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. 2025 Nov 20;17(22):3622.
doi: 10.3390/nu17223622.

Development of the Breastfed Infant Oral Microbiome Is Associated with Concentrations and Intakes of Human Milk Oligosaccharides

Roaa A Arishi  1   2   3   4 , Ali S Cheema  5 , Jacki L McEachran  1   2   3 , Zoya Gridneva  1   2   3 , Annalee Furst  6 , Ana Roman  6 , Lars Bode  6 , Ching Tat Lai  1   2   3 , Matthew S Payne  7 , Donna T Geddes  1   2   3 , Lisa F Stinson  1   2   3
Affiliations

Development of the Breastfed Infant Oral Microbiome Is Associated with Concentrations and Intakes of Human Milk Oligosaccharides

Roaa A Arishi et al. Nutrients. .

Abstract

Background/Objectives: Human milk oligosaccharides (HMOs) are bioactive carbohydrates abundant in human milk that shape the infant gut microbiome, yet their influence on the oral microbiome remains poorly understood. This study investigated associations between HMO concentrations and infant HMO intakes and the composition of the oral microbiome in predominantly (n = 2) and exclusively (n = 54) breastfed infants. Methods: We profiled infant oral samples collected at 2 months of age using full-length 16S rRNA gene sequencing, alongside paired milk HMO analyses from 56 mother-infant dyads from the Western Australian BLOSOM cohort. Daily HMO intakes were calculated using 24 h milk intake data. Results: Concentrations of human milk 3FL and LNFPIII were negatively associated with infant oral Shannon diversity (p = 0.027) and richness (p = 0.037), respectively. LNFPII concentration and daily intake were linked to increased abundance of Neisseria subflava (both p = 0.025), while daily intakes of DFLNT and DFLNH were positively associated with Streptococcus parasanguinis (p = 0.028 and p = 0.040). Notably, the associations observed for daily HMO intakes were modest in effect size. Conclusions: These findings demonstrate a statistically significant but biologically limited effect of HMOs on the development of the infant oral microbiome. By clarifying how specific components of human milk shape early microbial development, this work provides mechanistic insights relevant to nutritional and supportive interventions that promote breastfeeding success.

Keywords: breastfeeding; human milk; human milk oligosaccharides; infant oral microbiome.

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Conflict of interest statement

D.T.G. declares participation in the Scientific Advisory Board of Medela AG. C.T.L., L.F.S., J.L.M., Z.G. and D.T.G. are/were supported by an unrestricted research grant from Medela AG, administered by The University of Western Australia. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Conceptual diagram illustrating the hypothesised mechanisms through which HMOs may influence the infant oral microbial ecology. Purple boxes represent local effects driven by the concentration of HMOs in milk, while yellow boxes represent systemic effects driven by total intake of HMOs. Created in BioRender: https://BioRender.com/6901bjv (accessed on 9 November 2025).
Figure 2
Figure 2
Infant oral and human milk HMO profiles across the cohort. Individuals are plotted on the x-axis, with microbiome and HMO data aligned vertically for each individual. (A), Relative abundances of the 15 most abundant operational taxonomic units (OTUs) in infant oral samples, stratified by maternal secretor status. (B), HMO concentrations in individual mothers based on secretor status. HMO, human milk oligosaccharides.
Figure 3
Figure 3
Associations between HMO concentration and the infant oral microbiome. Lines represent linear model fits, and shaded areas show 95% confidence intervals. HMO, human milk oligosaccharides.
Figure 4
Figure 4
Associations between HMO intakes and infant oral taxa. Lines represent linear model fits, and shaded areas show 95% confidence intervals. HMO, human milk oligosaccharides.
See this image and copyright information in PMC

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