1
|
Al-Beltagi M. Human milk oligosaccharide secretion dynamics during breastfeeding and its antimicrobial role: A systematic review. World J Clin Pediatr 2025; 14. [DOI: 10.5409/wjcp.v14.i2.104797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 02/19/2025] [Accepted: 02/27/2025] [Indexed: 03/18/2025] Open
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.
Collapse
Affiliation(s)
- Mohammed Al-Beltagi
- Department of Paediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| |
Collapse
|
2
|
Sato K, Nakamura Y, Fujiyama K, Ohneda K, Nobukuni T, Ogishima S, Mizuno S, Koshiba S, Kuriyama S, Jinno S. Absolute quantification of eight human milk oligosaccharides in breast milk to evaluate their concentration profiles and associations with infants' neurodevelopmental outcomes. J Food Sci 2024; 89:10152-10170. [PMID: 39656795 DOI: 10.1111/1750-3841.17597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 11/03/2024] [Accepted: 11/21/2024] [Indexed: 12/17/2024]
Abstract
Human milk oligosaccharides (HMOs) have been positively associated with child neurodevelopment in some cohort studies. However, there is a lack of consistency in the association between HMOs and benefits to infants' brains. Moreover, the quantification methods for HMOs have not yet been standardized. In this study, we developed a quantification method for evaluating eight HMOs (2'-fucosyllactose [2'-FL], 3'-fucosyllactose [3'-FL], 3'-sialyllactose [3'-SL], 6'-sialyllactose [6'-SL], lactosialyltetrasaccharide a [LSTa], lactosialyltetrasaccharide b [LSTb], lactosialyltetrasaccharide c [LSTc], and disialyllacto-N-tetraose [DSLNT]) in breast milk. After validating the method, we applied it to 1-month breast milk samples (n = 150) from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study to assess HMO profiles in breast milk and their possible association with changes in head circumference z-score (ΔHCZ) and neurodevelopmental scores of children (as measured by the Ages and Stages Questionnaire, Third Edition). The validation demonstrated that the method had relative standard deviation ≤ 12.7% of precision and 79.5-110.9% of accuracy. Using this method, eight HMO levels (2'-FL, 0-4.74 mg/mL; 3'-FL, 0.02-1.52 mg/mL; 3'-SL, 0.07-0.32 mg/mL; 6'-SL, 0.01-0.70 mg/mL; LSTa, 0.002-0.043 mg/mL; LSTb, 0.02-0.31 mg/mL; LSTc, 0.001-0.47 mg/mL; and DSLNT, 0.09-0.71 mg/mL [min-max, all participants]) and the ratio of low secretors (16.0%) in the Japanese cohort were obtained. The obtained HMO levels in breast milk were subjected to multivariate analysis to screen for HMOs showing a positive association with ΔHCZ and neurodevelopmental scores. The results proposed that ΔHCZ was positively associated with LSTb and 2'-FL levels, whereas neurodevelopmental scores were positively associated with 2'-FL levels (among all participants) and 3'-SL and DSLNT levels (among secretor participants). This study showed that the developed method provides HMO profiles in Japanese breast milk, as well as additional information on the associations between specific HMOs and neurodevelopment, reinforcing the sum of evidence for the role of HMOs in the brain.
Collapse
Affiliation(s)
- Keigo Sato
- Food Microbiology and Function Research Laboratory, Meiji Co., Ltd., Hachioji, Japan
- Wellness Science Labs, Meiji Holdings Co., Ltd., Hachioji, Japan
- International Centre for Biotechnology, Osaka University, Suita, Japan
| | - Yoshitaka Nakamura
- Food Microbiology and Function Research Laboratory, Meiji Co., Ltd., Hachioji, Japan
| | - Kazuhito Fujiyama
- International Centre for Biotechnology, Osaka University, Suita, Japan
| | - Kinuko Ohneda
- Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
- Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Takahiro Nobukuni
- Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Soichi Ogishima
- Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
- Graduate School of Medicine, Tohoku University, Sendai, Japan
- Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai, Japan
| | - Satoshi Mizuno
- Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Seizo Koshiba
- Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
- Graduate School of Medicine, Tohoku University, Sendai, Japan
- Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai, Japan
| | - Shinichi Kuriyama
- Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
- Graduate School of Medicine, Tohoku University, Sendai, Japan
- International Research Institute of Disaster Science, Tohoku University, Sendai, Japan
| | - Shinji Jinno
- Food Microbiology and Function Research Laboratory, Meiji Co., Ltd., Hachioji, Japan
- Wellness Science Labs, Meiji Holdings Co., Ltd., Hachioji, Japan
| |
Collapse
|
3
|
Li LF, Shi X, Qi SM, Zhang XT, Fung HY, Li QR, Han QB. Strategies, techniques and applications for food authentication based on carbohydrates: A review. Carbohydr Polym 2024; 344:122533. [PMID: 39218564 DOI: 10.1016/j.carbpol.2024.122533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/09/2024] [Accepted: 07/21/2024] [Indexed: 09/04/2024]
Abstract
The increasing complexity and ubiquity of food processing and the emergence of fraudulent practices have made effective and reliable methods to authenticate food products of utmost importance. Carbohydrates, with various nutritional functions, are abundant in foods and can serve as potential markers for food authentication. However, the complex and diverse structures and properties of carbohydrates, especially polysaccharides, pose challenges. Nonetheless, significant progress has been made in this area. This paper provides an overview of the utilization of carbohydrates in food authentication since 2000, focusing on strategies involving carbohydrate-based markers, carbohydrate profiles, and carbohydrate-protein interaction-based assays. The analytical techniques, applications, challenges and limitations of these strategies are reviewed and discussed. The findings demonstrate that these strategies offer origin verification, quality assessment, adulteration detection, process control, and food species identification. Notably, oligosaccharide analysis has proven effective in food authentication and remains a promising marker, especially for analyzing intricate matrices. The advances in chromatography separation and mass spectrometry identification of isomers and trace amounts of these compounds have facilitated the discovery of such markers. In conclusion, carbohydrate analysis can play a crucial role in food authentication. Future research and development will make the authentication of carbohydrate-rich foods ever more accurate and efficient.
Collapse
Affiliation(s)
- Li-Feng Li
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Xi Shi
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Si-Min Qi
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Xue-Ting Zhang
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Hau-Yee Fung
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Qian-Ran Li
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Quan-Bin Han
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
| |
Collapse
|
4
|
Konieczna M, Koryszewska-Bagińska A, Bzikowska-Jura A, Chmielewska-Jeznach M, Jarzynka S, Olędzka G. Modifiable and Non-Modifiable Factors That Affect Human Milk Oligosaccharides Composition. Nutrients 2024; 16:2887. [PMID: 39275203 PMCID: PMC11397269 DOI: 10.3390/nu16172887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 08/22/2024] [Accepted: 08/27/2024] [Indexed: 09/16/2024] Open
Abstract
Human milk, the gold standard in infant nutrition, is a unique fluid that provides essential nutrients such as lactose, lipids, proteins, and free oligosaccharides. While its primary role is nutritional, it also protects against pathogens. This protection mainly comes from immunoglobulins, with human milk oligosaccharides (HMOs) providing additional support by inhibiting pathogen binding to host cell ligands. The prebiotic and immune-modulatory activity of HMOs strongly depends on their structure. Over 200 individual structures have been identified so far, with the composition varying significantly among women. The structure and composition of HMOs are influenced by factors such as the Lewis blood group, secretor status, and the duration of nursing. HMO profiles are heavily influenced by maternal phenotypes, which are defined based on the expression of two specific fucosyltransferases. However, recent data have shown that HMO content can be modified by various factors, both changeable and unchangeable, including diet, maternal age, gestational age, mode of delivery, breastfeeding frequency, and race. The first part of this overview presents the historical background of these sugars and the efforts by scientists to extract them using the latest chromatography methods. The second part is divided into subchapters that examine modifiable and non-modifiable factors, reviewing the most recent articles on HMO composition variations due to specific reasons and summarizing potential future challenges in conducting these types of studies.
Collapse
Affiliation(s)
- Małgorzata Konieczna
- Department of Medical Biology, Medical University of Warsaw, 00-575 Warsaw, Poland
| | | | - Agnieszka Bzikowska-Jura
- Department of Medical Biology, Medical University of Warsaw, 00-575 Warsaw, Poland
- Laboratory of Human Milk and Lactation Research, Department of Medical Biology, Medical University of Warsaw, 00-575 Warsaw, Poland
| | | | - Sylwia Jarzynka
- Department of Medical Biology, Medical University of Warsaw, 00-575 Warsaw, Poland
| | - Gabriela Olędzka
- Department of Medical Biology, Medical University of Warsaw, 00-575 Warsaw, Poland
| |
Collapse
|
5
|
Lordan C, Roche AK, Delsing D, Nauta A, Groeneveld A, MacSharry J, Cotter PD, van Sinderen D. Linking human milk oligosaccharide metabolism and early life gut microbiota: bifidobacteria and beyond. Microbiol Mol Biol Rev 2024; 88:e0009423. [PMID: 38206006 PMCID: PMC10966949 DOI: 10.1128/mmbr.00094-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024] Open
Abstract
SUMMARYHuman milk oligosaccharides (HMOs) are complex, multi-functional glycans present in human breast milk. They represent an intricate mix of heterogeneous structures which reach the infant intestine in an intact form as they resist gastrointestinal digestion. Therefore, they confer a multitude of benefits, directly and/or indirectly, to the developing neonate. Certain bifidobacterial species, being among the earliest gut colonizers of breast-fed infants, have an adapted functional capacity to metabolize various HMO structures. This ability is typically observed in infant-associated bifidobacteria, as opposed to bifidobacteria associated with a mature microbiota. In recent years, information has been gleaned regarding how these infant-associated bifidobacteria as well as certain other taxa are able to assimilate HMOs, including the mechanistic strategies enabling their acquisition and consumption. Additionally, complex metabolic interactions occur between microbes facilitated by HMOs, including the utilization of breakdown products released from HMO degradation. Interest in HMO-mediated changes in microbial composition and function has been the focal point of numerous studies, in recent times fueled by the availability of individual biosynthetic HMOs, some of which are now commonly included in infant formula. In this review, we outline the main HMO assimilatory and catabolic strategies employed by infant-associated bifidobacteria, discuss other taxa that exhibit breast milk glycan degradation capacity, and cover HMO-supported cross-feeding interactions and related metabolites that have been described thus far.
Collapse
Affiliation(s)
- Cathy Lordan
- Teagasc Food Research Centre, Fermoy, Co Cork, Ireland
| | - Aoife K. Roche
- APC Microbiome Ireland, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | | | - Arjen Nauta
- FrieslandCampina, Amersfoort, the Netherlands
| | | | - John MacSharry
- APC Microbiome Ireland, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Paul D. Cotter
- Teagasc Food Research Centre, Fermoy, Co Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Douwe van Sinderen
- APC Microbiome Ireland, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| |
Collapse
|