Host and environmental determinants of human milk oligosaccharides and microbiota in the Lifelines NEXT cohort

Lifelines NEXT cohort; Johanne E Spreckels; Alexander Kurilshikov; Asier Fernández-Pato; Fan Liu; Siobhan Brushett; Corinna Bang; Daria V Zhernakova; Marloes Kruk; Trishla Sinha; Sanzhima Garmaeva; Milla F Brandao Gois; Esteban A Lopera-Maya; Laura A Bolte; Soesma A Jankipersadsing; Andre Franke; Hanne L P Tytgat; Sara Colombo Mottaz; Jingyuan Fu; Сyrus A Mallon; Sander S van Leeuwen; Ranko Gacesa; Alexandra Zhernakova

doi:10.1016/j.celrep.2025.116124

Host and environmental determinants of human milk oligosaccharides and microbiota in the Lifelines NEXT cohort

Lifelines NEXT cohort, Johanne E Spreckels, Alexander Kurilshikov, Asier Fernández-Pato, Fan Liu, Siobhan Brushett, Corinna Bang, Daria V Zhernakova, Marloes Kruk, Trishla Sinha, Sanzhima Garmaeva, Milla F Brandao Gois, Esteban A Lopera-Maya, Laura A Bolte, Soesma A Jankipersadsing, Andre Franke, Hanne L P Tytgat, Sara Colombo Mottaz, Jingyuan Fu, Сyrus A MallonSander S van Leeuwen, Ranko Gacesa^*, Alexandra Zhernakova^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Human milk is important for infant development, but few large studies have comprehensively investigated milk composition. Here, we characterized human milk oligosaccharides (HMOs) and milk microbiota, their shaping factors, and their links to infant gut microbiota in the longitudinal Dutch Lifelines NEXT cohort. We measured 24 HMOs in 1,542 milk samples from 524 mothers at 0.5-6 months postpartum, profiled microbiota in milk and maternal and infant feces, genotyped mothers, and recorded 174 environmental, maternal, and infant characteristics. HMO concentrations were associated with maternal genetic loci (FUT2, FUT3/FUT6, ABO, and ST3GAL6), lactation stage, and subclinical mastitis. The human milk microbiota varied during lactation and with different feeding practices. Both HMOs and milk microbiota remained stable across multiple pregnancies in the same individual. Some milk bacteria were present in infant feces, but the milk and infant fecal microbiota diverged as the infant aged. Furthermore, individual HMOs were associated with infant fecal microbiota characteristics.

Original language	English
Article number	116124
Number of pages	30
Journal	Cell reports
Volume	44
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2025.116124
Publication status	Published - 26-Aug-2025

Keywords

Humans
Milk, Human/metabolism
Oligosaccharides/metabolism
Female
Infant
Feces/microbiology
Gastrointestinal Microbiome
Adult
Cohort Studies
Microbiota
Lactation
Infant, Newborn
Breast Feeding
Pregnancy

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Host and environmental determinants of human milk oligosaccharides and microbiota in the Lifelines NEXT cohortFinal publisher's version, 14.1 MBLicence: CC BY

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Lifelines NEXT cohort, Spreckels, J. E., Kurilshikov, A., Fernández-Pato, A., Liu, F., Brushett, S., Bang, C., Zhernakova, D. V., Kruk, M., Sinha, T., Garmaeva, S., Brandao Gois, M. F., Lopera-Maya, E. A., Bolte, L. A., Jankipersadsing, S. A., Franke, A., Tytgat, H. L. P., Mottaz, S. C., Fu, J., ... Zhernakova, A. (2025). Host and environmental determinants of human milk oligosaccharides and microbiota in the Lifelines NEXT cohort. Cell reports, 44(8), Article 116124. https://doi.org/10.1016/j.celrep.2025.116124

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title = "Host and environmental determinants of human milk oligosaccharides and microbiota in the Lifelines NEXT cohort",

abstract = "Human milk is important for infant development, but few large studies have comprehensively investigated milk composition. Here, we characterized human milk oligosaccharides (HMOs) and milk microbiota, their shaping factors, and their links to infant gut microbiota in the longitudinal Dutch Lifelines NEXT cohort. We measured 24 HMOs in 1,542 milk samples from 524 mothers at 0.5-6 months postpartum, profiled microbiota in milk and maternal and infant feces, genotyped mothers, and recorded 174 environmental, maternal, and infant characteristics. HMO concentrations were associated with maternal genetic loci (FUT2, FUT3/FUT6, ABO, and ST3GAL6), lactation stage, and subclinical mastitis. The human milk microbiota varied during lactation and with different feeding practices. Both HMOs and milk microbiota remained stable across multiple pregnancies in the same individual. Some milk bacteria were present in infant feces, but the milk and infant fecal microbiota diverged as the infant aged. Furthermore, individual HMOs were associated with infant fecal microbiota characteristics.",

keywords = "Humans, Milk, Human/metabolism, Oligosaccharides/metabolism, Female, Infant, Feces/microbiology, Gastrointestinal Microbiome, Adult, Cohort Studies, Microbiota, Lactation, Infant, Newborn, Breast Feeding, Pregnancy",

author = "\{Lifelines NEXT cohort\} and Spreckels, \{Johanne E\} and Alexander Kurilshikov and Asier Fern{\'a}ndez-Pato and Fan Liu and Siobhan Brushett and Corinna Bang and Zhernakova, \{Daria V\} and Marloes Kruk and Trishla Sinha and Sanzhima Garmaeva and \{Brandao Gois\}, \{Milla F\} and Lopera-Maya, \{Esteban A\} and Bolte, \{Laura A\} and Jankipersadsing, \{Soesma A\} and Andre Franke and Tytgat, \{Hanne L P\} and Mottaz, \{Sara Colombo\} and Jingyuan Fu and Mallon, \{Сyrus A\} and \{van Leeuwen\}, \{Sander S\} and Ranko Gacesa and Alexandra Zhernakova",

year = "2025",

month = aug,

day = "26",

doi = "10.1016/j.celrep.2025.116124",

language = "English",

volume = "44",

journal = "Cell reports",

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Lifelines NEXT cohort, Spreckels, JE , Kurilshikov, A , Fernández-Pato, A, Liu, F, Brushett, S, Bang, C, Zhernakova, DV, Kruk, M , Sinha, T , Garmaeva, S , Brandao Gois, MF, Lopera-Maya, EA, Bolte, LA , Jankipersadsing, SA, Franke, A, Tytgat, HLP, Mottaz, SC, Fu, J , Mallon, СA, van Leeuwen, SS, Gacesa, R & Zhernakova, A 2025, 'Host and environmental determinants of human milk oligosaccharides and microbiota in the Lifelines NEXT cohort', Cell reports, vol. 44, no. 8, 116124. https://doi.org/10.1016/j.celrep.2025.116124

TY - JOUR

T1 - Host and environmental determinants of human milk oligosaccharides and microbiota in the Lifelines NEXT cohort

AU - Lifelines NEXT cohort

AU - Spreckels, Johanne E

AU - Kurilshikov, Alexander

AU - Fernández-Pato, Asier

AU - Liu, Fan

AU - Brushett, Siobhan

AU - Bang, Corinna

AU - Zhernakova, Daria V

AU - Kruk, Marloes

AU - Sinha, Trishla

AU - Garmaeva, Sanzhima

AU - Brandao Gois, Milla F

AU - Lopera-Maya, Esteban A

AU - Bolte, Laura A

AU - Jankipersadsing, Soesma A

AU - Franke, Andre

AU - Tytgat, Hanne L P

AU - Mottaz, Sara Colombo

AU - Fu, Jingyuan

AU - Mallon, Сyrus A

AU - van Leeuwen, Sander S

AU - Gacesa, Ranko

AU - Zhernakova, Alexandra

PY - 2025/8/26

Y1 - 2025/8/26

N2 - Human milk is important for infant development, but few large studies have comprehensively investigated milk composition. Here, we characterized human milk oligosaccharides (HMOs) and milk microbiota, their shaping factors, and their links to infant gut microbiota in the longitudinal Dutch Lifelines NEXT cohort. We measured 24 HMOs in 1,542 milk samples from 524 mothers at 0.5-6 months postpartum, profiled microbiota in milk and maternal and infant feces, genotyped mothers, and recorded 174 environmental, maternal, and infant characteristics. HMO concentrations were associated with maternal genetic loci (FUT2, FUT3/FUT6, ABO, and ST3GAL6), lactation stage, and subclinical mastitis. The human milk microbiota varied during lactation and with different feeding practices. Both HMOs and milk microbiota remained stable across multiple pregnancies in the same individual. Some milk bacteria were present in infant feces, but the milk and infant fecal microbiota diverged as the infant aged. Furthermore, individual HMOs were associated with infant fecal microbiota characteristics.

AB - Human milk is important for infant development, but few large studies have comprehensively investigated milk composition. Here, we characterized human milk oligosaccharides (HMOs) and milk microbiota, their shaping factors, and their links to infant gut microbiota in the longitudinal Dutch Lifelines NEXT cohort. We measured 24 HMOs in 1,542 milk samples from 524 mothers at 0.5-6 months postpartum, profiled microbiota in milk and maternal and infant feces, genotyped mothers, and recorded 174 environmental, maternal, and infant characteristics. HMO concentrations were associated with maternal genetic loci (FUT2, FUT3/FUT6, ABO, and ST3GAL6), lactation stage, and subclinical mastitis. The human milk microbiota varied during lactation and with different feeding practices. Both HMOs and milk microbiota remained stable across multiple pregnancies in the same individual. Some milk bacteria were present in infant feces, but the milk and infant fecal microbiota diverged as the infant aged. Furthermore, individual HMOs were associated with infant fecal microbiota characteristics.

KW - Humans

KW - Milk, Human/metabolism

KW - Oligosaccharides/metabolism

KW - Female

KW - Infant

KW - Feces/microbiology

KW - Gastrointestinal Microbiome

KW - Adult

KW - Cohort Studies

KW - Microbiota

KW - Lactation

KW - Infant, Newborn

KW - Breast Feeding

KW - Pregnancy

U2 - 10.1016/j.celrep.2025.116124

DO - 10.1016/j.celrep.2025.116124

M3 - Article

C2 - 40783943

SN - 2211-1247

VL - 44

JO - Cell reports

JF - Cell reports

IS - 8

M1 - 116124

ER -

Host and environmental determinants of human milk oligosaccharides and microbiota in the Lifelines NEXT cohort

Abstract

Keywords

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