Host and environmental determinants of human milk oligosaccharides and microbiota in the 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
Affiliations
Johanne E. Spreckels
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Alexander Kurilshikov
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Asier Fernández-Pato
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Fan Liu
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
Siobhan Brushett
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
Corinna Bang
Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein & Kiel University, 24105 Kiel, Germany
Daria V. Zhernakova
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Marloes Kruk
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Trishla Sinha
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Sanzhima Garmaeva
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Milla F. Brandao Gois
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Esteban A. Lopera-Maya
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Laura A. Bolte
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
Soesma A. Jankipersadsing
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Andre Franke
Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein & Kiel University, 24105 Kiel, Germany
Hanne L.P. Tytgat
Nestlé Institute of Health Sciences, Nestlé Research, Société des Produits Nestlé S.A., 1000 Lausanne, Switzerland
Sara Colombo Mottaz
Nestlé Nutrition, Société des Produits Nestlé S.A., 1800 Vevey, Switzerland
Jingyuan Fu
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
Сyrus A. Mallon
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
Sander S. van Leeuwen
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
Ranko Gacesa
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; Corresponding author
Alexandra Zhernakova
Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, the Netherlands; Corresponding author
Summary: 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.
