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

Johanne E Spreckels¹, Alexander Kurilshikov¹, Asier Fernández-Pato¹, Fan Liu², Siobhan Brushett³, Corinna Bang⁴, Daria V Zhernakova¹, Marloes Kruk¹, Trishla Sinha¹, Sanzhima Garmaeva¹, Milla F Brandao Gois¹, Esteban A Lopera-Maya¹, Laura A Bolte⁵, Soesma A Jankipersadsing¹, Andre Franke⁴, Hanne L P Tytgat⁶, Sara Colombo Mottaz⁷, Jingyuan Fu⁸; Lifelines NEXT cohort; Сyrus A Mallon¹, Sander S van Leeuwen⁹, Ranko Gacesa¹⁰, Alexandra Zhernakova¹¹

Affiliations

¹ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.
² Department of Pediatrics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; College of Food Science and Engineering, Shandong Agricultural University, Shandong 271018, China.
³ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; Department of Health Sciences, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.
⁴ Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein & Kiel University, 24105 Kiel, Germany.
⁵ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.
⁶ Nestlé Institute of Health Sciences, Nestlé Research, Société des Produits Nestlé S.A., 1000 Lausanne, Switzerland.
⁷ Nestlé Nutrition, Société des Produits Nestlé S.A., 1800 Vevey, Switzerland.
⁸ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; Department of Pediatrics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.
⁹ Department of Laboratory Medicine, University of Groningen and University Medical Center Groningen, Groningen 9713 GZ, the Netherlands; Van Hall Larenstein University of Applied Sciences, 8934 CJ. Leeuwarden, the Netherlands.
¹⁰ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands. Electronic address: r.gacesa@umcg.nl.
¹¹ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands. Electronic address: a.zhernakova@umcg.nl.

PMID: 40783943
DOI: 10.1016/j.celrep.2025.116124

Free article

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

Johanne E Spreckels et al. Cell Rep. 2025.

Free article

. 2025 Aug 26;44(8):116124.

doi: 10.1016/j.celrep.2025.116124. Epub 2025 Aug 8.

Authors

Affiliations

¹ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.
² Department of Pediatrics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; College of Food Science and Engineering, Shandong Agricultural University, Shandong 271018, China.
³ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; Department of Health Sciences, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.
⁴ Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein & Kiel University, 24105 Kiel, Germany.
⁵ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.
⁶ Nestlé Institute of Health Sciences, Nestlé Research, Société des Produits Nestlé S.A., 1000 Lausanne, Switzerland.
⁷ Nestlé Nutrition, Société des Produits Nestlé S.A., 1800 Vevey, Switzerland.
⁸ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; Department of Pediatrics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.
⁹ Department of Laboratory Medicine, University of Groningen and University Medical Center Groningen, Groningen 9713 GZ, the Netherlands; Van Hall Larenstein University of Applied Sciences, 8934 CJ. Leeuwarden, the Netherlands.
¹⁰ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands. Electronic address: r.gacesa@umcg.nl.
¹¹ Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands. Electronic address: a.zhernakova@umcg.nl.

PMID: 40783943
DOI: 10.1016/j.celrep.2025.116124

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: CP: Microbiology; bacterial sharing; breastfeeding; early life; genetics; gut microbiota; human milk microbiota; human milk oligosaccharide; infant feeding; infant health; longitudinal.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Miscellaneous