PMID- 32315306 OWN - NLM STAT- MEDLINE DCOM- 20200710 LR - 20200710 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 15 IP - 4 DP - 2020 TI - Novel approach to visualize the inter-dependencies between maternal sensitization, breast milk immune components and human milk oligosaccharides in the LIFE Child cohort. PG - e0230472 LID - 10.1371/journal.pone.0230472 [doi] LID - e0230472 AB - 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 fur 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. FAU - Michel, Loris AU - Michel L AD - Nestle Research, Vers-chez-les-Blanc, Lausanne, Switzerland. FAU - Shevlyakova, Maya AU - Shevlyakova M AD - Nestle Research, Vers-chez-les-Blanc, Lausanne, Switzerland. FAU - Ni Cleirigh, Ellen AU - Ni Cleirigh E AD - Nestle Development Centre Nutrition, Askeaton, Ireland. FAU - Eckhardt, Erik AU - Eckhardt E AD - Nestle Research, Vers-chez-les-Blanc, Lausanne, Switzerland. FAU - Holvoet, Sebastien AU - Holvoet S AD - Nestle Research, Vers-chez-les-Blanc, Lausanne, Switzerland. FAU - Nutten, Sophie AU - Nutten S AD - Nestle Research, Vers-chez-les-Blanc, Lausanne, Switzerland. FAU - Sprenger, Norbert AU - Sprenger N AD - Nestle Research, Vers-chez-les-Blanc, Lausanne, Switzerland. FAU - Korner, Antje AU - Korner A AD - Faculty of Medicine, LIFE Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany. FAU - Vogel, Mandy AU - Vogel M AD - Faculty of Medicine, LIFE Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany. FAU - Nembrini, Chiara AU - Nembrini C AD - Nestle Research, Vers-chez-les-Blanc, Lausanne, Switzerland. FAU - Kiess, Wieland AU - Kiess W AD - Faculty of Medicine, LIFE Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany. FAU - Blanchard, Carine AU - Blanchard C AUID- ORCID: 0000-0002-3377-290X AD - Nestle Research, Vers-chez-les-Blanc, Lausanne, Switzerland. LA - eng SI - ClinicalTrials.gov/NCT02550236 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200421 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Immunoglobulin A) RN - 0 (Methacrylates) RN - 0 (Oligosaccharides) RN - 37341-29-0 (Immunoglobulin E) RN - 76057-06-2 (Transforming Growth Factors) RN - 2-hydroxyethyl methacrylate sensitization SB - IM MH - Adult MH - Breast Feeding MH - Child MH - Cohort Studies MH - Dermatitis, Allergic Contact MH - Female MH - Humans MH - Immunoglobulin A/*metabolism MH - Immunoglobulin E/blood MH - Infant MH - Lactation MH - Methacrylates/adverse effects MH - Milk Hypersensitivity/*etiology MH - Milk, Human/*chemistry MH - Oligosaccharides/*metabolism MH - Principal Component Analysis/methods MH - Transforming Growth Factors/metabolism PMC - PMC7173766 COIS- WK received an unconditional grant by Societe des Produits Nestle S.A. to carry out this analysis. MS, ENC, EE, SH, SN, NS, CN and CB were employed by Societe des Produits Nestle S.A. during the conduct of the study. This does not alter the adherence to PLOS ONE policies on sharing data and materials. AK, LM, and MV have no conflict of interest to disclose for this work. Societe des Produits Nestle S.A. and authors of this publication hold patents in the context of allergy management: EE, SH, SN, NS, CN, CB. Results of the current work are not used in currently filed or published patents. EDAT- 2020/04/22 06:00 MHDA- 2020/07/11 06:00 PMCR- 2020/04/21 CRDT- 2020/04/22 06:00 PHST- 2019/06/01 00:00 [received] PHST- 2020/03/01 00:00 [accepted] PHST- 2020/04/22 06:00 [entrez] PHST- 2020/04/22 06:00 [pubmed] PHST- 2020/07/11 06:00 [medline] PHST- 2020/04/21 00:00 [pmc-release] AID - PONE-D-19-14657 [pii] AID - 10.1371/journal.pone.0230472 [doi] PST - epublish SO - PLoS One. 2020 Apr 21;15(4):e0230472. doi: 10.1371/journal.pone.0230472. eCollection 2020.