Convenience sampling observational cohort (recruited July to December 2020) of lactating parents with infection with human milk samples collected at days 0 (within 14 days of diagnosis), 3, 7, 10, 28, and 90. The observational cohort included vaccinated lactating parents with human milk collected prevaccination, 18 days after the first dose, and 18 and 90 days after the second dose., Exposures: COVID-19 infection diagnosed by polymerase chain reaction within 14 days of consent or receipt of messenger RNA (mRNA) COVID-19 vaccine (BNT162b2 or mRNA-1273)., Main Outcomes and Measures: Human milk anti-SARS-CoV-2 receptor-binding domain IgA and IgG and microneutralization activity against live SARS-CoV-2 virus., Results: Of 77 individuals, 47 (61.0%) were in the infection group (mean [SD] age, 29.9 [4.4] years), and 30 (39.0%) were in the vaccinated group (mean [SD] age, 33.0 [3.4] years; P = .002). The mean (SD) age of infants in the infection and vaccinated group were 3.1 (2.2) months and 7.5 (5.2) months, respectively (P < .001). Infection was associated with a variable human milk IgA and IgG receptor-binding domain-specific antibody response over time that was classified into different temporal patterns: upward trend and level trend (33 of 45 participants [73%]) and low/no response (12 of 45 participants [27%]). Infection was associated with a robust and quick IgA response in human milk that was stable out to 90 days after diagnosis. Vaccination was associated with a more uniform IgG-dominant response with concentrations increasing after each vaccine dose and beginning to decline by 90 days after the second dose. Vaccination was associated with increased human milk IgA after the first dose only (mean [SD] increase, 31.5 [32.6] antibody units). Human milk collected after infection and vaccination exhibited microneutralization activity. Microneutralization activity increased throughout time in the vaccine group only (median [IQR], 2.2 [0] before vaccine vs 10 [4.0] after the first dose; P = .003) but was higher in the infection group (median [IQR], 20 [67] at day 28) vs the vaccination group after the first-dose human milk samples (P = .002). Both IgA and non-IgA (IgG-containing) fractions of human milk from both participants with infection and those who were vaccinated exhibited microneutralization activity against SARS-CoV-2., Conclusions and Relevance: In this cohort study of a convenience sample of lactating parents, the pattern of IgA and IgG antibodies in human milk differed between COVID-19 infection vs mRNA vaccination out to 90 days. While infection was associated with a highly variable IgA-dominant response and vaccination was associated with an IgG-dominant response, both were associated with having human milk that exhibited neutralization activity against live SARS-CoV-2 virus.

Background: Limited data are available regarding the balance of risks and benefits from human milk and/or breastfeeding during and following maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Objective: To investigate whether SARS-CoV-2 can be detected in milk and on the breast after maternal coronavirus disease 2019 (COVID-19) diagnosis; and characterize concentrations of milk immunoglobulin (Ig) A specific to the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) during the 2 months after onset of symptoms or positive diagnostic test., Methods: Using a longitudinal study design, we collected milk and breast skin swabs one to seven times from 64 lactating women with COVID-19 over a 2-month period, beginning as early as the week of diagnosis. Milk and breast swabs were analyzed for SARS-CoV-2 RNA, and milk was tested for anti-RBD IgA., Results: SARS-CoV-2 was not detected in any milk sample or on 71% of breast swabs. Twenty-seven out of 29 (93%) breast swabs collected after breast washing tested negative for SARS-CoV-2. Detection of SARS-CoV-2 on the breast was associated with maternal coughing and other household COVID-19. Most (75%; 95% CI, 70-79%; n=316) milk samples contained anti-RBD IgA, and concentrations increased ( P =.02) during the first two weeks following onset of COVID-19 symptoms or positive test. Milk-borne anti-RBD IgA persisted for at least two months in 77% of women., Conclusion: Milk produced by women with COVID-19 does not contain SARS-CoV-2 and is likely a lasting source of passive immunity via anti-RBD IgA. These results support recommendations encouraging lactating women to continue breastfeeding during and after COVID-19 illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pace, Williams, Järvinen, Meehan, Martin, Ley, Barbosa-Leiker, Andres, Yeruva, Belfort, Caffé, Navarrete, Lackey, Pace, Gogel, Fehrenkamp, Klein, Young, Rosen-Carole, Diaz, Gaw, Flaherman, McGuire, McGuire and Seppo.)

Background: Growing up on traditional, single-family farms is associated with protection against asthma in school age, but the mechanisms against early manifestations of atopic disease are largely unknown. We sought determine the gut microbiome and metabolome composition in rural Old Order Mennonite (OOM) infants at low risk and Rochester, NY urban/suburban infants at high risk for atopic diseases., Methods: In a cohort of 65 OOM and 39 Rochester mother-infant pairs, 101 infant stool and 61 human milk samples were assessed by 16S rRNA gene sequencing for microbiome composition and qPCR to quantify Bifidobacterium spp. and B. longum ssp. infantis (B. infantis), a consumer of human milk oligosaccharides (HMOs). Fatty acids (FAs) were analyzed in 34 stool and human 24 milk samples. Diagnoses and symptoms of atopic diseases by 3 years of age were assessed by telephone., Results: At a median age of 2 months, stool was enriched with Bifidobacteriaceae, Clostridiaceae, and Aerococcaceae in the OOM compared with Rochester infants. B. infantis was more abundant (p < .001) and prevalent, detected in 70% of OOM compared with 21% of Rochester infants (p < .001). Stool colonized with B. infantis had higher levels of lactate and several medium- to long/odd-chain FAs. In contrast, paired human milk was enriched with a distinct set of FAs including butyrate. Atopic diseases were reported in 6.5% of OOM and 35% of Rochester children (p < .001)., Conclusion: A high rate of B. infantis colonization, similar to that seen in developing countries, is found in the OOM at low risk for atopic diseases., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: In addition to farming exposures in childhood, maternal farming exposures provide strong protection against allergic disease in their children; however, the effect of farming lifestyle on human milk (HM) composition is unknown., Objective: This study aims to characterize the maternal immune effects of Old Order Mennonite (OOM) traditional farming lifestyle when compared with Rochester (ROC) families at higher risk for asthma and allergic diseases using HM as a proxy., Methods: HM samples collected at median 2 months of lactation from 52 OOM and 29 ROC mothers were assayed for IgA 1 and IgA 2 antibodies, cytokines, endotoxin, HM oligosaccharides (HMOs), and targeted fatty acid (FA) metabolites. Development of early childhood atopic diseases in children by 3 years of age was assessed. In addition to group comparisons, systems level network analysis was performed to identify communities of multiple HM factors in ROC and OOM lifestyle., Results: HM contains IgA 1 and IgA 2 antibodies broadly recognizing food, inhalant, and bacterial antigens. OOM HM has significantly higher levels of IgA to peanut, ovalbumin, dust mites, and Streptococcus equii as well TGF-β2, and IFN-λ3. A strong correlation occurred between maternal antibiotic use and levels of several HMOs. Path-based analysis of HMOs shows lower activity in the path involving lactoneohexaose (LNH) in the OOM as well as higher levels of lacto- N -neotetraose (LNnT) and two long-chain FAs C-18OH (stearic acid) and C-23OH (tricosanoic acid) compared with Rochester HM. OOM and Rochester milk formed five different clusters, e.g., butyrate production was associated with Prevotellaceae , Veillonellaceae , and Micrococcaceae cluster. Development of atopic disease in early childhood was more common in Rochester and associated with lower levels of total IgA, IgA 2 to dust mite, as well as of TSLP., Conclusion: Traditional, agrarian lifestyle, and antibiotic use are strong regulators of maternally derived immune and metabolic factors, which may have downstream implications for postnatal developmental programming of infant's gut microbiome and immune system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Seppo, Choudhury, Pizzarello, Palli, Fridy, Rajani, Stern, Martina, Yonemitsu, Bode, Bu, Tamburini, Piras, Wallach, Allen, Looney, Clemente, Thakar and Järvinen.)

Breastfeeding provides defense against infectious disease during early life. The mechanisms underlying this protection are complex but likely include the vast array of immune cells and components, such as immunoglobulins, in milk. Simply characterizing the concentrations of these bioactives, however, provides only limited information regarding their potential relationships with disease risk in the recipient infant. Rather, understanding pathogen and antigen specificity profiles of milk-borne immunoglobulins might lead to a more complete understanding of how maternal immunity impacts infant health and wellbeing. Milk produced by women living in 11 geographically dispersed populations was applied to a protein microarray containing antigens from 16 pathogens, including diarrheagenic E. coli , Shigella spp. , Salmonella enterica serovar Typhi, Staphylococcus aureus , Streptococcus pneumoniae, Mycobacterium tuberculosis and other pathogens of global health concern, and specific IgA and IgG binding was measured. Our analysis identified novel disease-specific antigen responses and suggests that some IgA and IgG responses vary substantially within and among populations. Patterns of antibody reactivity analyzed by principal component analysis and differential reactivity analysis were associated with either lower-to-middle-income countries (LMICs) or high-income countries (HICs). Antibody levels were generally higher in LMICs than HICs, particularly for Shigella and diarrheagenic E. coli antigens, although sets of S. aureus , S. pneumoniae , and some M. tuberculosis antigens were more reactive in HICs. Differential responses were typically specific to canonical immunodominant antigens, but a set of nondifferential but highly reactive antibodies were specific to antigens possibly universally recognized by antibodies in human milk. This approach provides a promising means to understand how breastfeeding and human milk protect (or do not protect) infants from environmentally relevant pathogens. Furthermore, this approach might lead to interventions to boost population-specific immunity in at-risk breastfeeding mothers and their infants., Competing Interests: AR and JC are employees of Antigen Discovery Incorporated, a company that carries patents related to the protein array analyses used here and the location where the arrays were conducted. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 McGuire, Randall, Seppo, Järvinen, Meehan, Gindola, Williams, Sellen, Kamau-Mbuthia, Kamundia, Mbugua, Moore, Prentice, Foster, Otoo, Rodríguez, Pareja, Bode, McGuire and Campo.)

The novel coronavirus SARS-CoV-2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS-CoV-2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS-CoV in human milk (it was negative); and no published data on MERS-CoV and human milk. We identified 13 studies reporting human milk tested for SARS-CoV-2; one study (a non-peer-reviewed preprint) detected the virus in one milk sample, and another study detected SARS-CoV-2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed., (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: During early life, systemic protection to influenza is passively provided by transplacental transfer of IgG antibodies and oral and gastrointestinal mucosal protection via breast milk (BM) containing predominantly IgA. Immune imprinting, influenced by initial exposure of the infant immune system to influenza, has recently been recognized as an important determinant of future influenza immune responses. Methods: We utilized stored frozen BM from a prospective birth cohort to assess immune factors in human milk. The earliest available BM and a paired, timed serum sample was assessed from each of  7 mothers. Paired infant serum samples were assayed at up to three time points during the first 12 months of life, one prior to assumed disappearance of transplacentally transferred IgG, and one after. We utilized a novel multiplex assay to assess mothers' and infants' IgG and IgA antibodies in serum to a panel of  30 individual recombinant hemagglutinin (rHA) proteins of influenza virus strains and chimeric rHAs. We also characterized IgA and IgG antibody levels in breast milk which provide mucosal protection. Results:  Our pilot results, analyzing a small number of samples demonstrate the feasibility of this method for studying paired maternal-infant IgG and IgA anti-influenza immunity patterns. Unlike IgG antibodies, breast milk influenza virus HA-specific IgA antibody levels and patterns were mostly discordant compared to serum.  As expected, there was a steady decay of infant influenza specific IgG levels by 6 to 8 months of age, which was not, however, comparable in all infants. In contrast, most of the infants showed an increase in IgA responses throughout the first year of life Conclusions:   This new analytical method can be applied in a larger study to understand the impact of maternal imprinting on influenza immunity., Competing Interests: No competing interests were disclosed.

Background: During early life, systemic protection to influenza is passively provided by transplacental transfer of IgG antibodies and oral and gastrointestinal mucosal protection via breast milk (BM) containing predominantly IgA. Immune imprinting, influenced by initial exposure of the infant immune system to influenza, has recently been recognized as an important determinant of future influenza immune responses. Methods: We utilized stored frozen BM from a prospective birth cohort to assess immune factors in human milk. The earliest available BM and a paired, timed serum sample was assessed from each of  7 mothers. Paired infant serum samples were assayed at up to three time points during the first 12 months of life, one prior to assumed disappearance of transplacentally transferred IgG, and one after. We utilized a novel multiplex assay to assess mothers' and infants' IgG and IgA antibodies in serum to a panel of  30 individual recombinant hemagglutinin (rHA) proteins of influenza virus strains and chimeric rHAs. We also characterized IgA and IgG antibody levels in breast milk providing mucosal protection. Results:  Our pilot results, analyzing a small number of samples demonstrate the feasibility of this method for studying paired maternal-infant IgG and IgA anti-influenza immunity patterns. Unlike IgG antibodies, breast milk influenza virus HA-specific IgA antibody levels and patterns were mostly discordant compared to serum.  As expected, there was a steady decay of infant influenza specific IgG levels by 6 to 8 months of age, which was not, however, comparable in all infants. In contrast, most of the infants showed an increase in IgA responses throughout the first year of life Conclusions:   This new analytical method can be applied in a larger study to understand the impact of maternal imprinting on influenza immunity., Competing Interests: No competing interests were disclosed.

Breast-feeding is currently recommended to prevent the development of allergic diseases; however, data are conflicting and mechanisms are unclear. The immunomodulatory composition of human milk is poorly characterized and varies between mothers. We and others have shown that high levels of human milk IgA and certain cytokines and human milk oligosaccharides are associated with protection against food allergy in the infant, but it is unclear whether they are responsible for or simply biomarkers of the vertical transfer of protection. Because human milk has pre- and probiotic properties, the anti-allergy protection afforded by human milk may be due to its control on the developing gut microbiome. In mice, murine milk IgA supports gut homeostasis and shapes the microbiota, which in turn diversifies the intestinal IgA repertoire that reciprocally promotes the diversity of gut microbiome; these mechanisms are poorly understood in humans. In addition, several human milk bioactives are immunostimulatory, which may in part provide protection against allergic diseases. The regulation of immunologically active components in human milk is incompletely understood, although accumulating evidence suggests that IgA and cytokines in human milk reflect maternal exposures. This review summarizes the current literature on human milk components that have been associated with protection against food allergy and related allergic disorders in early childhood and discusses the work relating to regulation of these levels in human milk and possible mechanisms of action.

Background: We have previously shown that maternal cow's milk (CM) elimination results in downregulation of CM-specific IgA antibody levels in BM, but not in serum, suggesting that an entero-mammary link may exist for food-specific antibody-secreting cells., Objective: We sought to investigate whether food-specific IgA epitope profiles differ intra-individually between mother's serum and BM. We also examined how infants' food epitope-specific IgA develops in early infancy and the relationship of IgA epitope recognition with development of cow's milk allergy (CMA)., Methods: We measured specific IgA to a series of overlapping peptides in major CM allergens (α s1 -, α s2 -, β- and κ-caseins and β-lactoglobulin) in paired maternal and infant serum as well as BM samples in 31 mother-infant dyads within the first 15 post-partum months utilizing peptide microarray., Results: There was significant discordance in epitope specificity between BM and maternal sera ranging from only 13% of sample pairs sharing at least one epitope in α s1 -casein to 73% in κ-casein. Epitope-specific IgA was detectable in infants' sera starting at less than 3 months of age. Sera of mothers with a CMA infant had increased binding of epitope-specific IgA to CM proteins compared to those with a non-CMA infant., Conclusion & Clinical Relevance: These findings support the concept that mother's milk has a distinct antifood antibody repertoire when compared to the antibody repertoire of the peripheral blood. Increased binding of serum epitope-specific IgA to CM in mothers of infants with CMA may reflect inherited systemic immunogenicity of CM proteins in these families, although specific IgA in breast milk was not proportionally up-regulated., (© 2017 John Wiley & Sons Ltd.)

The aims of the present study were to assess whether protection against peanut (PN) sensitization can be conferred by maternal PN consumption alone and if so, whether protection was increased by mucosal adjuvant co-administration. Mice were fed with low dose of either PN or PN with cholera toxin (CT) preconceptionally, and during pregnancy and lactation. Offspring serum PN-specific immunoglobulins and cellular responses by splenocytes and mesenteric lymph node (MLN) cells were determined after an active PN sensitization protocol. Milk was collected from lactating mothers of 11-21-day-old pups for evaluation of PN-specific immunoglobulin levels. We found that offspring of PN fed mothers exhibited lower PN-specific IgE levels and reduced PN-stimulated splenocyte and MLN cells cytokine secretion than offspring of non PN fed mothers. CT co-administration with PN enhanced these responses.. Milk from mothers fed PN and CT, but not PN alone preconceptionally and during pregnancy and lactation contained markedly and significantly increased levels of both peanut-specific IgG2a and IgA. Our study demonstrated that maternal feeding of PN alone had a protective effect against PN sensitization of the progeny, which was enhanced by co-administration of a mucosal adjuvant. Increased levels of PN-specific IgG2a and/or IgA in milk were seen when PN and CT were administered together, suggesting that transmission of maternal immunoglobulins may play a role in the observed protection.