Influence of maternal body mass index on human milk composition and associations to infant metabolism and gut colonisation: MAINHEALTH - a study protocol for an observational birth cohort

Katrine Overgaard Poulsen, Julie Astono, Rasmus Riemer Jakobsen, Niels Uldbjerg, Jens Fuglsang, Dennis Sandris Nielsen, Ulrik Kræmer Sundekilde, Katrine Overgaard Poulsen, Julie Astono, Rasmus Riemer Jakobsen, Niels Uldbjerg, Jens Fuglsang, Dennis Sandris Nielsen, Ulrik Kræmer Sundekilde

Abstract

Introduction: Human milk provides all macronutrients for growth, bioactive compounds, micro-organisms and immunological components, which potentially interacts with and primes infant growth and, development, immune responses and the gut microbiota of the new-born. Infants with an overweight mother are more likely to become overweight later in life and overweight has been related to the gut microbiome. Therefore, it is important to investigate the mother-milk-infant triad as a biological system and if the maternal weight status influences the human milk composition, infant metabolism and gut microbiome.

Methods and analysis: This study aims to include 200 mother-infant dyads stratified into one of three body mass index (BMI) categories based on mother's prepregnancy BMI. Multiomics analyses include metabolomics, proteomics, glycomics and microbiomics methods, aiming to characterise human milk from the mothers and further relate the composition to infant gut microbiota and its metabolic impact in the infant. Infant gut microbiota is analysed using 16S sequencing of faeces samples. Nuclear magnetic resonance and mass spectrometry are used for the remaining omics analysis. We investigate whether maternal pre-pregnancy BMI results in a distinct human milk composition that potentially affects the initial priming of the infant's gut environment and metabolism early in life.

Ethics and dissemination: The Central Denmark Region Committees on Health Research Ethics has approved the protocol (J-nr. 1-10-72-296-18). All participants have before inclusion signed informed consent and deputy informed consent in accordance with the Declaration of Helsinki II. Results will be disseminated to health professionals including paediatricians, research community, nutritional policymakers, industry and finally the public. The scientific community will be informed via peer-reviewed publications and presentations at scientific conferences, the industry will be invited for meetings, and the public will be informed via reports in science magazines and the general press. Data cleared for personal data, will be deposited at public data repositories.

Trial registration number: Danish regional committee of the Central Jutland Region, journal number: 1-10-72-296-18, version 6.Danish Data Protection Agency, journal number: 2016-051-000001, 1304.

Clinicaltrials: gov, identifier: NCT05111990.

Keywords: microbiology; nutrition & dietetics; paediatrics.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

References

    1. World Health Organization . Infant and young child nutrition: global strategy on infant and young child feeding report by the Secretariat, 2002. Available: [Accessed 30 Jun 2022].
    1. Asbury MR, Butcher J, Copeland JK, et al. . Mothers of preterm infants have individualized breast milk microbiota that changes temporally based on maternal characteristics. Cell Host Microbe 2020;28:669–82. 10.1016/j.chom.2020.08.001
    1. Andreas NJ, Hyde MJ, Gomez-Romero M, et al. . Multiplatform characterization of dynamic changes in breast milk during lactation. Electrophoresis 2015;36:2269–85. 10.1002/elps.201500011
    1. Thum C, Wall C, Day L, et al. . Changes in human milk fat globule composition throughout lactation: a review. Front Nutr 2022;9:835856. 10.3389/fnut.2022.835856
    1. Karatas Z, Durmus Aydogdu S, Dinleyici EC, et al. . Breastmilk ghrelin, leptin, and fat levels changing foremilk to hindmilk: is that important for self-control of feeding? Eur J Pediatr 2011;170:1273–80. 10.1007/s00431-011-1438-1
    1. Villaseñor A, Garcia-Perez I, Garcia A, et al. . Breast milk metabolome characterization in a single-phase extraction, multiplatform analytical approach. Anal Chem 2014;86:8245–52. 10.1021/ac501853d
    1. Innis SM. Impact of maternal diet on human milk composition and neurological development of infants. Am J Clin Nutr 2014;99:734S–41. 10.3945/ajcn.113.072595
    1. Bravi F, Wiens F, Decarli A, et al. . Impact of maternal nutrition on breast-milk composition: a systematic review. Am J Clin Nutr 2016;104:646–62. 10.3945/ajcn.115.120881
    1. Lönnerdal B, Iyer S. Lactoferrin: molecular structure and biological function. Annu Rev Nutr 1995;15:93–110. 10.1146/annurev.nu.15.070195.000521
    1. Lönnerdal B. Nutritional and physiologic significance of human milk proteins. Am J Clin Nutr 2003;77:1537S–43. 10.1093/ajcn/77.6.1537S
    1. Andreas NJ, Kampmann B, Mehring Le-Doare K. Human breast milk: a review on its composition and bioactivity. Early Hum Dev 2015;91:629–35. 10.1016/j.earlhumdev.2015.08.013
    1. Guerrero A, Dallas DC, Contreras S, et al. . Mechanistic peptidomics: factors that dictate specificity in the formation of endogenous peptides in human milk. Mol Cell Proteomics 2014;13:3343–51. 10.1074/mcp.M113.036194
    1. Dallas DC, Guerrero A, Khaldi N, et al. . A peptidomic analysis of human milk digestion in the infant stomach reveals protein-specific degradation patterns. J Nutr 2014;144:815–20. 10.3945/jn.113.185793
    1. Lu J, Antunes Fernandes E, Páez Cano AE, et al. . Changes in milk proteome and metabolome associated with dry period length, energy balance, and lactation stage in postparturient dairy cows. J Proteome Res 2013;12:3288–96. 10.1021/pr4001306
    1. Grapov D, Lemay DG, Weber D, et al. . The human colostrum whey proteome is altered in gestational diabetes mellitus. J Proteome Res 2015;14:512–20. 10.1021/pr500818d
    1. Poulsen KO, Sundekilde UK. The metabolomic analysis of human milk offers unique insights into potential child health benefits. Curr Nutr Rep 2021;10:12–29. 10.1007/s13668-020-00345-x
    1. Saben JL, Sims CR, Piccolo BD, et al. . Maternal adiposity alters the human milk metabolome: associations between nonglucose monosaccharides and infant adiposity. Am J Clin Nutr 2020;112:1228–39. 10.1093/ajcn/nqaa216
    1. Isganaitis E, Venditti S, Matthews TJ, et al. . Maternal obesity and the human milk metabolome: associations with infant body composition and postnatal weight gain. Am J Clin Nutr 2019;110:111–20. 10.1093/ajcn/nqy334
    1. Ninonuevo MR, Park Y, Yin H, et al. . A strategy for annotating the human milk glycome. J Agric Food Chem 2006;54:7471–80. 10.1021/jf0615810
    1. Bode L. The functional biology of human milk oligosaccharides. Early Hum Dev 2015;91:619–22. 10.1016/j.earlhumdev.2015.09.001
    1. LoCascio RG, Niñonuevo MR, Freeman SL, et al. . Glycoprofiling of bifidobacterial consumption of human milk oligosaccharides demonstrates strain specific, preferential consumption of small chain glycans secreted in early human lactation. J Agric Food Chem 2007;55:8914–9. 10.1021/jf0710480
    1. Sela DA. Bifidobacterial utilization of human milk oligosaccharides. Int J Food Microbiol 2011;149:58–64. 10.1016/j.ijfoodmicro.2011.01.025
    1. Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology 2012;22:1147–62. 10.1093/glycob/cws074
    1. Saben JL, Sims CR, Abraham A, et al. . Human milk oligosaccharide concentrations and infant intakes are associated with maternal overweight and obesity and predict infant growth. Nutrients 2021;13:446–16. 10.3390/nu13020446
    1. Gilley SP, Ruebel ML, Sims C, et al. . Associations between maternal obesity and offspring gut microbiome in the first year of life. Pediatr Obes 2022;17:e12921. 10.1111/ijpo.12921
    1. van Leeuwen SS. Challenges and pitfalls in human milk oligosaccharide analysis. Nutrients 2019;11:2684. 10.3390/nu11112684
    1. Newburg DS, Morelli L. Human milk and infant intestinal mucosal glycans guide succession of the neonatal intestinal microbiota. Pediatr Res 2015;77:115–20. 10.1038/pr.2014.178
    1. Boix-Amorós A, Collado MC, Mira A. Relationship between milk microbiota, bacterial load, macronutrients, and human cells during lactation. Front Microbiol 2016;7:492. 10.3389/fmicb.2016.00492
    1. Kordy K, Gaufin T, Mwangi M, et al. . Contributions to human breast milk microbiome and enteromammary transfer of Bifidobacterium breve. PLoS One 2020;15:e0219633–10. 10.1371/journal.pone.0219633
    1. Moore RE, Townsend SD. Temporal development of the infant gut microbiome. Open Biol 2019;9:190128. 10.1098/rsob.190128
    1. Sprenger N, Binia A, Austin S. Human milk oligosaccharides: factors affecting their composition and their physiological significance. Nestle Nutr Inst Workshop Ser 2019;90:43–56. 10.1159/000490292
    1. Gohir W, Ratcliffe EM, Sloboda DM. Of the bugs that shape us: maternal obesity, the gut microbiome, and long-term disease risk. Pediatr Res 2015;77:196–204. 10.1038/pr.2014.169
    1. Casado B, Affolter M, Kussmann M. OMICS-rooted studies of milk proteins, oligosaccharides and lipids. J Proteomics 2009;73:196–208. 10.1016/j.jprot.2009.09.018
    1. Rebollar EA, Antwis RE, Becker MH, et al. . Using "Omics" and Integrated Multi-Omics Approaches to Guide Probiotic Selection to Mitigate Chytridiomycosis and Other Emerging Infectious Diseases. Front Microbiol 2016;7:68. 10.3389/fmicb.2016.00068
    1. Bode L, Raman AS, Murch SH, et al. . Understanding the mother-breastmilk-infant “triad”. Science 2020;367:1070–2. 10.1126/science.aaw6147
    1. Lönnerdal B. Infant formula and infant nutrition: bioactive proteins of human milk and implications for composition of infant formulas. Am J Clin Nutr 2014;99:712S–7. 10.3945/ajcn.113.071993
    1. Lönnerdal B. Bioactive Proteins in Human Milk: Health, Nutrition, and Implications for Infant Formulas. J Pediatr 2016;173 Suppl:S4–9. 10.1016/j.jpeds.2016.02.070
    1. Kelishadi R, Farajian S. The protective effects of breastfeeding on chronic non-communicable diseases in adulthood: a review of evidence. Adv Biomed Res 2014;3:3:3. 10.4103/2277-9175.124629
    1. Isaacs EB, Morley R, Lucas A. Early diet and general cognitive outcome at adolescence in children born at or below 30 weeks gestation. J Pediatr 2009;155:229–34. 10.1016/j.jpeds.2009.02.030
    1. Victora CG, Bahl R, Barros AJD, et al. . Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet 2016;387:475–90. 10.1016/S0140-6736(15)01024-7
    1. Esch BCAMvan, Porbahaie M, Abbring S, et al. . The impact of milk and its components on epigenetic programming of immune function in early life and beyond: implications for allergy and asthma. Front Immunol 2020;11:2141. 10.3389/fimmu.2020.02141
    1. Chan A-W, Tetzlaff JM, Gøtzsche PC, et al. . Spirit 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:e7586. 10.1136/bmj.e7586
    1. Harris PA, Taylor R, Minor BL, et al. . The REDCap Consortium: building an international community of software platform partners. J Biomed Inform 2019;95:103208. 10.1016/j.jbi.2019.103208
    1. Harris PA, Taylor R, Thielke R, et al. . Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81. 10.1016/j.jbi.2008.08.010
    1. Carter M, Albar S, Morris M, et al. . Development of a UK online 24-h dietary assessment tool: myfood24. Nutrients 2015;7:4016–32. 10.3390/nu7064016
    1. Sundekilde UK, Downey E, O'Mahony JA, et al. . The effect of gestational and lactational age on the human milk metabolome. Nutrients 2016;8:304. 10.3390/nu8050304
    1. Hampel D, Shahab-Ferdows S, Hossain M, et al. . Validation and application of Biocrates AbsoluteIDQ® p180 targeted metabolomics kit using human milk. Nutrients 2019;11:1733. 10.3390/nu11081733
    1. Engholm-Keller K, Birck P, Størling J, et al. . TiSH — a robust and sensitive global phosphoproteomics strategy employing a combination of TiO2, SIMAC, and HILIC. J Proteomics 2012;75:5749–61. 10.1016/j.jprot.2012.08.007
    1. Brodkorb A, Egger L, Alminger M, et al. . INFOGEST static in vitro simulation of gastrointestinal food digestion. Nat Protoc 2019;14:991–1014. 10.1038/s41596-018-0119-1
    1. Nyamundanda G, Gormley IC, Fan Y, et al. . MetSizeR: selecting the optimal sample size for metabolomic studies using an analysis based approach. BMC Bioinformatics 2013;14:338. 10.1186/1471-2105-14-338
    1. Blaise BJ, Correia G, Tin A, et al. . Power analysis and sample size determination in metabolic phenotyping. Anal Chem 2016;88:5179–88. 10.1021/acs.analchem.6b00188
    1. Berger PK, Plows JF, Jones RB, et al. . Human milk oligosaccharide 2’-fucosyllactose links feedings at 1 month to cognitive development at 24 months in infants of normal and overweight mothers. PLoS One 2020;15:e0228323. 10.1371/journal.pone.0228323
    1. Samuel TM, Zhou Q, Giuffrida F, et al. . Nutritional and Non-nutritional composition of human milk is modulated by maternal, infant, and methodological factors. Front Nutr 2020;7:172. 10.3389/fnut.2020.576133
    1. Bzikowska-Jura A, Czerwonogrodzka-Senczyna A, Olędzka G, et al. . Maternal nutrition and body composition during breastfeeding: association with human milk composition. Nutrients 2018;10:1379. 10.3390/nu10101379
    1. Nommsen LA, Lovelady CA, Heinig MJ, et al. . Determinants of energy, protein, lipid, and lactose concentrations in human milk during the first 12 Mo of lactation: the Darling study. Am J Clin Nutr 1991;53:457–65. 10.1093/ajcn/53.2.457
    1. Kugananthan S, Gridneva Z, Lai C, et al. . Associations between maternal body composition and appetite hormones and macronutrients in human milk. Nutrients 2017;9:252. 10.3390/nu9030252

Source: PubMed

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