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Al-Beltagi M. Human milk oligosaccharide secretion dynamics during breastfeeding and its antimicrobial role: A systematic review. World J Clin Pediatr 2025; 14:104797. [DOI: 10.5409/wjcp.v14.i2.104797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [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.
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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
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Hou H, Wang M, Yang S, Yang X, Sun W, Sun X, Guo Q, Debrah AA, Zhenxia D. Evaluation of Prebiotic Glycan Composition in Human Milk and Infant Formula: Profile of Galacto-Oligosaccharides and Absolute Quantification of Major Milk Oligosaccharides by UPLC-Cyclic IM-MS and UPLC-MS/MS. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:7980-7990. [PMID: 38562102 DOI: 10.1021/acs.jafc.4c00810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
Prebiotic oligosaccharides have attracted immense interest in the infant formula (IF) industry due to their unique health benefits for infants. There is a need for the reasonable supplementation of prebiotics in premium IF products. Herein, we characterized the profile of galacto-oligosaccharides (GOS) in human milk (HM) and IF using ultrahigh-performance liquid chromatography-cyclic ion mobility-mass spectrometry (UPLC-cIM-MS) technique. Additionally, we further performed a targeted quantitative analysis of five essential HM oligosaccharides (HMOs) in HM (n = 196), IF (n = 50), and raw milk of IF (n = 10) by the high-sensitivity UPLC-MS/MS method. HM exhibited a more abundant and variable HMO composition (1183.19 to 2892.91 mg/L) than IF (32.91 to 56.31 mg/L), whereas IF contained extra GOS species and non-negligible endogenous 3'-sialyllactose. This also facilitated the discovery of secretor features within the Chinese population. Our study illustrated the real disparity in the prebiotic glycome between HM and IF and provided crucial reference for formula improvement.
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Affiliation(s)
- Haiyue Hou
- College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China
| | - Mengyu Wang
- College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China
| | - Shuya Yang
- College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China
| | - Xuexin Yang
- Waters Technology (Beijing) Co., Ltd., Jinghai Industrial Park, 156 Jinghai 4th Road, Beijing Economic-Technological Development Area, Beijing 100076, China
| | - Wenjun Sun
- Waters Technology (Beijing) Co., Ltd., Jinghai Industrial Park, 156 Jinghai 4th Road, Beijing Economic-Technological Development Area, Beijing 100076, China
| | - Xuechun Sun
- College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China
| | - Qiaozhen Guo
- Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing 100013, China
| | - Augustine Atta Debrah
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
| | - Du Zhenxia
- College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China
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Sun A, Tian L, Xiong X, Kuchan M, Dai X, Sun H, Wang H, Li X, Zhang L, Zhao Y, Chen J, Mao Y, Li X. Carotenoids in maternal and cord blood, breast milk and their association with maternal dietary intake: a longitudinal study in Shanghai, China. Br J Nutr 2024; 131:1041-1052. [PMID: 37926900 DOI: 10.1017/s000711452300257x] [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: 11/07/2023]
Abstract
Carotenoids are important bioactive substances in breast milk, the profile of which is seldom studied. This study aimed to explore the profile of carotenoids in breast milk and maternal/cord plasma of healthy mother-neonate pairs in Shanghai, China, and their correlation with dietary intake. Maternal blood, umbilical cord blood and breast milk samples from five lactation stages (colostrum, transitional milk and early-, mid- and late-term mature milk) were collected. Carotenoid levels were analysed by HPLC. Carotenoid levels in breast milk changed as lactation progressed (P < 0·001). β-Carotene was the primary carotenoid in colostrum. Lutein accounted for approximately 50 % of total carotenoids in transitional milk, mature milk and cord blood. Positive correlations were observed between five carotenoids in umbilical cord blood and maternal blood (P all < 0·001). β-Carotene levels were also correlated between maternal plasma and three stages of breast milk (r = 0·605, P < 0·001; r = 0·456, P = 0·011, r = 0·446; P = 0·013, respectively). Dietary carotenoid intakes of lactating mothers also differed across lactation stages, although no correlation with breast milk concentrations was found. These findings suggest the importance of exploring the transport mechanism of carotenoids between mothers and infants and help guide the development of formulas for Chinese infants as well as the nutritional diets of lactating mothers.
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Affiliation(s)
- Anran Sun
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu610041, People's Republic of China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu610041, People's Republic of China
| | - Luojia Tian
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu610041, People's Republic of China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu610041, People's Republic of China
| | - Xiaoying Xiong
- Abbott Nutrition Research & Development Centre, Shanghai200233, People's Republic of China
| | - Matthew Kuchan
- Abbott Nutrition Research & Development Center, Abbott Laboratories, Columbus, OH43219, USA
| | - Xinyao Dai
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu610041, People's Republic of China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu610041, People's Republic of China
| | - Hanxiao Sun
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu610041, People's Republic of China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu610041, People's Republic of China
| | - He Wang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu610041, People's Republic of China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu610041, People's Republic of China
| | - Xiang Li
- Abbott Nutrition Research & Development Centre, Shanghai200233, People's Republic of China
| | - Lishi Zhang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu610041, People's Republic of China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu610041, People's Republic of China
| | - Yanrong Zhao
- Abbott Nutrition Research & Development Centre, Shanghai200233, People's Republic of China
| | - Jinyao Chen
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu610041, People's Republic of China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu610041, People's Republic of China
| | - Yingyi Mao
- Abbott Nutrition Research & Development Centre, Shanghai200233, People's Republic of China
| | - Xiaomeng Li
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu610041, People's Republic of China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu610041, People's Republic of China
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Sun W, Tao L, Qian C, Xue P, Tong X, Yang L, Lu F, Wan H, Tao Y. Human milk oligosaccharides and the association with microbiota in colostrum: a pilot study. Arch Microbiol 2024; 206:58. [PMID: 38191870 PMCID: PMC10774193 DOI: 10.1007/s00203-023-03787-3] [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: 10/19/2023] [Revised: 10/25/2023] [Accepted: 12/04/2023] [Indexed: 01/10/2024]
Abstract
HMOs (Human milk oligosaccharide) has an impact on maternal and infant health. Colostrum samples of 70 breastfeeding women in China were collected and recorded clinical characteristics. The major oligosaccharides and microbiota were quantitated in colostrum. The concentration of fucosylated HMOs in primipara was higher than that of multipara (p = 0.030). The concentration of N-acetylated HMOs in vaginal delivery milk was less than that of cesarean (p = 0.038). Non-fucosylated HMOs of breastfeeding women were less than that of breast pump (p = 0.038). Meanwhile, the concentration of LNT was positively correlated with Lactobacillus (r = 0.250, p = 0.037). DS-LNT was negatively correlated with Staphylococcus (r = - 0.240, p = 0.045). There was a positive correlation of Streptococcus with LNFP II (r = 0.314, p = 0.011) and 3-SL (r = 0.322, p = 0.009). In addition, there was a negative correlation between 2'-FL and 3-FL (r = - 0.465, p = 0.001). There was a positive correlation between LNT and LNnT (r = 0.778, p = 0.001). Therefore, the concentration of HMOs is related to number of deliveries, delivery mode, lactation mode and perinatal antibiotic. The concentration of HMOs is related to Lactobacillus, Streptococcus and Streptococcus in colostrum. In addition, there are connections between different oligosaccharides in content. The study protocol was also registered in the ClinicalTrails.gov (ChiCTR2200064454) (Oct. 2022).
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Affiliation(s)
- Wen Sun
- Department of Traditional Chinese Medicine, Shanghai Fourth People's Hospital Affiliated to Tongji University, Shanghai, 200434, China
| | - Lin Tao
- Department of Traditional Chinese Medicine, Shanghai Fourth People's Hospital Affiliated to Tongji University, Shanghai, 200434, China
| | - Chen Qian
- Department of Traditional Chinese Medicine, Shanghai Fourth People's Hospital Affiliated to Tongji University, Shanghai, 200434, China
| | - Peipei Xue
- Department of Traditional Chinese Medicine, Shanghai Fourth People's Hospital Affiliated to Tongji University, Shanghai, 200434, China
| | - Xiankun Tong
- Laboratory of Immunopharmacology, Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Li Yang
- Laboratory of Immunopharmacology, Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Fang Lu
- Department of Gynaecology and Obstetrics, Shanghai Fourth People's Hospital Affiliated to Tongji University, Shanghai, 200434, China
| | - Hua Wan
- Department of Breast, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Yingna Tao
- Department of Traditional Chinese Medicine, Shanghai Fourth People's Hospital Affiliated to Tongji University, Shanghai, 200434, China.
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Liu S, Mao Y, Wang J, Tian F, Hill DR, Xiong X, Li X, Zhao Y, Wang S. Lactational and geographical variation in the concentration of six oligosaccharides in Chinese breast milk: a multicenter study over 13 months postpartum. Front Nutr 2023; 10:1267287. [PMID: 37731395 PMCID: PMC10508235 DOI: 10.3389/fnut.2023.1267287] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 08/23/2023] [Indexed: 09/22/2023] Open
Abstract
Introduction Understanding the variations of oligosaccharide in breast milk contribute to better study how human milk oligosaccharides (HMOs) play a role in health-promoting benefits in infants. Methods Six abundant HMOs, 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), Lacto-N-tetraose (LNT), Lacto-N-neotetraose (LNnT), 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL), in breast milk collected at 0-5 days, 10-15 days, 40-45 days, 200-240 days, and 300-400 days postpartum from six locations across China were analyzed using high-performance anion-exchange chromatography-pulsed amperometric detector. Results The concentration of individual HMO fluctuated dynamically during lactational stages. The median ranges of 2'-FL, 3-FL, LNT, LNnT, 3'-SL, and 6'-SL across the five lactational stages were 935-2865 mg/L, 206-1325 mg/L, 300-1473 mg/L, 32-317 mg/L, 106-228 mg/L, and 20-616 mg/L, respectively. The prominent variation was observed in the content of 6'-SL, which demonstrates a pattern of initial increase followed by a subsequent decrease. Among the five lactational stages, the transitional milk has the highest concentration, which was 31 times greater than the concentration in mature milk at 300-400 days postpartum, where the content is the lowest. Geographical location also influenced the content of HMOs. LNT and LNnT were the highest in mature milk of mothers from Lanzhou among the six sites at 40-240 days postpartum. Breast milks were categorized into two groups base on the abundance of 2'-FL (high and low). There was no significant difference in the proportions of high and low 2'-FL phenotypes among the six sites, and the percentages of high and low 2'-FL phenotypes were 79% and 21%, respectively, across all sites in China. Discussion This study provided a comprehensive dataset on 6 HMOs concentrations in Chinese breast milk during the extended postpartum period across a wide geographic range and stratified by high and low 2'-FL phenotypes.
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Affiliation(s)
- Shuang Liu
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, China
| | - Yingyi Mao
- Abbott Nutrition Research & Development Center, Shanghai, China
| | - Jin Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, China
| | - Fang Tian
- Abbott Nutrition Research & Development Center, Shanghai, China
| | - David R. Hill
- Abbott Nutrition Research & Development Center, Columbus, OH, United States
| | - Xiaoying Xiong
- Abbott Nutrition Research & Development Center, Shanghai, China
| | - Xiang Li
- Abbott Nutrition Research & Development Center, Shanghai, China
| | - Yanrong Zhao
- Abbott Nutrition Research & Development Center, Shanghai, China
| | - Shuo Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, China
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Abstract
Human milk oligosaccharides (HMOs) are the third most important solid component in human milk and act in tandem with other bioactive components. Individual HMO levels and distribution vary greatly between mothers by multiple variables, such as secretor status, race, geographic region, environmental conditions, season, maternal diet, and weight, gestational age and mode of delivery. HMOs improve the gastrointestinal barrier and also promote a bifidobacterium-rich gut microbiome, which protects against infection, strengthens the epithelial barrier, and creates immunomodulatory metabolites. HMOs fulfil a variety of physiologic functions including potential support to the immune system, brain development, and cognitive function. Supplementing infant formula with HMOs is safe and promotes a healthy development of the infant revealing benefits for microbiota composition and infection prevention. Because of limited data comparing the effect of non-human oligosaccharides to HMOs, it is not known if HMOs offer an additional clinical benefit over non-human oligosaccharides. Better knowledge of the factors influencing HMO composition and their functions will help to understand their short- and long-term benefits.
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Affiliation(s)
- Meltem Dinleyici
- Department of Social Pediatrics, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | - Jana Barbieur
- UZ Brussel, KidZ Health Castle, Vrije Unversiteit Brussel, Brussels, Belgium
| | - Ener Cagri Dinleyici
- Department of Pediatrics, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey
| | - Yvan Vandenplas
- UZ Brussel, KidZ Health Castle, Vrije Unversiteit Brussel, Brussels, Belgium
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Vitamins, Vegetables and Metal Elements Are Positively Associated with Breast Milk Oligosaccharide Composition among Mothers in Tianjin, China. Nutrients 2022; 14:nu14194131. [PMID: 36235783 PMCID: PMC9570563 DOI: 10.3390/nu14194131] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 09/30/2022] [Accepted: 10/02/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Human milk oligosaccharides (HMOs) are a group of breast milk carbohydrates exerting pivotal benefits for breastfed infants. Whether maternal diet is associated with breastmilk HMO composition has not been well-characterized. OBJECTIVES We investigated the associations between dietary nutrient intake and HMO concentrations in a general pregnant and postpartum population. METHODS A total of 383 breast milk samples and the corresponding food frequency questionnaires during 0-400 postpartum days from 277 mothers were collected. Six different HMOs were detected in mothers' milk. The correlation between nutrients and HMOs were analyzed using a linear mixed-effects model. RESULTS We found plant nutrients, vitamin A, vitamin C and vegetables as positive predictors of 3-fucosyllactose; vitamin B1 and vitamin B2 were positive predictors for 2'-fucosyllactose level and the sum of 2'-fucosyllactose and 3-fucosyllactose; tocopherol and metal elements were positive predictors for 3'-sialyllactose; and metal elements were positively associated with the sum of all the six HMOs; the milk and lactose intake was a positive predictor of lacto-N-tetraose levels and the sum of lacto-N-tetraose and lacto-N-neotetraose. CONCLUSIONS The results show that vegetables, vitamins and metal elements are dietary components positively associated with HMO concentrations.
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Wang J, Chen MS, Wang RS, Hu JQ, Liu S, Wang YYF, Xing XL, Zhang BW, Liu JM, Wang S. Current Advances in Structure-Function Relationships and Dose-Dependent Effects of Human Milk Oligosaccharides. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:6328-6353. [PMID: 35593935 DOI: 10.1021/acs.jafc.2c01365] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
HMOs (human milk oligosaccharides) are the third most important nutrient in breast milk. As complex glycans, HMOs play an important role in regulating neonatal intestinal immunity, resisting viral and bacterial infections, displaying anti-inflammatory characteristics, and promoting brain development. Although there have been some previous reports of HMOs, a detailed literature review summarizing the structure-activity relationships and dose-dependent effects of HMOs is lacking. Hence, after introducing the structures and synthetic pathways of HMOs, this review summarizes and categorizes identified structure-function relationships of HMOs. Differential mechanisms of different structural HMOs utilization by microorganisms are summarized. This review also emphasizes the recent advances in the interactions between different health benefits and the variance of dosage effect based on in vitro cell tests, animal experiments, and human intervention studies. The potential relationships between the chemical structure, the dosage selection, and the physiological properties of HMOs as functional foods are vital for further understanding of HMOs and their future applications.
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Affiliation(s)
- Jin Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin 300071, China
| | - Meng-Shan Chen
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin 300071, China
| | - Rui-Shan Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin 300071, China
| | - Jia-Qiang Hu
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin 300071, China
| | - Shuang Liu
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin 300071, China
| | - Yuan-Yi-Fei Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin 300071, China
| | - Xiao-Long Xing
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin 300071, China
| | - Bo-Wei Zhang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin 300071, China
| | - Jing-Min Liu
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin 300071, China
| | - Shuo Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin 300071, China
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Gold MS, Quinn PJ, Campbell DE, Peake J, Smart J, Robinson M, O’Sullivan M, Vogt JK, Pedersen HK, Liu X, Pazirandeh-Micol E, Heine RG. Effects of an Amino Acid-Based Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety, and Gut Microbiome in Infants with Cow's Milk Protein Allergy. Nutrients 2022; 14:nu14112297. [PMID: 35684099 PMCID: PMC9182596 DOI: 10.3390/nu14112297] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 05/26/2022] [Accepted: 05/27/2022] [Indexed: 12/04/2022] Open
Abstract
This open-label, non-randomized, multicenter trial (Registration: NCT03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow's milk protein allergy (CMPA). Term infants aged 1-8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from -0.31 at the baseline to +0.28 at the 4-months' follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.
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Affiliation(s)
- Michael S. Gold
- Department of Allergy & Immunology, Women’s and Children’s Hospital, University of Adelaide, Adelaide, SA 5006, Australia;
- Correspondence:
| | - Patrick J. Quinn
- Department of Allergy & Immunology, Women’s and Children’s Hospital, University of Adelaide, Adelaide, SA 5006, Australia;
| | - Dianne E. Campbell
- Department of Allergy & Clinical Immunology, Children’s Hospital at Westmead, University of Sydney, Sydney, NSW 2145, Australia;
| | - Jane Peake
- Queensland Paediatric Immunology and Allergy Service, Queensland Children’s Hospital, University of Queensland, South Brisbane, QLD 4101, Australia;
| | - Joanne Smart
- Paediatric Allergy Services, Epworth Hospital, Richmond, VIC 3121, Australia;
| | - Marnie Robinson
- Melbourne Allergy Centre & Children’s Specialists Medical Group, Parkville, VIC 3152, Australia;
| | - Michael O’Sullivan
- Department of Immunology, Perth Children’s Hospital, Nedlands, WA 6009, Australia
| | | | | | - Xiaoqiu Liu
- Biostatistics and Data Science Division, The George Institute for Global Health, University of New South Wales, Sydney, NSW 2042, Australia;
| | | | - Ralf G. Heine
- Nestlé Health Science, CH-1800 Vevey, Switzerland; (E.P.-M.); (R.G.H.)
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Vandenplas Y, Żołnowska M, Berni Canani R, Ludman S, Tengelyi Z, Moreno-Álvarez A, Goh AEN, Gosoniu ML, Kirwan BA, Tadi M, Heine RG. Effects of an Extensively Hydrolyzed Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety and Infection Risk in Infants with Cow's Milk Protein Allergy: A Randomized, Multi-Center Trial. Nutrients 2022; 14:530. [PMID: 35276889 PMCID: PMC8839689 DOI: 10.3390/nu14030530] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/18/2022] [Accepted: 01/20/2022] [Indexed: 02/04/2023] Open
Abstract
This randomized clinical trial (Registration: NCT03085134) assessed if an extensively hydrolyzed formula (EHF) supplemented with two human milk oligosaccharides (HMO) and reduced protein content (2.20 g/100 kcal) supports normal growth in infants with cow’s milk protein allergy (CMPA). Secondary outcomes were gastrointestinal tolerability, safety, and effect on infections. Nonbreastfed infants aged 0−6 months with CMPA were enrolled. Body weight, length, and head circumference were measured monthly for 4 months (primary study endpoint), after 6 months, and at the age of 12 months. Of 200 infants screened, 194 (mean age 3.2 months) were randomized. At the 4-month follow-up, daily weight gain for the test formula was noninferior to the control formula; p < 0.005. There were no significant group differences in anthropometric parameters. Both formulas were safe and well tolerated. Infants in the HMO group had a statistically significant reduction in the frequency of upper respiratory tract infections and a lower incidence of ear infections at 12 months (per protocol analysis). The relative risk of lower respiratory tract and gastrointestinal infections was reduced by 30−40%, but this was not statistically significant due to sample size limitations. In summary, the HMO-supplemented formula supports normal growth in infants with CMPA and suggests a protective effect against respiratory and ear infections in the first year of life.
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Affiliation(s)
- Yvan Vandenplas
- UZ Brussel KidZ Health Castle, Vrije Universiteit Brussel, 1090 Brussels, Belgium
| | | | - Roberto Berni Canani
- Department of Translational Medical Science, University Federico II, 80131 Naples, Italy;
| | - Siân Ludman
- Royal Devon and Exeter NHS Foundation Trust, Exeter EX2 5DW, UK;
| | | | - Ana Moreno-Álvarez
- Department of Pediatrics, A Coruña University Hospital, 15006 A Coruña, Spain;
| | - Anne E. N. Goh
- KK Women’s and Children’s Hospital, Singapore 229899, Singapore;
| | | | | | - Monika Tadi
- Nestlé Health Science, 1800 Vevey, Switzerland; (M.T.); (R.G.H.)
| | - Ralf G. Heine
- Nestlé Health Science, 1800 Vevey, Switzerland; (M.T.); (R.G.H.)
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