Lacto-N-tetraose, fucosylation, and secretor status are highly variable in human milk oligosaccharides from women delivering preterm

Maria Lorna A De Leoz, Stephanie C. Gaerlan, John S. Strum, Lauren M. Dimapasoc, Majid Mirmiran, Daniel J Tancredi, Jennifer T. Smilowitz, Karen M. Kalanetra, David A. Mills, J. Bruce German, Carlito B Lebrilla, Mark Underwood

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Breast milk is the ideal nutrition for term infants but must be supplemented to provide adequate growth for most premature infants. Human milk oligosaccharides (HMOs) are remarkably abundant and diverse in breast milk and yet provide no nutritive value to the infant. HMOs appear to have at least two major functions: prebiotic activity (stimulation of the growth of commensal bacteria in the gut) and protection against pathogens. Investigations of HMOs in milk from women delivering preterm have been limited. We present the first detailed mass spectrometric analysis of the fucosylation and sialylation in HMOs in serial specimens of milk from 15 women delivering preterm and 7 women delivering at term using nanohigh performance liquid chromatography chip/time-of-flight mass spectrometry. A mixed-effects model with Levene's test was used for the statistical analyses. We find that lacto-N-tetraose, a core HMO, is both more abundant and more highly variable in the milk of women delivering preterm. Furthermore, fucosylation in preterm milk is not as well regulated as in term milk, resulting in higher within and between mother variation in women delivering preterm vs term. Of particular clinical interest, the α1,2-linked fucosylated oligosaccharide 2′-fucosyllactose, an indicator of secretor status, is not consistently present across lactation of several mothers that delivered preterm. The immaturity of HMO production does not appear to resolve over the time of lactation and may have relevance to the susceptibility of premature infants to necrotizing enterocolitis, late onset sepsis, and related neurodevelopmental impairments.

Original languageEnglish (US)
Pages (from-to)4662-4672
Number of pages11
JournalJournal of Proteome Research
Volume11
Issue number9
DOIs
StatePublished - Sep 7 2012

Fingerprint

Human Milk
Oligosaccharides
Milk
Lactation
Premature Infants
Mothers
Prebiotics
Necrotizing Enterocolitis
lacto-N-neotetraose
Liquid chromatography
Nutritive Value
Pathogens
Nutrition
Growth
Liquid Chromatography
Mass spectrometry
Mass Spectrometry
Sepsis
Bacteria

Keywords

  • fucosyllactose
  • HMO
  • LNT
  • mass spectrometry
  • premature infant
  • sialic acid
  • sialylation

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Lacto-N-tetraose, fucosylation, and secretor status are highly variable in human milk oligosaccharides from women delivering preterm. / De Leoz, Maria Lorna A; Gaerlan, Stephanie C.; Strum, John S.; Dimapasoc, Lauren M.; Mirmiran, Majid; Tancredi, Daniel J; Smilowitz, Jennifer T.; Kalanetra, Karen M.; Mills, David A.; German, J. Bruce; Lebrilla, Carlito B; Underwood, Mark.

In: Journal of Proteome Research, Vol. 11, No. 9, 07.09.2012, p. 4662-4672.

Research output: Contribution to journalArticle

De Leoz, MLA, Gaerlan, SC, Strum, JS, Dimapasoc, LM, Mirmiran, M, Tancredi, DJ, Smilowitz, JT, Kalanetra, KM, Mills, DA, German, JB, Lebrilla, CB & Underwood, M 2012, 'Lacto-N-tetraose, fucosylation, and secretor status are highly variable in human milk oligosaccharides from women delivering preterm', Journal of Proteome Research, vol. 11, no. 9, pp. 4662-4672. https://doi.org/10.1021/pr3004979
De Leoz, Maria Lorna A ; Gaerlan, Stephanie C. ; Strum, John S. ; Dimapasoc, Lauren M. ; Mirmiran, Majid ; Tancredi, Daniel J ; Smilowitz, Jennifer T. ; Kalanetra, Karen M. ; Mills, David A. ; German, J. Bruce ; Lebrilla, Carlito B ; Underwood, Mark. / Lacto-N-tetraose, fucosylation, and secretor status are highly variable in human milk oligosaccharides from women delivering preterm. In: Journal of Proteome Research. 2012 ; Vol. 11, No. 9. pp. 4662-4672.
@article{87b9318d4cb849c0a2c43f238f314a22,
title = "Lacto-N-tetraose, fucosylation, and secretor status are highly variable in human milk oligosaccharides from women delivering preterm",
abstract = "Breast milk is the ideal nutrition for term infants but must be supplemented to provide adequate growth for most premature infants. Human milk oligosaccharides (HMOs) are remarkably abundant and diverse in breast milk and yet provide no nutritive value to the infant. HMOs appear to have at least two major functions: prebiotic activity (stimulation of the growth of commensal bacteria in the gut) and protection against pathogens. Investigations of HMOs in milk from women delivering preterm have been limited. We present the first detailed mass spectrometric analysis of the fucosylation and sialylation in HMOs in serial specimens of milk from 15 women delivering preterm and 7 women delivering at term using nanohigh performance liquid chromatography chip/time-of-flight mass spectrometry. A mixed-effects model with Levene's test was used for the statistical analyses. We find that lacto-N-tetraose, a core HMO, is both more abundant and more highly variable in the milk of women delivering preterm. Furthermore, fucosylation in preterm milk is not as well regulated as in term milk, resulting in higher within and between mother variation in women delivering preterm vs term. Of particular clinical interest, the α1,2-linked fucosylated oligosaccharide 2′-fucosyllactose, an indicator of secretor status, is not consistently present across lactation of several mothers that delivered preterm. The immaturity of HMO production does not appear to resolve over the time of lactation and may have relevance to the susceptibility of premature infants to necrotizing enterocolitis, late onset sepsis, and related neurodevelopmental impairments.",
keywords = "fucosyllactose, HMO, LNT, mass spectrometry, premature infant, sialic acid, sialylation",
author = "{De Leoz}, {Maria Lorna A} and Gaerlan, {Stephanie C.} and Strum, {John S.} and Dimapasoc, {Lauren M.} and Majid Mirmiran and Tancredi, {Daniel J} and Smilowitz, {Jennifer T.} and Kalanetra, {Karen M.} and Mills, {David A.} and German, {J. Bruce} and Lebrilla, {Carlito B} and Mark Underwood",
year = "2012",
month = "9",
day = "7",
doi = "10.1021/pr3004979",
language = "English (US)",
volume = "11",
pages = "4662--4672",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
number = "9",

}

TY - JOUR

T1 - Lacto-N-tetraose, fucosylation, and secretor status are highly variable in human milk oligosaccharides from women delivering preterm

AU - De Leoz, Maria Lorna A

AU - Gaerlan, Stephanie C.

AU - Strum, John S.

AU - Dimapasoc, Lauren M.

AU - Mirmiran, Majid

AU - Tancredi, Daniel J

AU - Smilowitz, Jennifer T.

AU - Kalanetra, Karen M.

AU - Mills, David A.

AU - German, J. Bruce

AU - Lebrilla, Carlito B

AU - Underwood, Mark

PY - 2012/9/7

Y1 - 2012/9/7

N2 - Breast milk is the ideal nutrition for term infants but must be supplemented to provide adequate growth for most premature infants. Human milk oligosaccharides (HMOs) are remarkably abundant and diverse in breast milk and yet provide no nutritive value to the infant. HMOs appear to have at least two major functions: prebiotic activity (stimulation of the growth of commensal bacteria in the gut) and protection against pathogens. Investigations of HMOs in milk from women delivering preterm have been limited. We present the first detailed mass spectrometric analysis of the fucosylation and sialylation in HMOs in serial specimens of milk from 15 women delivering preterm and 7 women delivering at term using nanohigh performance liquid chromatography chip/time-of-flight mass spectrometry. A mixed-effects model with Levene's test was used for the statistical analyses. We find that lacto-N-tetraose, a core HMO, is both more abundant and more highly variable in the milk of women delivering preterm. Furthermore, fucosylation in preterm milk is not as well regulated as in term milk, resulting in higher within and between mother variation in women delivering preterm vs term. Of particular clinical interest, the α1,2-linked fucosylated oligosaccharide 2′-fucosyllactose, an indicator of secretor status, is not consistently present across lactation of several mothers that delivered preterm. The immaturity of HMO production does not appear to resolve over the time of lactation and may have relevance to the susceptibility of premature infants to necrotizing enterocolitis, late onset sepsis, and related neurodevelopmental impairments.

AB - Breast milk is the ideal nutrition for term infants but must be supplemented to provide adequate growth for most premature infants. Human milk oligosaccharides (HMOs) are remarkably abundant and diverse in breast milk and yet provide no nutritive value to the infant. HMOs appear to have at least two major functions: prebiotic activity (stimulation of the growth of commensal bacteria in the gut) and protection against pathogens. Investigations of HMOs in milk from women delivering preterm have been limited. We present the first detailed mass spectrometric analysis of the fucosylation and sialylation in HMOs in serial specimens of milk from 15 women delivering preterm and 7 women delivering at term using nanohigh performance liquid chromatography chip/time-of-flight mass spectrometry. A mixed-effects model with Levene's test was used for the statistical analyses. We find that lacto-N-tetraose, a core HMO, is both more abundant and more highly variable in the milk of women delivering preterm. Furthermore, fucosylation in preterm milk is not as well regulated as in term milk, resulting in higher within and between mother variation in women delivering preterm vs term. Of particular clinical interest, the α1,2-linked fucosylated oligosaccharide 2′-fucosyllactose, an indicator of secretor status, is not consistently present across lactation of several mothers that delivered preterm. The immaturity of HMO production does not appear to resolve over the time of lactation and may have relevance to the susceptibility of premature infants to necrotizing enterocolitis, late onset sepsis, and related neurodevelopmental impairments.

KW - fucosyllactose

KW - HMO

KW - LNT

KW - mass spectrometry

KW - premature infant

KW - sialic acid

KW - sialylation

UR - http://www.scopus.com/inward/record.url?scp=84866060251&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866060251&partnerID=8YFLogxK

U2 - 10.1021/pr3004979

DO - 10.1021/pr3004979

M3 - Article

C2 - 22900748

AN - SCOPUS:84866060251

VL - 11

SP - 4662

EP - 4672

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 9

ER -