Systematic Reviews
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Pediatr. Jun 9, 2025; 14(2): 104797
Published online Jun 9, 2025. doi: 10.5409/wjcp.v14.i2.104797
Human milk oligosaccharide secretion dynamics during breastfeeding and its antimicrobial role: A systematic review
Mohammed Al-Beltagi
Mohammed Al-Beltagi, Department of Paediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
Mohammed Al-Beltagi, Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
Author contributions: Al-Beltagi M is the sole author of this study; Al-Beltagi M conceptualized the research, conducted the systematic literature search, performed data extraction and analysis, and interpreted the findings; Al-Beltagi M also drafted the manuscript, addressed reviewer comments, and finalized the revisions; Al-Beltagi M approved the final version of the manuscript for submission.
Conflict-of-interest statement: The author declares no conflict of interest.
PRISMA 2009 Checklist statement: This systematic review was conducted in accordance with the PRISMA 2009 guidelines. The study followed a structured approach, including a comprehensive literature search, predefined inclusion and exclusion criteria, systematic data extraction, and risk of bias assessment. A PRISMA flow diagram was used to illustrate the study selection process.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mohammed Al-Beltagi, MD, PhD, Chief Physician, Professor, Department of Paediatrics, Faculty of Medicine, Tanta University, 1 Hassan Radwan Street, Tanta 31511, Alghrabia, Egypt. mbelrem@hotmail.com
Received: January 2, 2025
Revised: February 19, 2025
Accepted: February 27, 2025
Published online: June 9, 2025
Processing time: 75 Days and 20.1 Hours
Abstract
BACKGROUND

Human milk oligosaccharides (HMOs) are bioactive components of breast milk with diverse health benefits, including shaping the gut microbiota, modulating the immune system, and protecting against infections. HMOs exhibit dynamic secretion patterns during lactation, influenced by maternal genetics and environmental factors. Their direct and indirect antimicrobial properties have garnered significant research interest. However, a comprehensive understanding of the secretion dynamics of HMOs and their correlation with antimicrobial efficacy remains underexplored.

AIM

To synthesize current evidence on the secretion dynamics of HMOs during lactation and evaluate their antimicrobial roles against bacterial, viral, and protozoal pathogens.

METHODS

A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library focused on studies investigating natural and synthetic HMOs, their secretion dynamics, and antimicrobial properties. Studies involving human, animal, and in vitro models were included. Data on HMO composition, temporal secretion patterns, and mechanisms of antimicrobial action were extracted. Quality assessment was performed using validated tools appropriate for study design.

RESULTS

A total of 44 studies were included, encompassing human, animal, and in vitro research. HMOs exhibited dynamic secretion patterns, with 2′-fucosyllactose (2′-FL) and lacto-N-tetraose peaking in early lactation and declining over time, while 3-fucosyllactose (3-FL) increased during later stages. HMOs demonstrated significant antimicrobial properties through pathogen adhesion inhibition, biofilm disruption, and enzymatic activity impairment. Synthetic HMOs, including bioengineered 2′-FL and 3-FL, were structurally and functionally comparable to natural HMOs, effectively inhibiting pathogens such as Pseudomonas aeruginosa, Escherichia coli, and Campylobacter jejuni. Additionally, HMOs exhibited synergistic effects with antibiotics, enhancing their efficacy against resistant pathogens.

CONCLUSION

HMOs are vital in antimicrobial defense, supporting infant health by targeting various pathogens. Both natural and synthetic HMOs hold significant potential for therapeutic applications, particularly in infant nutrition and as adjuncts to antibiotics. Further research, including clinical trials, is essential to address gaps in knowledge, validate findings, and explore the broader applicability of HMOs in improving maternal and neonatal health.

Keywords: Human milk oligosaccharides; Human milk oligosaccharides secretion dynamics; Antimicrobial activity; Breastfeeding; Synthetic human milk oligosaccharides; Pathogen adhesion inhibition; Infant health

Core Tip: This systematic review highlights human milk oligosaccharides (HMOs)' dynamic secretion patterns and antimicrobial properties (HMOs), emphasizing their crucial role in infant health. HMOs protect against many pathogens by inhibiting adhesion, disrupting biofilms, and impairing bacterial enzymatic activity. Synthetic HMOs, including 2′-fucosyllactose and 3-fucosyllactose, replicate the structure and function of natural HMOs, offering scalable solutions for therapeutic applications. HMOs also synergize with antibiotics, enhancing their efficacy and addressing antimicrobial resistance. These findings underscore HMOs' potential to develop innovative maternal and neonatal care interventions, improving global health outcomes.