Dataset Information

Novel approach to visualize the inter-dependencies between maternal sensitization, breast milk immune components and human milk oligosaccharides in the LIFE Child cohort.

ABSTRACT: BACKGROUND:Numerous studies have shown that specific components of breast milk, considered separately, are associated with disease status in the mother or the child using univariate analyses. However, very few studies have considered multivariate analysis approaches to evaluate the relationship between multiple breast milk components simultaneously. AIM:Here we aimed at visualizing breast milk component complex interactions in the context of the allergy status of the mother or the child. METHODS:Milk samples were collected from lactating mothers participating in the Leipziger Forschungszentrum für Zivilisationskrankheiten (LIFE) Child cohort in Leipzig, Germany. A total of 156 breast milk samples, collected at 3 months after birth from mother/infant pairs, were analyzed for 51 breast milk components. Correlation, principal component analysis (PCA) and graphical discovery analysis were used. RESULT:Correlations ranging from 0.40 to 0.96 were observed between breast milk fatty acid and breast milk phospholipids levels and correlations ranging from 0 to 0.76 between specific human milk oligosaccharides (HMO) were observed. No separation of the data based on the risk of allergy in the infants was identified using PCA. When graphical discovery analysis was used, dependencies between maternal plasma immunoglobulin E (IgE) level and the breast milk immune marker transforming growth factor-beta 2 (TGF-ß2), between TGF-ß2, breast milk immunoglobulin A (IgA) and TGF-ß1 as well as between breast milk total protein and birth weight were observed. Graphical discovery analysis also exemplifies a possible competition for the fucosyl group between 2'FL, LNFP-I and 3'FL in the HMO group. Additionally, dependencies between immune component IgA and specific HMO (6'SL and blood group A antigen tetraose type 5 or PI-HMO) were identified. CONCLUSION:Graphical discovery analysis applied to complex matrices such as breast milk composition can aid in understanding the complexity of interactions between breast milk components and possible relations to health parameters in the mother or the infant. This approach can lead to novel discoveries in the context of health and diseases such as allergy. Our study thus represents the first attempt to visualize the complexity and the inter-dependency of breast milk components.

SUBMITTER: Michel L

PROVIDER: S-EPMC7173766 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Novel approach to visualize the inter-dependencies between maternal sensitization, breast milk immune components and human milk oligosaccharides in the LIFE Child cohort.

Michel Loris L Shevlyakova Maya M Ní Cléirigh Ellen E Eckhardt Erik E Holvoet Sebastien S Nutten Sophie S Sprenger Norbert N Körner Antje A Vogel Mandy M Nembrini Chiara C Kiess Wieland W Blanchard Carine C

PloS one 20200421 4

<h4>Background</h4>Numerous studies have shown that specific components of breast milk, considered separately, are associated with disease status in the mother or the child using univariate analyses. However, very few studies have considered multivariate analysis approaches to evaluate the relationship between multiple breast milk components simultaneously.<h4>Aim</h4>Here we aimed at visualizing breast milk component complex interactions in the context of the allergy status of the mother or the ...[more]

PMID: 32315306

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Project description:BackgroundAnalysis of allergen-specific IgE responses in birth cohorts with microarrayed allergens has provided detailed information regarding the evolution of specific IgE responses in children. High-resolution data regarding early development of allergen-specific IgG are needed.ObjectiveWe sought to analyze IgG reactivity to microarrayed allergens in mothers during pregnancy, in cord blood samples, in breast milk, and in infants in the first years of life with the aim to investigate whether maternal allergen-specific IgG can protect against IgE sensitization in the offspring.MethodsPlasma samples from mothers during the third trimester, cord blood, breast milk collected 2 months after delivery, and plasma samples from children at 6, 12, and 60 months of age were analyzed for IgG reactivity to 164 microarrayed allergens (ImmunoCAP ISAC technology) in 99 families of the Swedish birth cohort Assessment of Lifestyle and Allergic Disease During Infancy (ALADDIN). IgE sensitizations to microarrayed allergens were determined at 5 years of age in the children.ResultsAllergen-specific IgG reactivity profiles in mothers, cord blood, and breast milk were highly correlated. Maternal allergen-specific IgG persisted in some children at 6 months. Children's allergen-specific IgG production occurred at 6 months and reflected allergen exposure. Children who were IgE sensitized against an allergen at 5 years of age had significantly higher allergen-specific IgG levels than nonsensitized children. For all 164 tested allergens, children from mothers with increased (>30 ISAC standardized units) specific plasma IgG levels against an allergen had no IgE sensitizations against that allergen at 5 years of age.ConclusionThis is the first detailed analysis of the molecular IgG recognition profile in mothers and their children in early life. High allergen-specific IgG reactivity in the mother's plasma and breast milk and in cord blood seemed to protect against allergic sensitization at 5 years of age.

Project description:Background: Human milk contains many bioactive components that are typically studied in isolation, including bacteria. We performed an integrated analysis of human milk oligosaccharides and fatty acids to explore their associations with milk microbiota. Methods: We studied a sub-sample of 393 mothers in the CHILD birth cohort. Milk was collected at 3-4 months postpartum. Microbiota was analyzed by 16S rRNA gene V4 sequencing. Oligosaccharides and fatty acids were analyzed by rapid high-throughput high performance and gas liquid chromatography, respectively. Dimension reduction was performed with principal component analysis for oligosaccharides and fatty acids. Center log-ratio transformation was applied to all three components. Associations between components were assessed using Spearman rank correlation, network visualization, multivariable linear regression, redundancy analysis, and structural equation modeling. P-values were adjusted for multiple comparisons. Key covariates were considered, including fucosyltransferase-2 (FUT2) secretor status of mother and infant, method of feeding (direct breastfeeding or pumped breast milk), and maternal fish oil supplement use. Results: Overall, correlations were strongest between milk components of the same type. For example, FUT2-dependent HMOs were positively correlated with each other, and Staphylococcus was negatively correlated with other core taxa. Some associations were also observed between components of different types. Using redundancy analysis and structural equation modeling, the overall milk fatty acid profile was significantly associated with milk microbiota composition. In addition, some individual fatty acids [22:6n3 (docosahexaenoic acid), 22:5n3, 20:5n3, 17:0, 18:0] and oligosaccharides (fucosyl-lacto-N-hexaose, lacto-N-hexaose, lacto-N-fucopentaose I) were associated with microbiota α diversity, while others (C18:0, 3'-sialyllactose, disialyl-lacto-N-tetraose) were associated with overall microbiota composition. Only a few significant associations between individual HMOs and microbiota were observed; notably, among mothers using breast pumps, Bifidobacterium prevalence was associated with lower abundances of disialyl-lacto-N-hexaose. Additionally, among non-secretor mothers, Staphylococcus was positively correlated with sialylated HMOs. Conclusion: Using multiple approaches to integrate and analyse milk microbiota, oligosaccharides, and fatty acids, we observed several associations between different milk components and microbiota, some of which were modified by secretor status and/or breastfeeding practices. Additional research is needed to further validate and mechanistically characterize these associations and determine their relevance to infant gut and respiratory microbiota development and health.

Dataset Information

Novel approach to visualize the inter-dependencies between maternal sensitization, breast milk immune components and human milk oligosaccharides in the LIFE Child cohort.

Publications

Novel approach to visualize the inter-dependencies between maternal sensitization, breast milk immune components and human milk oligosaccharides in the LIFE Child cohort.

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