title: What's normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically.
abstract: Background:Human milk is a complex fluid comprised of myriad substances, with one of the most abundant substances being a group of complex carbohydrates referred to as human milk oligosaccharides (HMOs). There has been some evidence that HMO profiles differ in populations, but few studies have rigorously explored this variability.Objectives:We tested the hypothesis that HMO profiles differ in diverse populations of healthy women. Next, we examined relations between HMO and maternal anthropometric and reproductive indexes and indirectly examined whether differences were likely related to genetic or environmental variations.Design:In this cross-sectional, observational study, milk was collected from a total of 410 healthy, breastfeeding women in 11 international cohorts and analyzed for HMOs by using high-performance liquid chromatography.Results:There was an effect of the cohort (P< 0.05) on concentrations of almost all HMOs. For instance, the mean 3-fucosyllactose concentration was >4 times higher in milk collected in Sweden than in milk collected in rural Gambia (mean ± SEM: 473 ± 55 compared with 103 ± 16 nmol/mL, respectively;P< 0.05), and disialyllacto-N-tetraose (DSLNT) concentrations ranged from 216 ± 14 nmol/mL (in Sweden) to 870 ± 68 nmol/mL (in rural Gambia) (P< 0.05). Maternal age, time postpartum, weight, and body mass index were all correlated with several HMOs, and multiple differences in HMOs [e.g., lacto-N-neotetrose and DSLNT] were shown between ethnically similar (and likely genetically similar) populations who were living in different locations, which suggests that the environment may play a role in regulating the synthesis of HMOs.Conclusions:The results of this study support our hypothesis that normal HMO concentrations and profiles vary geographically, even in healthy women. Targeted genomic analyses are required to determine whether these differences are due at least in part to genetic variation. A careful examination of sociocultural, behavioral, and environmental factors is needed to determine their roles in this regard. This study was registered at clinicaltrials.gov as NCT02670278.
authors.affiliation: School of Biological Sciences, smcguire@wsu.edu lbode@ucsd.edu.|Paul G Allen School for Global Animal Health, and.
authors.forename: Michelle K
authors.identifier: 0000-0001-8214-2229
authors.initials: MK
authors.lastname: McGuire
authors.affiliation: Department of Anthropology, Washington State University, Pullman, WA.
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Meehan
authors.affiliation: Department of Animal and Veterinary Science.
authors.forename: Mark A
authors.initials: MA
authors.lastname: McGuire
authors.affiliation: Department of Animal and Veterinary Science.|Program in Bioinformatics and Computational Biology.
authors.forename: Janet E
authors.identifier: 0000-0002-9769-1789
authors.initials: JE
authors.lastname: Williams
authors.affiliation: Department of Biological Sciences, and.
authors.forename: James
authors.initials: J
authors.lastname: Foster
authors.affiliation: Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Sellen
authors.affiliation: Department of Human Nutrition, Egerton University, Nakuru, Kenya.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Kamau-Mbuthia
authors.affiliation: Department of Human Nutrition, Egerton University, Nakuru, Kenya.
authors.forename: Egidioh W
authors.initials: EW
authors.lastname: Kamundia
authors.affiliation: Department of Human Nutrition, Egerton University, Nakuru, Kenya.
authors.forename: Samwel
authors.initials: S
authors.lastname: Mbugua
authors.affiliation: Medical Research Council (MRC), Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.|MRC Unit, Banjul, The Gambia.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Moore
authors.affiliation: MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
authors.affiliation: Faculty of Medicine, Lund University, Lund, Sweden.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Kvist
authors.affiliation: Department of Nutrition and Food Science, University of Ghana, Accra, Ghana.
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Otoo
authors.affiliation: Department of Animal and Veterinary Science.|Program in Bioinformatics and Computational Biology.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Brooker
authors.affiliation: Statistical Programs, College of Agricultural and Life Sciences, University of Idaho, Moscow, ID.
authors.forename: William J
authors.initials: WJ
authors.lastname: Price
authors.affiliation: Statistical Programs, College of Agricultural and Life Sciences, University of Idaho, Moscow, ID.
authors.forename: Bahman
authors.initials: B
authors.lastname: Shafii
authors.affiliation: Department of Anthropology, Washington State University, Pullman, WA.
authors.forename: Caitlyn
authors.initials: C
authors.lastname: Placek
authors.affiliation: School of Biological Sciences.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Lackey
authors.affiliation: Department of Pediatrics and.|Mother Milk Infant Center of Research Excellence, University of California, San Diego, La Jolla, CA.
authors.forename: Bianca
authors.initials: B
authors.lastname: Robertson
authors.affiliation: Department of Nutrition, Food Science, and Food Technology, Complutense University of Madrid, Madrid, Spain; and.
authors.forename: Susana
authors.identifier: 0000-0002-0925-538X
authors.initials: S
authors.lastname: Manzano
authors.affiliation: Department of Nutrition, Food Science, and Food Technology, Complutense University of Madrid, Madrid, Spain; and.
authors.forename: Lorena
authors.initials: L
authors.lastname: Ruíz
authors.affiliation: Department of Nutrition, Food Science, and Food Technology, Complutense University of Madrid, Madrid, Spain; and.
authors.forename: Juan M
authors.identifier: 0000-0002-1285-9686
authors.initials: JM
authors.lastname: Rodríguez
authors.affiliation: Nutrition Research Institute, Lima, Peru.
authors.forename: Rossina G
authors.initials: RG
authors.lastname: Pareja
authors.affiliation: Department of Pediatrics and smcguire@wsu.edu lbode@ucsd.edu.|Mother Milk Infant Center of Research Excellence, University of California, San Diego, La Jolla, CA.
authors.forename: Lars
authors.initials: L
authors.lastname: Bode
mesh_terms: D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D001835:Body Weight; D001942:Breast Feeding; D003430:Cross-Sectional Studies; D004777:Environment; D005006:Ethnicity; D005260:Female; D005714:Gambia; D059647:Gene-Environment Interaction; D006801:Humans; D007774:Lactation / Q000378:metabolism*; D008895:Milk, Human / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism*; D049590:Postpartum Period; D012016:Reference Values; D013548:Sweden; D055815:Young Adult
chemical_list: D009844:Oligosaccharides; C576246:disialyllacto-N-tetraose; C035714:3'-fucosyllactose
keywords: breastfeeding; carbohydrates; human milk; lactation; oligosaccharides