Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children

Amirthagowri Ambalavanan; Le Chang; Jihoon Choi; Yang Zhang; Sara A Stickley; Zhi Y Fang; Kozeta Miliku; Bianca Robertson; Chloe Yonemitsu; Stuart E Turvey; Piushkumar J Mandhane; Elinor Simons; Theo J Moraes; Sonia S Anand; Guillaume Paré; Janet E Williams; Brenda M Murdoch; Gloria E Otoo; Samwel Mbugua; Elizabeth W Kamau-Mbuthia; Egidioh W Kamundia; Debela K Gindola; Juan M Rodriguez; Rossina G Pareja; Daniel W Sellen; Sophie E Moore; Andrew M Prentice; James A Foster; Linda J Kvist; Holly L Neibergs; Mark A McGuire; Michelle K McGuire; Courtney L Meehan; Malcolm R Sears; Padmaja Subbarao; Meghan B Azad; Lars Bode; Qingling Duan

doi:10.1038/s41467-024-51743-6

Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children

Nat Commun. 2024 Sep 4;15(1):7735. doi: 10.1038/s41467-024-51743-6.

Authors

Amirthagowri Ambalavanan¹, Le Chang^{1

2}, Jihoon Choi¹, Yang Zhang², Sara A Stickley¹, Zhi Y Fang¹, Kozeta Miliku^{3

4}, Bianca Robertson⁵, Chloe Yonemitsu⁵, Stuart E Turvey⁶, Piushkumar J Mandhane^{7

8}, Elinor Simons⁹, Theo J Moraes¹⁰, Sonia S Anand¹¹, Guillaume Paré¹², Janet E Williams¹³, Brenda M Murdoch¹³, Gloria E Otoo¹⁴, Samwel Mbugua¹⁵, Elizabeth W Kamau-Mbuthia¹⁵, Egidioh W Kamundia¹⁵, Debela K Gindola¹⁶, Juan M Rodriguez¹⁷, Rossina G Pareja¹⁸, Daniel W Sellen¹⁹, Sophie E Moore^{20

21}, Andrew M Prentice²¹, James A Foster²², Linda J Kvist²³, Holly L Neibergs²⁴, Mark A McGuire¹³, Michelle K McGuire²⁵, Courtney L Meehan²⁶, Malcolm R Sears³, Padmaja Subbarao^{3

10}, Meghan B Azad^{27

28}, Lars Bode²⁹, Qingling Duan^{30

31}

Affiliations

¹ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
² School of Computing, Queen's University, Kingston, ON, Canada.
³ Department of Medicine, McMaster University, Hamilton, ON, Canada.
⁴ Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
⁵ Department of Pediatrics and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), Human Milk Institute (HMI), University of California San Diego, La Jolla, CA, USA.
⁶ Department of Pediatrics, Division of Allergy and Immunology, University of British Columbia, Vancouver, BC, Canada.
⁷ Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
⁸ Faculty of Medicine, USCI University, Kuala Lumpur, Malaysia.
⁹ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
¹⁰ Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
¹¹ Chanchlani Research Centre, Dept. of Medicine, McMaster University, Hamilton, ON, Canada.
¹² Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
¹³ Department of Animal, Veterinary and Food Sciences, University of Idaho, Moscow, Idaho, USA.
¹⁴ Department of Nutrition & Food Science, University of Ghana, Accra, Ghana.
¹⁵ Department of Human Nutrition, Egerton University, Nakuru, Kenya.
¹⁶ Department of Anthropology, Hawassa University, Hawassa, Ethiopia.
¹⁷ Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain.
¹⁸ Nutrition Research Institute, Lima, Peru.
¹⁹ Department of Anthropology, University of Toronto, Toronto, ON, Canada.
²⁰ Department of Women and Children's Health, King's College London, London, UK.
²¹ The Medical Research Council Unit, The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, Gambia.
²² Department of Biological Sciences, University of Idaho, Moscow, ID, USA.
²³ Faculty of Medicine, Lund University, Lund, Sweden.
²⁴ Department of Animal Sciences, Washington State University, Pullman, WA, USA.
²⁵ Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID, USA.
²⁶ Department of Anthropology, Washington State University, Pullman, WA, USA.
²⁷ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada. [email protected].
²⁸ Manitoba Interdisciplinary Lactation Centre (MILC), Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. [email protected].
²⁹ Department of Pediatrics and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), Human Milk Institute (HMI), University of California San Diego, La Jolla, CA, USA. [email protected].
³⁰ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada. [email protected].
³¹ School of Computing, Queen's University, Kingston, ON, Canada. [email protected].

Abstract

Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e-118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6'-sialyllactose (P = 2.2e-9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P < 0.01). Thus, we report novel genetic factors associated with HMOs, some of which may protect the respiratory health of children.

MeSH terms

Adult
Breast Feeding
Child
Child, Preschool
Chromosomes, Human, Pair 3 / genetics
Cohort Studies
Female
Fucosyltransferases / genetics
Gene-Environment Interaction
Genome-Wide Association Study*
Humans
Infant
Lactose / analogs & derivatives
Male
Milk, Human* / chemistry
Milk, Human* / metabolism
Mothers
Oligosaccharides* / metabolism
Polymorphism, Single Nucleotide
Respiratory Sounds / genetics
Sialyltransferases* / genetics
Sialyltransferases* / metabolism

Substances

Oligosaccharides
Sialyltransferases
Fucosyltransferases
6'-sialyllactose
Lactose

Abstract

MeSH terms

Substances

Grants and funding