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Observational Study
. 2017 May;105(5):1086-1100.
doi: 10.3945/ajcn.116.139980. Epub 2017 Mar 29.

What's normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically

Michelle K McGuire  1   2 , Courtney L Meehan  3 , Mark A McGuire  4 , Janet E Williams  4   5 , James Foster  6 , Daniel W Sellen  7 , Elizabeth W Kamau-Mbuthia  8 , Egidioh W Kamundia  8 , Samwel Mbugua  8 , Sophie E Moore  9   10 , Andrew M Prentice  11 , Linda J Kvist  12 , Gloria E Otoo  13 , Sarah L Brooker  4   5 , William J Price  14 , Bahman Shafii  14 , Caitlyn Placek  3 , Kimberly A Lackey  15 , Bianca Robertson  16   17 , Susana Manzano  18 , Lorena Ruíz  18 , Juan M Rodríguez  18 , Rossina G Pareja  19 , Lars Bode  20   17
Affiliations
Observational Study

What's normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically

Michelle K McGuire et al. Am J Clin Nutr. 2017 May.

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.

Keywords: breastfeeding; carbohydrates; human milk; lactation; oligosaccharides.

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Figures

FIGURE 1
FIGURE 1
Mean ± SEM absolute total and HMO isoform concentrations of all women combined (A), nonsecretors (B), and secretors (C). (A and B) Bars without a common lowercase letter represent total HMO values that differed with the use of Bonferroni-correction procedures for multiple comparisons. All statistical inferences were carried out on log-transformed data. Note that there was only one nonsecretor subject each in Peru and United States - CA. CA, California; DFLac, difucosyllactose; DFLNH, difucosyllacto-N-hexaose; DFLNT, difucosyllacto-N-tetrose; DSLNH, disialyllacto-N-hexaose; DSLNT, disialyllacto-N-tetraose; FDSLNH, fucodisialyllacto-N-hexaose; FLNH, fucosyllacto-N-hexaose; HMO, human milk oligosaccharide; LNFP, lacto-N-fucopentaose; LNH, lacto-N-hexaose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetrose; LSTb, sialyl-lacto-N-tetraose b; LSTc, sialyl-lacto-N-tetraose c; WA, Washington; 2′FL, 2′-fucosyllactose; 3FL, 3-fucosyllactose; 3′SL, 3′-sialyllactose; 6′SL, 6′-sialyllactose.
FIGURE 2
FIGURE 2
Mean ± SEM relative abundance of HMO concentrations of all women combined (A), nonsecretors (B), and secretors (C) in each cohort. Note that there was only one nonsecretor subject each in Peru and United States - CA. CA, California; DFLac, difucosyllactose; DFLNH, difucosyllacto-N-hexaose; DFLNT, difucosyllacto-N-tetrose; DSLNH, disialyllacto-N-hexaose; DSLNT, disialyllacto-N-tetraose; FDSLNH, fucodisialyllacto-N-hexaose; FLNH, fucosyllacto-N-hexaose; HMO, human milk oligosaccharide; LNFP, lacto-N-fucopentaose; LNH, lacto-N-hexaose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetrose; LSTb, sialyl-lacto-N-tetraose b; LSTc, sialyl-lacto-N-tetraose c; WA, Washington; 2′FL, 2′-fucosyllactose; 3FL, 3-fucosyllactose; 3′SL, 3′-sialyllactose; 6′SL, 6′-sialyllactose.
FIGURE 3
FIGURE 3
Percentages of women in each cohort categorized as secretors. Cohorts that do not share a common lowercase letter differ (P < 0.05) in terms of their percentages of women who were secretors with the use of a chi-square test with Benjamini and Hochberg false-discovery-rate corrections. ETR, rural Ethiopia; ETU, urban Ethiopia; GBR, rural Gambia; GBU, urban Gambia; GN, Ghana; KE, Kenya; PE, Peru; SP, Spain; SW, Sweden; USC, United States–California (Hispanic); USW, United States–Washington.
FIGURE 4
FIGURE 4
Spearman rank correlations between selected maternal anthropometric, demographic, and reproductive variables and HMO types and groupings. Sizes of dots and colors indicate directionality (blue denotes positive; red denotes negative) and the strength of the association. Total HMO-bound sialic acid; total HMO-bound fucose; small HMO; type 1; type 2; α-1,2; α-1,3; and α-2,6 were calculated as: the sum of all sialic acid moieties bound to each HMO; all fucose moieties bound to each HMO; 2′FL + 3FL + 3′SL + 6′SL; LNT + LNFPI + LNFPII + LSTb + DSLNT; LNnT + LNFPIII + LSTc; LNFP I + 2′FL; LNFP III + 3FL; and LSTb + LSTc + 6′SL, respectively. DFLac, difucosyllactose; DFLNH, difucosyllacto-N-hexaose; DFLNT, difucosyllacto-N-tetrose; DSLNH, disialyllacto-N-hexaose; DSLNT, disialyllacto-N-tetraose; FDSLNH, fucodisialyllacto-N-hexaose; FLNH, fucosyllacto-N-hexaose; HMO, human milk oligosaccharide; LNFP, lacto-N-fucopentaose; LNH, lacto-N-hexaose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetrose; LST, sialyl-lacto-N-tetraose; 2′FL, 2′-fucosyllactose; 3FL, 3-fucosyllactose; 3′SL, 3′-sialyllactose; 6′SL, 6′-sialyllactose.
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References

    1. Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology 2012;22:1147–62. - PMC - PubMed
    1. Coppa GV, Pierani P, Zampini L, Carloni I, Carlucci A, Gabrielli O. Oligosaccharides in human milk during different phases of lactation. Acta Paediatr Suppl 1999;88:89–94. - PubMed
    1. Kunz C, Rodriguez-Palmero M, Koletzko B, Jensen R. Nutritional and biochemical properties of human milk, part I: general aspects, proteins, and carbohydrates. Clin Perinatol 1999;26:307–33. - PubMed
    1. Newburg DS, Shen Z, Warren CD. Quantitative analysis of human milk oligosaccharides by capillary electrophoresis. Adv Exp Med Biol 2000;478:381–2. - PubMed
    1. Chaturvedi P, Warren CD, Altaye M, Morrow AL, Ruiz-Palacios G, Pickering LK, Newburg DS. Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. Glycobiology 2001;11:365–72. - PubMed

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