Human milk oligosaccharides: Maternal determinants and effects on infant gut microbiome, and infant cognitive and behavioral development during early life

Human milk (HM) is the recommended feeding method for infants by various global health organizations. According to the World Health Organization, in 2024, 48% of infants under 6 months worldwide were exclusively breastfed. HM provides all required nutrients as well as numerous bioactive compounds to infants during critical windows of postnatal development. HM is also considered unique for its high oligosaccharide content. Human milk oligosaccharides (HMOs) are resistant to infant digestive enzymes and can work as prebiotics to exert beneficial effects to infants. HMO profiles differ by individual mothers. One of the biggest drivers for HMO composition is maternal secretor status, where secretor mothers have an active 2-fucosyltransferase (FUT2) gene and the capacity to produce α1,2-fucosylated HMOs. This dissertation utilized biological and questionnaire data collected from a longitudinal birth cohort study, Synergistic Theory and Research on Nutrition and Obesity Group (STRONG) kids 2 (SKP2). The SKP2 cohort recruited from the central Illinois area had an initial cohort of 468 mothers in their third trimester of pregnancy. HM samples were collected at 6 weeks postpartum; Demographic data were collected via self-reported questionnaires, and infant stool samples were collected by research staff during home visits at various timepoints in the first four years of life. Analyses suggested that maternal genetics, body weight status, pregnancy complications, and dietary characteristics were associated with HMO composition. Given the variations in HMO compositions, infants get different HMO profile exposures, thus, we explored infant outcomes related to HMO exposure. HMO composition was significantly associated with infant behavioral outcomes, including temperament traits and eating behaviors, from infancy to 4-year-old. Additionally, associations were found between HMO composition and infant microbiota composition, including microbiota alpha- and beta-diversity and individual genus-level relative abundances. Lastly, we explored the potential for characteristics of the microbiota composition (diversity and taxa) as a mediator between HMO and infant temperament traits and eating behaviors. However, we only found the positive association between DFS-LNH and enjoyment of food at 12 months being mediated by microbiota alpha diversity at 12 months. In summary, the findings in this research demonstrated that the HMO composition of human breast milk is affected by various maternal factors, including genetics, weight status and dietary intake. Exposure to different HMOs is associated with neurocognitive and behavioral development in infants and children, with infant microbiome being the potential mediating factor. The present study highlighted the vital role of HMO in early development, encouraging further investigation and targeted interventions to optimize infant nutrition.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Food Science & Human Nutrition

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Fan, Yuting (Grace)

Contributors dc:contributor

• Donovan, Sharon M
• Miller, Michael
• Khan, Naiman A
• Bost, Kelly F

• Human milk oligosaccharide
• Infant behavioral development
• Maternal diet
• Infant Microbiome development

Statement dc:rights

• Copyright 2025 Yuting (Grace) Fan

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/129757

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F129757