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Nunez H, Nieto PA, Mars RA, Ghavami M, Sew Hoy C, Sukhum K. Early life gut microbiome and its impact on childhood health and chronic conditions. Gut Microbes 2025; 17:2463567. [PMID: 39916516 PMCID: PMC11810090 DOI: 10.1080/19490976.2025.2463567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 12/20/2024] [Accepted: 02/02/2025] [Indexed: 02/12/2025] Open
Abstract
The development of the gut microbiome is crucial to human health, particularly during the first three years of life. Given its role in immune development, disturbances in the establishment process of the gut microbiome may have long term consequences. This review summarizes evidence for these claims, highlighting compositional changes of the gut microbiome during this critical period of life as well as factors that affect gut microbiome development. Based on human and animal data, we conclude that the early-life microbiome is a determinant of long-term health, impacting physiological, metabolic, and immune processes. The early-life gut microbiome field faces challenges. Some of these challenges are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies. Other challenges are methodological: small sample sizes, lack of longitudinal studies, and poor control of confounding variables. To address these limitations, we advocate for more robust research methodologies to better understand the microbiome's role in health and disease. Improved methods will lead to more reliable microbiome studies and a deeper understanding of its impact on health outcomes.
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Affiliation(s)
- Harold Nunez
- Seeding Inc, DBA Tiny Health, Austin, Texas, USA
| | | | - Ruben A. Mars
- Seeding Inc, DBA Tiny Health, Austin, Texas, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Fujita M, Wander K. Lactose in human milk is associated with lower rates of infection during a drought. Ann Hum Biol 2025; 52:2455703. [PMID: 39936580 DOI: 10.1080/03014460.2025.2455703] [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: 08/29/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 02/13/2025]
Abstract
BACKGROUND Infants given mothers' milk have higher resistance against infections than formula-fed counterparts. This protection is likely multifactorial, with roles for both milk immune factors and nutrients, particularly under elevated nutritional and disease stress. AIM This study evaluated several milk nutrients/immune factors to assess associations with infant infectious disease during a severe drought. SUBJECTS AND METHODS The study analysed morbidity recall data from Kenyan mother-infant dyads surveyed during a historic drought (n 84). Predictors of interest in logistic regression models of infant infections included milk sIgA, lactoferrin, retinol, folate receptor-α, fat, protein, and lactose. Adjustment variables included dyadic demographic characteristics and maternal infection. Akaike Information Criterion guided model fit assessment. Interactions between variables were allowed in the best-fit model. RESULTS In the best-fit model, lactose was inversely (OR 0.93; 90% CI 0.89, 0.97), and maternal infection was positively (OR 2.80; 90% CI 1.04, 7.52) associated with infant infection. Milk immune factors (sIgA, lactoferrin) were not included in the final models. CONCLUSION Mothers' milk may protect infants against infection through a broad range of immune and nutrient components. In the context of severe drought with heightened nutritional and disease stress, lactose may protect against infection or decrease in the presence of an infection.
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Affiliation(s)
- Masako Fujita
- Department of Anthropology, Michigan State University, East Lansing, MI, USA
| | - Katherine Wander
- Department of Anthropology, Binghamton University (SUNY), Binghamton, NY, USA
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Li K, Jin J, Liu Z, Chen C, Huang L, Sun Y. Dysbiosis of infant gut microbiota is related to the altered fatty acid composition of human milk from mothers with gestational diabetes mellitus: a prospective cohort study. Gut Microbes 2025; 17:2455789. [PMID: 39834317 PMCID: PMC11776479 DOI: 10.1080/19490976.2025.2455789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 10/13/2024] [Accepted: 01/14/2025] [Indexed: 01/22/2025] Open
Abstract
Gestational diabetes mellitus (GDM) is known to be associated with dysbiosis of offspring gut microbiota, but the mechanism remains unclear. The present prospective study explored the role of human milk fatty acid composition in this association. Mothers with GDM and normal controls were recruited at 24-28 gestational weeks. Follow-up was conducted at 1-3 days postpartum and 1 month postpartum to collect human milk and infant feces. A total of 80 mother-infant pairs (40 in the GDM group and 40 in the normal group) were included in the study. The mothers received guidance on diet and exercise but not drug therapy. All infants were exclusively breastfed. We observed significant differences in 8 phyla and 13 genera in the infant between GDM and normal groups at 1-3 days postpartum or 1 month postpartum. Among these bacteria, significant time × group interaction was observed for 7 phyla (such as Acidobacteriota, Gemmatimonadota, and Myxococcota) and 9 genera (such as Sphingomonas, Allorhizobium Neorhizobium Pararhizobium Rhizobium, and TM7a), after adjusting for confounding factors. Changes in these differential infant bacteria were negatively correlated with changes in C18:3n-3 and total n-3 PUFA levels of breast milk. The increases in C18:3n-3 and total n-3 PUFA levels in human milk over time were much greater in the normal group compared to the GDM group. Our findings indicate that altered human milk fatty acid composition is one important reason for GDM-related dysbiosis of offspring gut microbiota.
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Affiliation(s)
- Kelei Li
- School of Public Health, Qingdao University, Qingdao, China
- Institute of Nutrition and Health, Qingdao University, Qingdao, China
| | - Jin Jin
- School of Public Health, Qingdao University, Qingdao, China
| | - Zhizuo Liu
- Department of Obstetrics, Women and Children’s Hospital Affiliated to Qingdao University, Qingdao, China
| | - Chuanjing Chen
- School of Public Health, Qingdao University, Qingdao, China
| | - Ludi Huang
- School of Public Health, Qingdao University, Qingdao, China
| | - Yongye Sun
- School of Public Health, Qingdao University, Qingdao, China
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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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Medić A, Milićević T, Khraibah A, Herceg Romanić S, Matek Sarić M, Li Y, D'Mello R, Berezovski M, Popović A, Minić Z, Karadžić I. Total proteome and calcium-binding proteins from human breast milk: Exploring the impact of tobacco smoke exposure and environmental factors. Food Chem 2025; 472:142959. [PMID: 39842200 DOI: 10.1016/j.foodchem.2025.142959] [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: 09/20/2024] [Revised: 01/14/2025] [Accepted: 01/16/2025] [Indexed: 01/24/2025]
Abstract
This study integrates proteome analysis of human breast milk (HBM) from a homogeneous group of mothers who are of similar age and live in the same geographical area, along with an analysis of essential and potentially toxic elements in HBM in relation to lifestyle and environmental factors. This preliminary proteomic study, which examined 11 samples of HBM from lactating women, identified a total of 1619 proteins across all samples, revealing significant differences in proteomes influenced by lactation stages, parity, and exposure to tobacco smoke. The pilot study aimed to explore the feasibility of correlating certain proteins with several elements, considered as indicators of tobacco smoke and environmental influences on HBM. Notably, a clear and significant correlation was found between altered calcium content in HBM and the proteome fraction associated with calcium-binding proteins. The findings suggest that all analyzed factors impact the HBM proteome and the activity of certain enzymes.
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Affiliation(s)
- Ana Medić
- University of Belgrade, Faculty of Medicine, Department of Chemistry, Višegradska 26, 11000 Belgrade, Serbia.
| | - Tijana Milićević
- University of Belgrade, Institute of Physics Belgrade, a National Institute of the Republic of Serbia, Pregrevica 118, 11080 Belgrade, Serbia
| | - Abdullah Khraibah
- University of Ottawa, Department of Chemistry and Biomolecular Sciences, John L. Holmes Mass Spectrometry Facility, 10 Marie-Curie, Marion Hall, K1N 6N5 Ottawa, ON, Canada
| | - Snježana Herceg Romanić
- Institute for Medical Research and Occupational Health, Ksaverska Cesta 2, 10001 Zagreb, Croatia
| | - Marijana Matek Sarić
- University of Zadar, Department of Health Studies, Splitska 1, 23000, Zadar, Croatia
| | - Yingxi Li
- University of Ottawa, Department of Chemistry and Biomolecular Sciences, John L. Holmes Mass Spectrometry Facility, 10 Marie-Curie, Marion Hall, K1N 6N5 Ottawa, ON, Canada
| | - Rochelle D'Mello
- University of Ottawa, Department of Chemistry and Biomolecular Sciences, John L. Holmes Mass Spectrometry Facility, 10 Marie-Curie, Marion Hall, K1N 6N5 Ottawa, ON, Canada
| | - Maxim Berezovski
- University of Ottawa, Department of Chemistry and Biomolecular Sciences, John L. Holmes Mass Spectrometry Facility, 10 Marie-Curie, Marion Hall, K1N 6N5 Ottawa, ON, Canada
| | - Aleksandar Popović
- University of Belgrade, Faculty of Chemistry, Studentski trg 12-16, 11000 Belgrade, Serbia
| | - Zoran Minić
- University of Ottawa, Department of Chemistry and Biomolecular Sciences, John L. Holmes Mass Spectrometry Facility, 10 Marie-Curie, Marion Hall, K1N 6N5 Ottawa, ON, Canada.
| | - Ivanka Karadžić
- University of Belgrade, Faculty of Medicine, Department of Chemistry, Višegradska 26, 11000 Belgrade, Serbia
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Martín‐Chamorro RA, Pomar CA, Palou A, Picó C, Rodríguez AM. Impact of Western diet on milk miRNAs and target genes in offspring adipose tissue: modulation by betaine during suckling. Obesity (Silver Spring) 2025; 33:732-742. [PMID: 40025858 PMCID: PMC11937867 DOI: 10.1002/oby.24246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 12/10/2024] [Accepted: 01/02/2025] [Indexed: 03/04/2025]
Abstract
OBJECTIVE We investigated how a maternal Western diet (WD) affects milk microRNA (miRNA) profile and associates with metabolic programming in adipose tissues in pups. We also explored the impact of betaine supplementation during suckling, as betaine levels are reported to be reduced in WD-fed dams' milk. METHODS A microarray analysis was performed to profile miRNA expression in dams' milk. Betaine levels were measured in the milk of dams and the plasma of their offspring. We also analyzed the expression of miRNA target genes in white and brown adipose tissues through gene expression analysis. RESULTS Our findings confirm decreased betaine levels in the milk of WD-fed dams and the plasma of their offspring. The miRNA screening identified 37 deregulated miRNAs (36 downregulated), with the following 6 as the most relevant: miR-223-3p; miR-32-5p; let-7i-5p; miR-140-5p; miR-29a-3p; and miR-29c-3p (downregulated). Some of their target genes were upregulated in brown and white adipose tissues, particularly those related to thermogenesis and browning. Betaine supplementation in pups demonstrated a slight protective effect in females by enhancing thermogenic capacity. CONCLUSIONS Our results underscore the profound impact of a maternal WD on milk miRNA composition, potentially influencing gene expression, thermogenesis, and adiposity in the offspring, with sex-related differences.
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Affiliation(s)
- Rocío A. Martín‐Chamorro
- Laboratory of Molecular Biology, Nutrition and Biotechnology, Nutrigenomics, Biomarkers and Risk Evaluation (NuBE)University of the Balearic IslandsPalmaSpain
- Health Research Institute of the Balearic Islands (IdISBa)PalmaSpain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn)MadridSpain
| | - Catalina A. Pomar
- Laboratory of Molecular Biology, Nutrition and Biotechnology, Nutrigenomics, Biomarkers and Risk Evaluation (NuBE)University of the Balearic IslandsPalmaSpain
- Health Research Institute of the Balearic Islands (IdISBa)PalmaSpain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn)MadridSpain
| | - Andreu Palou
- Laboratory of Molecular Biology, Nutrition and Biotechnology, Nutrigenomics, Biomarkers and Risk Evaluation (NuBE)University of the Balearic IslandsPalmaSpain
- Health Research Institute of the Balearic Islands (IdISBa)PalmaSpain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn)MadridSpain
- Artificial Intelligence Research Institute of the Balearic Islands (IAIB)PalmaSpain
| | - Catalina Picó
- Laboratory of Molecular Biology, Nutrition and Biotechnology, Nutrigenomics, Biomarkers and Risk Evaluation (NuBE)University of the Balearic IslandsPalmaSpain
- Health Research Institute of the Balearic Islands (IdISBa)PalmaSpain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn)MadridSpain
- Artificial Intelligence Research Institute of the Balearic Islands (IAIB)PalmaSpain
| | - Ana M. Rodríguez
- Laboratory of Molecular Biology, Nutrition and Biotechnology, Nutrigenomics, Biomarkers and Risk Evaluation (NuBE)University of the Balearic IslandsPalmaSpain
- Health Research Institute of the Balearic Islands (IdISBa)PalmaSpain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn)MadridSpain
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Mwape RK, Barday MA, van der Zalm MM, Verhagen LM. Overview of mucosal immunity and respiratory infections in children: a focus on Africa. Curr Opin Pediatr 2025; 37:137-144. [PMID: 39907513 PMCID: PMC11888837 DOI: 10.1097/mop.0000000000001438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
PURPOSE OF REVIEW Given the substantial burden of respiratory tract infections (RTIs) on global paediatric health, enhancing our understanding of mucosal immunity can help us advance mucosal biomarkers for diagnosis, prognosis and possible interventions in order to improve health outcomes. This review highlights the critical role of mucosal immunity in paediatric RTIs and recent advances in mucosal interventions, which offer promising strategies to improve outcomes. RECENT FINDINGS The significant burden of paediatric RTIs and growing interest in mucosal immunity advanced our understanding of the role of the respiratory mucosal immune system in protective immunity against RTIs. Studies show that sub-Saharan Africa is disproportionately affected by paediatric RTIs with poverty-associated factors such as human immunodeficiency virus (HIV) and malnutrition as risk factors. Emerging evidence highlights the important role of the respiratory microbiome and mucosal innate and adaptive immune responses in protective immunity against RTIs. SUMMARY The growing interest in mucosal immunity in RTIs has not only advanced our understanding of the overall immune responses in RTIs but also created opportunities to improve RTI care through translation of knowledge from these studies into diagnostics, therapeutics, and vaccines.
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Affiliation(s)
| | - Mish-Al Barday
- Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Marieke M. van der Zalm
- Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Lilly M. Verhagen
- Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Department of Paediatric Infectious Diseases and Immunology, Radboud Community for Infectious Diseases, Amalia Children's Hospital, Radboud University Medical Center
- Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands
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Singh A, Bartlett A, Clifford V, McMullan B, Palasanthiran P. Strategies to reduce CMV infectivity in breastmilk to preterm babies - impact on transmission, nutrients, and bioactivity: a systematic review and meta-analysis. J Perinatol 2025:10.1038/s41372-025-02254-9. [PMID: 40148583 DOI: 10.1038/s41372-025-02254-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 12/10/2024] [Accepted: 02/24/2025] [Indexed: 03/29/2025]
Abstract
INTRODUCTION Postnatal CMV infection (pCMV) acquired via breastmilk is associated with morbidity and mortality in vulnerable infants (<32 weeks or <1500 g). 'Treatment' of breast milk reduces CMV infectivity but quantitative impact on transmission, viral loads, bioactive and nutritional elements is unknown. We conducted a systematic review and meta-analysis to assess how each method impacts CMV transmission rates and viral loads and provide a narrative review of their impact on nutritional and bioactive elements. METHODS Three search strategies for MEDLINE and EMBASE were used to identify articles studying the impact of treatment methods on CMV transmission (Arm A), nutritional elements (Arm B) and bioactive elements (Arm C). Two authors independently screened articles against inclusion and exclusion criteria. Included articles underwent quality assessment using the ROBINS-I tool. Quantitative analysis of data extracted from arm A is presented, alongside narrative reviews of arms B and C. RESULTS Twenty-six studies (n = 3024 infants) were included for arm A. Heat treatment methods and freeze thawing resulted in 82% and 53% reduction CMV transmission respectively, compared to untreated milk. Correlation between viral load magnitude and transmission risk was not significant. Macronutrients remained largely stable after treatment, but bioactive elements were significantly degraded by heat treatment methods. High Pressure Processing was significantly better at preserving bioactive elements compared to heat treatment. CONCLUSION Heat treatment is most effective in reducing CMV infectivity in breastmilk but is associated with higher degradation of bioactive elements, whilst microwave irradiation and HPP eliminate CMV in breastmilk and preserve its immunological integrity.
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Affiliation(s)
- Akshita Singh
- University of New South Wales, Sydney, NSW, Australia
| | - Adam Bartlett
- University of New South Wales, Sydney, NSW, Australia
- Department of Infectious Diseases, Sydney Children's Hospitals Network, Randwick, NSW, Australia
| | - Vanessa Clifford
- Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
- Infection and Immunity, Murdoch Children's Research Institute, Parkville, VIC, Australia
- Laboratory Services, Royal Children's Hospital, Parkville, VIC, Australia
- Australian Red Cross Lifeblood, West Melbourne, VIC, Australia
| | - Brendan McMullan
- University of New South Wales, Sydney, NSW, Australia
- Department of Infectious Diseases, Sydney Children's Hospitals Network, Randwick, NSW, Australia
| | - Pamela Palasanthiran
- University of New South Wales, Sydney, NSW, Australia.
- Department of Infectious Diseases, Sydney Children's Hospitals Network, Randwick, NSW, Australia.
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Shobako M, Kawano K, Taniguchi E, Ohinata K. Medium-chain triglycerides tricaprin TC10 and tricaprylin TC8 attenuated HFD-induced cognitive decline in a manner dependent on or independent of GLP-1. Sci Rep 2025; 15:10381. [PMID: 40140693 DOI: 10.1038/s41598-025-94129-4] [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: 11/29/2024] [Accepted: 03/11/2025] [Indexed: 03/28/2025] Open
Abstract
Population aging is the most important social and medical demographic issue worldwide; therefore, healthy aging is important. The increasing prevalence of dementia and cognitive decline are major health concerns. Medium-chain triglycerides (MCTs) have been shown to improve cognitive decline. The present study investigated the effects and mechanisms of action of orally administered MCTs, including tricaprylin (TC8), tricaprin (TC10), and trilaurin (TC12), on cognitive function in mice fed a high-fat diet (HFD). The administration of TC8 and TC10 attenuated cognitive decline. A relationship has been reported between cognitive dysfunction and impaired glucose metabolism. The administration of TC8 and TC10 also reduced blood glucose levels in the glucose tolerance test. Cognitive improvements by MCTs are widely attributed to the ketogenic effect. In the present study, TC8 significantly increased blood ketone concentrations, whereas TC10 did not. On the other hand, TC10 increased the plasma concentration of glucagon-like peptide-1 (GLP-1), the hormone that promotes insulin secretion. The administration of the GLP-1 receptor antagonist, exendin(9-39), blocked the cognitive-enhancing effects of TC10. These results suggest that TC10 improved cognitive function via the GLP-1 receptor. The in vitro experiment indicated that 2-monocaprin (2-MC10), not TC10, stimulated the secretion of GLP-1 and decreased intracellular cAMP concentrations. In conclusion, we herein demonstrated that TC8 and TC10 attenuated cognitive decline through different mechanisms. This is the first study to suggest that TC10 attenuates cognitive decline via GLP-1.
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Affiliation(s)
- Maiko Shobako
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan
| | - Kohei Kawano
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan
| | - Eriko Taniguchi
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan
| | - Kousaku Ohinata
- Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan.
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García-Alonso CA, Jiménez-López B, Castaño-Duque S, Yepes-Nuñez JJJ, Lampousi AM, Sánchez-Salguero E, Brunck MEG. Mapping the current knowledge on leucocytes in human breastmilk: a scoping review protocol. BMJ Open 2025; 15:e091323. [PMID: 40139704 DOI: 10.1136/bmjopen-2024-091323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/29/2025] Open
Abstract
INTRODUCTION The immunological composition of breastmilk has gained research interest as breastfeeding has been persistently correlated with improved health outcomes in children. Immune cells, also known as leucocytes, are key components of the body's immune system, but they remain understudied in breastmilk. The relevance of breastmilk leucocytes for breastfeeding-mediated immune benefits remains controversial. To identify the current state-of-the-art on breastmilk leucocyte research, unearth knowledge gaps and propose research priorities, a scoping review is necessary. METHODS AND ANALYSIS This scoping review will address the general question of what is known about leucocytes in human breastmilk. The development of this scoping review protocol adhered to the recommendations set forth by the Joanna Briggs Institute guidelines. Peer-reviewed research articles published in English, French or Spanish will be eligible for inclusion in the scoping review. The initial literature search was conducted in January 2024 within the Medline, Embase, Cochrane Central and BVS databases. ETHICS AND DISSEMINATION This review does not require ethics approval. Our dissemination strategy includes peer-review publication and presentations at conferences and to relevant stakeholders. REGISTRATION DETAILS This protocol was registered in Open Science Framework (available at: https://osf.io/kwfsy) on 19 February 2024.
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Affiliation(s)
| | - Brenda Jiménez-López
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Mexico
| | | | - Juan José J Yepes-Nuñez
- School of Medicine, Universidad de los Andes, Bogota, Colombia
- Internal Medicine, Hospital Universitario de la Fundación Santa Fe de Bogotá, Bogota, Colombia
| | - Anna-Maria Lampousi
- Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
| | - Erick Sánchez-Salguero
- Institute for Obesity Research, Tecnológico de Monterrey, Monterrey, Mexico
- University of Oxford Sir William Dunn School of Pathology, Oxford, England, UK
| | - Marion E G Brunck
- Institute for Obesity Research, Tecnológico de Monterrey, Monterrey, Mexico
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Kim KU, Kim J, Jang H, Dan KB, Kim BK, Ji YW, Yi DY, Min H. Protective effects of human breast milk-derived exosomes on inflammatory bowel disease through modulation of immune cells. NPJ Sci Food 2025; 9:34. [PMID: 40113828 PMCID: PMC11926119 DOI: 10.1038/s41538-025-00400-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 02/27/2025] [Indexed: 03/22/2025] Open
Abstract
Human breast milk (HBM)-derived exosomes play a crucial role not only in infant nutrition but also in modulating inflammation, immunity, and epithelial cell protection. This study investigated how HBM-derived exosomes regulate immune cell development and function. The exosomes promoted the differentiation of naïve CD4+ T cells into Treg and Th2 cells while suppressing their differentiation into Th17 and Th1 cells. They also enhanced the proliferation of intestinal epithelial Caco-2 cells and reduced apoptosis in dextran sulfate sodium (DSS)-damaged caco-2 cells. In a DSS-induced colitis mouse model, the exosomes significantly alleviated disease severity, as evidenced by improvements in colon length, disease activity index, and histology grades. Furthermore, the exosomes normalized CD4+ T cell subsets in the spleen, mesenteric lymph nodes, and colon, restoring levels comparable to controls. These findings suggest that HBM-derived exosomes hold promise as a potential therapeutic strategy for inflammatory bowel disease by modulating T-cell responses and protecting intestinal epithelial cells.
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Affiliation(s)
- Ki-Uk Kim
- College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea
| | - Jisu Kim
- College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea
| | - Hyunjun Jang
- College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea
| | - Kang Bin Dan
- College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea
| | - Bo Kyeong Kim
- College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea
| | - Yong Woo Ji
- Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
- Department of Ophthalmology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, 16995, Republic of Korea
| | - Dae Yong Yi
- Department of Pediatrics, Chung-Ang University Hospital, Seoul, 06973, Republic of Korea
- College of Medicine, Chung-Ang University, Seoul, 06972, Republic of Korea
| | - Hyeyoung Min
- College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
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12
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Bertacchi V, Corley M, Aronsen GP, Bribiescas RG. Impact of high temperatures on enzyme-linked immunoassay (ELISA) performance for leptin measurements in human milk stored under varied freeze/thaw conditions. PLoS One 2025; 20:e0320366. [PMID: 40106448 DOI: 10.1371/journal.pone.0320366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 02/17/2025] [Indexed: 03/22/2025] Open
Abstract
Ambient temperature conditions are a common concern during laboratory analysis. Due to unexpected shipping conditions, leptin ELISA kits (Leptin Ultrasensitive, ALPCO USA; Catalog #22-LEPHUU-E01) arrived from the manufacturer at our laboratory at a temperature (76.3°F/24.6°C) well above the 2-8°C conditions recommended by the manufacturer. Since no data are available on the effects of high ambient temperature exposure on the performance of this commercial assay, we opportunistically assessed assay performance using human milk samples. Leptin measurement of recently collected and frozen human milk samples was compared between the warm temperature exposed assay kits and Normal kits that arrived and were stored at recommended temperatures (2-8 °C). We found that assay kit exposure to warm temperature during shipping resulted in sample results that were significantly different from Normal kits despite similar standard curve performance. Measurement variability from human milk samples increased with warmed kits in association with greater freeze/thaw times. This suggests that even under high temperature transportation conditions, this leptin assay performance is robust with kit reagents but compromised with human milk samples. We conclude that kits exposed to high temperature during shipment and/or storage should not be used to run human milk samples and that our concerns may extend to other biological media (i.e., serum, urine, or saliva). This study fills a critical gap in the literature on assay performance validation under non-ideal conditions, such as high temperatures. As global temperatures continue to rise, this question will become more pertinent to research integrity if left unaddressed. In light of our findings, we propose that industry standards for ELISA kit shipping and handling should be evaluated to ensure that all kits are being received in an optimal condition.
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Affiliation(s)
- Victoria Bertacchi
- Reproductive Ecology Laboratory, Department of Anthropology, Yale University, New Haven, Connecticut, United States of America
| | - Margaret Corley
- Reproductive Ecology Laboratory, Department of Anthropology, Yale University, New Haven, Connecticut, United States of America
- Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut, United States of America
| | - Gary P Aronsen
- Reproductive Ecology Laboratory, Department of Anthropology, Yale University, New Haven, Connecticut, United States of America
| | - Richard G Bribiescas
- Reproductive Ecology Laboratory, Department of Anthropology, Yale University, New Haven, Connecticut, United States of America
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13
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Narayanan BL, Ventura JD, Ventura AK. Adaptation of the Remote Food Photography Method to Assess Infant Intake During Bottle-Feeding of Ready-to-Feed Formula. MATERNAL & CHILD NUTRITION 2025:e70016. [PMID: 40097365 DOI: 10.1111/mcn.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 01/17/2025] [Accepted: 02/21/2025] [Indexed: 03/19/2025]
Abstract
Bottle-fed infants are at a higher risk for obesity, yet interventions to modify bottle-feeding patterns have shown limited success. Accurate assessment of bottle-feeding patterns is an important basis for targeted interventions. Caregiver reports are susceptible to bias, highlighting the need for more robust methods. One promising approach is the Remote Food Photography Method (RFPM), which involves analysis of digital photographs to objectively assess intake. The purpose of this study was to adapt RFPM to measure the amount of ready-to-feed formula in bottles. Research assistants took digital photographs of bottles with varying amounts of formula and assessed bottle weight to create a predictive model data set (n = 100) and an external validation data set (n = 100). Image processing software was used to determine the area of formula in pixels. Formula area was regressed on actual bottle weight and the resulting regression parameters were used to calculate estimated bottle weights. Predictive models were validated by applying them to the external validation data set. Within the predictive model data set, the mean difference between estimated and actual bottle weight was equivalent within ±10% equivalence bounds (0.0005 g [90% CI, -0.45, 0.45]). Within the external validation data set, the mean difference between estimated and actual bottle weight was also equivalent within ±10% equivalence bounds (-17.0 g [90% CI, -18.85, -15.17]). Findings were similar when bottle weight was converted to calories. In sum, the present study provided preliminary evidence for the feasibility and accuracy of an adapted RFPM to assess changes in the amount and caloric content of ready-to-feed formula in bottles.
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Affiliation(s)
- Bhagya L Narayanan
- Department of Kinesiology and Public Health, Center for Health Research, California Polytechnic State University, San Luis Obispo, California, USA
| | - Jonathan D Ventura
- Department of Computer Science & Software Engineering, California Polytechnic State University, San Luis Obispo, California, USA
| | - Alison K Ventura
- Department of Kinesiology and Public Health, Center for Health Research, California Polytechnic State University, San Luis Obispo, California, USA
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14
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Graciliano NG, Goulart MOF, de Oliveira ACM. Impact of Maternal Exposure to SARS-CoV-2 on Immunological Components of Breast Milk. Int J Mol Sci 2025; 26:2600. [PMID: 40141241 DOI: 10.3390/ijms26062600] [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: 02/01/2025] [Revised: 03/07/2025] [Accepted: 03/09/2025] [Indexed: 03/28/2025] Open
Abstract
COVID-19, caused by SARS-CoV-2, has become a global public health threat. Although no replication-competent virus has been found in breast milk samples, breastfeeding practices during the pandemic were impacted. It is well known that breast milk is adapted to meet the needs of infants, providing the appropriate amounts of nutrients and various bioactive compounds that contribute to the maturation of the immune system and antioxidant protection, safeguarding infants against diseases. While its composition is variable, breast milk contains immune cells, antibodies, and cytokines, which have anti-inflammatory, pro-inflammatory, antiviral, and antibacterial properties that strengthen infant immunity. Since COVID-19 vaccines have not yet been approved for infants under six months of age, newborns rely on the passive transfer of antibodies via the placenta and breast milk to protect them against severe SARS-CoV-2 infection. Several studies that analyzed breast milk samples in the context of COVID-19 have demonstrated that a strong antibody response is induced following maternal infection with SARS-CoV-2. Therefore, this review aims to provide a comprehensive overview of the impact of maternal exposure to SARS-CoV-2 through natural infection and/or vaccination on the immunological composition of breast milk based on the studies conducted on this topic.
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Affiliation(s)
- Nayara Gomes Graciliano
- Institute of Biological and Health Sciences, Federal University of Alagoas, Maceió 57072-900, Alagoas, Brazil
| | - Marília Oliveira Fonseca Goulart
- Institute of Biological and Health Sciences, Federal University of Alagoas, Maceió 57072-900, Alagoas, Brazil
- Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió 57072-900, Alagoas, Brazil
| | - Alane Cabral Menezes de Oliveira
- Institute of Biological and Health Sciences, Federal University of Alagoas, Maceió 57072-900, Alagoas, Brazil
- College of Nutrition, Federal University of Alagoas, Maceió 57072-900, Alagoas, Brazil
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15
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Krutsch K, Hale TW. Disease Pathophysiology Must Be Considered when Associating Medications with Changes in Milk Composition. Breastfeed Med 2025. [PMID: 40080420 DOI: 10.1089/bfm.2025.0034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/15/2025]
Affiliation(s)
- Kaytlin Krutsch
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Amarillo, Texas, USA
| | - Thomas W Hale
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Amarillo, Texas, USA
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16
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Trofin F, Cianga P, Constantinescu D, Iancu LS, Iancu RI, Păduraru D, Nastase EV, Buzilă ER, Luncă C, Cianga CM, Dorneanu OS. The Legacy of COVID-19 in Breast Milk: The Association of Elevated Anti-Inflammatory and Antimicrobial Proteins with Vaccination or Infection. Curr Issues Mol Biol 2025; 47:182. [PMID: 40136436 PMCID: PMC11941678 DOI: 10.3390/cimb47030182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Breast milk is a rich source of antimicrobial and anti-inflammatory compounds, owing to its diverse array of bioactive molecules. This study explores the presence and activity of natural antimicrobial agents in breast milk, particularly in the context of the SARS-CoV-2 pandemic. MATERIALS AND METHODS Breast milk samples were collected from 50 breastfeeding mothers, including those who had either been vaccinated against SARS-CoV-2 or had recovered from the infection. These samples were compared with a control group consisting of 10 unvaccinated mothers with no history of COVID-19. Key antimicrobial and immune-regulatory proteins-lactoferrin, lactadherin, furin, tenascin C, granzyme B, and chitinase 3-like 1-were quantified using the Luminex multiplex analyzer. RESULTS AND DISCUSSION All targeted biomarkers were detected in breast milk, providing insights into the immune profile transferred to infants following COVID-19 infection or vaccination. These bioactive molecules highlight breastfeeding's role in providing passive immunity and antimicrobial protection. The protein levels were found to be influenced by factors such as maternal inflammation, infant age, delivery mode, and parity, emphasizing the dynamic interaction between maternal immunity, lactation biology, and infant development. CONCLUSION Breastfeeding serves as a powerful anti-SARS-CoV-2 defense mechanism, supported by the activity of lactoferrin, lactadherin, and furin, reinforcing its critical role in child health.
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Affiliation(s)
- Felicia Trofin
- Microbiology Discipline, Preventive Medicine and Interdisciplinarity Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (F.T.); (L.S.I.); (E.R.B.); (C.L.); (O.S.D.)
- “Sf. Spiridon” Clinical Hospital, 700111 Iasi, Romania; (D.C.); (R.I.I.); (C.M.C.)
| | - Petru Cianga
- “Sf. Spiridon” Clinical Hospital, 700111 Iasi, Romania; (D.C.); (R.I.I.); (C.M.C.)
- Immunology Discipline, Ist Morpho-Functional Sciences Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
| | - Daniela Constantinescu
- “Sf. Spiridon” Clinical Hospital, 700111 Iasi, Romania; (D.C.); (R.I.I.); (C.M.C.)
- Immunology Discipline, Ist Morpho-Functional Sciences Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
| | - Luminița Smaranda Iancu
- Microbiology Discipline, Preventive Medicine and Interdisciplinarity Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (F.T.); (L.S.I.); (E.R.B.); (C.L.); (O.S.D.)
- Iasi Regional Center for Public Health, National Institute of Public Health, 700465 Iasi, Romania
| | - Roxana Irina Iancu
- “Sf. Spiridon” Clinical Hospital, 700111 Iasi, Romania; (D.C.); (R.I.I.); (C.M.C.)
- Phisiopathology Discipline, IInd Morpho-Functional Sciences Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
| | - Diana Păduraru
- “Dr. C.I. Parhon” Clinical Hospital, 700503 Iasi, Romania;
| | - Eduard Vasile Nastase
- Clinical Hospital of Infectious Diseases “Sf. Parascheva”, 700116 Iasi, Romania;
- Infectious Diseases Discipline, Medical Sciences II Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
| | - Elena Roxana Buzilă
- Microbiology Discipline, Preventive Medicine and Interdisciplinarity Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (F.T.); (L.S.I.); (E.R.B.); (C.L.); (O.S.D.)
- Iasi Regional Center for Public Health, National Institute of Public Health, 700465 Iasi, Romania
| | - Cătălina Luncă
- Microbiology Discipline, Preventive Medicine and Interdisciplinarity Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (F.T.); (L.S.I.); (E.R.B.); (C.L.); (O.S.D.)
- “Sf. Maria” Children Emergency Hospital, 700309 Iasi, Romania
| | - Corina Maria Cianga
- “Sf. Spiridon” Clinical Hospital, 700111 Iasi, Romania; (D.C.); (R.I.I.); (C.M.C.)
- Immunology Discipline, Ist Morpho-Functional Sciences Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
| | - Olivia Simona Dorneanu
- Microbiology Discipline, Preventive Medicine and Interdisciplinarity Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (F.T.); (L.S.I.); (E.R.B.); (C.L.); (O.S.D.)
- Clinical Hospital of Infectious Diseases “Sf. Parascheva”, 700116 Iasi, Romania;
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17
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Naftaly S, Pery T, Mhajne R, Ashkar A, Davidovich-Pinhas M, Zinger A. Harnessing the Potential of Human Breast Milk to Boost Intestinal Permeability for Nanoparticles and Macromolecules. J Control Release 2025; 379:768-785. [PMID: 39842727 DOI: 10.1016/j.jconrel.2025.01.049] [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: 06/25/2024] [Revised: 01/17/2025] [Accepted: 01/18/2025] [Indexed: 01/24/2025]
Abstract
The intricate interplay between human breast milk, nanoparticles, and macromolecules holds promise for innovative nutritional delivery strategies. Compared to bovine milk and infant formula, this study explores human breast milk's role in modulating intestinal permeability and its impact on nanoparticle and macromolecule transport. Comparative analysis with bovine milk and infant formula reveals significant elevations in permeability with human breast milk, accompanied by a decrease in transepithelial electrical resistance, suggesting enhanced paracellular transport. Mechanistically, human breast milk reduces Zonula occludens-1 levels, suggesting a regulatory role in intestinal barrier function. Through in vitro and ex vivo evaluations, we aim to understand better the mechanisms behind enhanced permeability and how human breast milk affects nanoparticle physicochemical properties, potentially modulating their behavior. Specifically, human breast milk improves the intestinal permeability of liposomes in a porcine intestinal model, with associated changes in the composition of milk proteins corona related to liposome charge. These findings underscore the unexploited potential of human breast milk in facilitating transport across the intestinal barrier, offering novel avenues for human nutritional delivery and therapeutic interventions.
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Affiliation(s)
- Si Naftaly
- Laboratory for Bioinspired Nano Engineering and Translational Therapeutics, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel
| | - Topaz Pery
- Laboratory for Bioinspired Nano Engineering and Translational Therapeutics, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel
| | - Rawan Mhajne
- Laboratory for Bioinspired Nano Engineering and Translational Therapeutics, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel
| | - Areen Ashkar
- Faculty of Biotechnology and Food Engineering, Technion, Israel
| | - Maya Davidovich-Pinhas
- Faculty of Biotechnology and Food Engineering, Technion, Israel; Russell-Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa 3200003, Israel
| | - Assaf Zinger
- Laboratory for Bioinspired Nano Engineering and Translational Therapeutics, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel; Russell-Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa 3200003, Israel; Cardiovascular Sciences Department, Houston Methodist Academic Institute, Houston, TX 77030, United States; Neurosurgery Department, Houston Methodist Academic Institute, Houston, TX 77030, United States; Resnick Sustainability Center of Catalysis, Technion-Israel Institute of Technology, Haifa 3200003, Israel; Bruce and Ruth Rappaport Cancer Research Center, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
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18
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Aldana-Parra F, Olaya Vega G, Fewtrell M. Effectiveness of a new breastfeeding counselling intervention on breastfeeding prevalence, infant growth velocity and postpartum weight loss in overweight women: a randomized controlled trial. Int Breastfeed J 2025; 20:14. [PMID: 40051012 PMCID: PMC11887114 DOI: 10.1186/s13006-025-00703-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 02/03/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Maternal overweight is a risk factor for child obesity. Breastfeeding may decrease this risk, but breastfeeding prevalence is low in overweight or obese mothers. METHODS We conducted a randomized trial in 90 overweight/obese pregnant women in Bogotá-Colombia during 2019, to evaluate the effects of a new exclusive breastfeeding (EBF) counselling intervention for overweight/obese mothers, based on Carl Rogers' client-centered theory. The Intervention included individualized breastfeeding counseling, empowerment sessions, and a set of problem-solving strategies based on Carl Rogers' client-centered theory, conducted during late pregnancy, first week postpartum, 1 and 3 months postpartum. Primary outcomes were EBF during the last 24 h prevalence at 4 months postpartum, infant growth, and maternal weight loss at 4 months postpartum; secondary outcomes were serum and breast milk prolactin concentration, breast milk energy and macronutrient content, estimated breast milk volume at 1 and 4 months and EBF prevalence at interim time-points. Mothers were randomised in late pregnancy to intervention (new breastfeeding counselling; IG) or control group (standard breastfeeding support; CG). RESULTS The IG had significantly higher EBF prevalence at 4 months (82.8%) compared to the CG (30.6%) (Prevalence ratio or PR = 2.7; 95% CI = 1.6, 4.5). There were no intervention effects on infant growth velocity, maternal weight loss or secondary outcomes. DISCUSSION The intervention, which could be implemented in primary care settings, was highly effective for increasing the prevalence of EBF in overweight/obese mothers at 4 months postpartum. The results should, however, be interpreted in the context of the small sample size, short follow-up period and loss to follow-up. Further evaluation of the intervention is required in a larger sample including longer-term infant follow-up. TRIAL REGISTRATION (UTN) U1111-1228-9913 20 February 2019; ISRCTN15922904, retrospectively registered.
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Affiliation(s)
- Fanny Aldana-Parra
- Department of Nutrition and Biochemistry, Pontificia Universidad Javeriana, Bogotá, Colombia.
| | - Gilma Olaya Vega
- Department of Nutrition and Biochemistry, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Mary Fewtrell
- Childhood Nutrition Research group, Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK
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19
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Saigh BH. Breastfeeding duration and neurodevelopment: insights into autism spectrum disorders and weaning practices. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:62. [PMID: 40033428 DOI: 10.1186/s41043-025-00784-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 02/02/2025] [Indexed: 03/05/2025]
Abstract
This paper examines the complex relationship between breastfeeding duration and the incidence of autism spectrum disorders (ASDs), focusing on identifying the most beneficial weaning period and its subsequent effects on child development. Breastfeeding is widely recognized for its role in promoting early health, strengthening the immune system, and supporting neurodevelopment. However, the debate over its optimal duration persists. Integrating insights from current scientific studies with interpretations of Qur'anic teachings, this study advocates for a breastfeeding duration of 21 months. This duration balances the benefits of extended breastfeeding with potential risks associated with prolonged exposure, reflecting both ancient wisdom and contemporary evidence. Key findings suggest that breastfeeding may play a preventive role in mitigating ASD symptoms and enhancing neurodevelopment through mechanisms such as immune regulation, microbiome diversity, and hormonal pathways. These insights underline the need for further specialized research to explore the long-term impacts of breastfeeding on ASD-related outcomes.
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Affiliation(s)
- Budor H Saigh
- Department of Special Education, College of Education, Umm Al-Qura University, Makkah, Saudi Arabia.
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20
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Apaydin Cirik V, Turkmen AS, Alirkiliçarslan DB. Effectiveness of breast milk in the healing of medical adhesive-related skin injuries in peripheral intravenous catheter securement: A randomized controlled trial. Nurs Crit Care 2025; 30:e13113. [PMID: 38924216 DOI: 10.1111/nicc.13113] [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: 12/25/2022] [Revised: 05/28/2024] [Accepted: 06/03/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND Skin injuries, which are more prevalent among premature infants, can prolong the hospital stay of preterms in neonatal intensive care units. AIM This study aimed to assess the effectiveness of breast milk in reducing the healing time of skin injuries caused using medical adhesive for securing peripheral intravenous catheters (PIVCs) in late preterm infants, which was evaluated using the Neonatal Skin Condition Scale (NSCS). A randomized controlled trial was conducted with two parallel groups in a 1:1 allocation ratio. STUDY DESIGN It was conducted in the Neonatal Intensive Care Unit of a hospital in Karaman, Turkey between August and November 2022 with 72 preterm infants born at 35-36 weeks with stable health status and having intravenous catheter securement to the skin with medical adhesive tapes, with the tapes remaining on the skin for a minimum of 24 h and a maximum of 32 h. Preterm infants were randomly assigned to breast milk or routine care groups. The site of the skin injuries was evaluated by two independent observers using the NSCS once every 60 min until the injury was completely healed. A one-way ANOVA and repeated measures analysis of variance was used to analyse the data. RESULTS The average postnatal age was 3.32 ± 0.99 days, and the total duration of medical adhesive tape on the skin was 28.21 ± 2.59 h. A significant difference was found between the mean skin condition scale scores of the infants in the breast milk group (F = 117.219, p < .001) and the routine care group (F = 122.247, p < .001) according to time within the group. The skin injuries of preterm infants in the breast milk group decreased significantly in the first 3 h after the procedure. CONCLUSION Breast milk application was more effective than routine care in reducing the healing time of skin injuries. RELEVANCE TO CLINICAL PRACTICE It can be recommended to use breast milk to heal skin injuries in preterm infants.
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Affiliation(s)
- Vildan Apaydin Cirik
- Department of Midwifery, Child Health and Disease Nursing, Faculty of Health Sciences, Karamanoğlu Mehmetbey University, Karaman, Türkiye
| | - Ayse Sonay Turkmen
- Nursing Department, Child Health and Disease Nursing, Health Science Faculty, Karamanoglu Mehmetbey University, Karaman, Türkiye
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21
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Al-Jaber H, Bacha R, Al-Mannai WA, Al-Mansoori L. Beyond nutrition: The emerging therapeutic potential landscape of breast milk-derived extracellular vesicles. Nutr Res 2025; 135:42-51. [PMID: 39923728 DOI: 10.1016/j.nutres.2025.01.006] [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: 10/04/2024] [Revised: 01/08/2025] [Accepted: 01/09/2025] [Indexed: 02/11/2025]
Abstract
Breastfeeding is widely recognized for its essential nutritional benefits and broader biological impacts. Beyond providing infants with a balanced mix of vitamins, proteins, and fats critical for growth and development, breast milk contains bioactive extracellular vesicles (BMEVs). These membrane-bound particles, rich in proteins, lipids, and nucleic acids, play a pivotal role in immune modulation, intercellular communication, and the overall development of the infant's immune system. This review explores the emerging therapeutic potential of BMEVs, highlighting their capacity to modulate recipient cell functions, influence immune responses, and contribute to overall infant health. Preclinical evidence suggests that these vesicles can prevent and manage conditions such as necrotizing enterocolitis, allergies, and viral infections, which are common in early childhood. Furthermore, BMEVs offer promise as vehicles for targeted drug delivery, enhancing the efficacy of therapeutic interventions. Despite the growing body of evidence, challenges such as the need for standardized isolation methods, characterization techniques, and larger-scale clinical studies persist, hindering the translation of this research into clinical practice. This review addresses these challenges and discusses future directions, emphasizing the need for comprehensive mechanistic studies to fully realize the potential of BMEVs as novel therapeutic agents and biomarkers of health. Ultimately, these vesicles represent a promising frontier in maternal and child health, with potential applications extending far beyond traditional nutrition. By harnessing their unique properties, BMEVs could revolutionize infant care, offering new strategies for disease prevention and innovative therapeutic interventions that enhance infant health outcomes.
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Affiliation(s)
- Hend Al-Jaber
- Biomedical Research Center, Qatar University, Doha, Qatar
| | - Rim Bacha
- Biomedical Research Center, Qatar University, Doha, Qatar; College of Medicine, QU Health, Qatar University, Doha, Qatar; College of Health Sciences, Qatar University, Doha, Qatar
| | | | - Layla Al-Mansoori
- Biomedical Research Center, Qatar University, Doha, Qatar; College of Medicine, QU Health, Qatar University, Doha, Qatar.
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22
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Ilgaz F, Höller A, Marsaux C, Banta‐Wright S, Coşkun T, Dingess KA, Jörg‐Streller M, Newby C, Singh R, Stahl B, Szwec C, van Wegberg A, Woestenenk W, MacDonald A, Karall D. Human Milk Feeding in Inherited Metabolic Disorders: A Systematic Review of Growth, Metabolic Control, and Neurodevelopment Outcomes. J Inherit Metab Dis 2025; 48:e70001. [PMID: 39912448 PMCID: PMC11800321 DOI: 10.1002/jimd.70001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 11/21/2024] [Accepted: 01/09/2025] [Indexed: 02/07/2025]
Abstract
Human milk (HM) is the optimal source of nutrition for infants. Yet the suitability of HM macronutrient composition, paired with the challenge of regulating HM intake, may deserve some consideration for infants with inherited metabolic disorders (IMDs) requiring restrictive and controlled dietary management. Except for classic galactosemia, HM feeding is expected to be feasible, allowing infants to maintain metabolic stability, while growing and developing optimally. However, information about HM feeding in nonphenylketonuria (PKU) literature is scarce. In this systematic review, 52 studies were included, representing 861 infants (86% PKU) receiving HM after IMD diagnosis (mean duration 4-10 months depending on the IMD). For non-PKU IMDs (e.g., other amino acidopathies, urea cycle disorders, organic acidemias, fatty acid oxidation disorders), outcomes of HM feeding were available for few infants, except for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (n = 48). In PKU, HM feeding combined with phenylalanine-free formula, led to adequate metabolic control (25 studies), growth (15 studies), and neurodevelopment (10 studies). For other IMDs, more evidence is required, but the limited data suggest that HM feeding is possible, with attentive monitoring and disease-specific formula supplementation where applicable. In MCAD deficiency, ensuring adequate HM intake is essential, as symptoms were more frequently reported in exclusively breastfed infants. No IMD-specific articles were found on the relationship between HM feeding and many other outcomes of interest (e.g., immune status or comorbidity risk later in life). With the exception of galactosemia, HM feeding is expected to benefit infants with IMD. More data should be published for IMDs other than PKU.
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Affiliation(s)
- Fatma Ilgaz
- Department of Nutrition and Dietetics, Faculty of Health SciencesHacettepe UniversityAnkaraTurkey
| | - Alexander Höller
- Division of Nutrition and DieteticsUniversity Hospital InnsbruckInnsbruckAustria
- Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology AssessmentUMIT TIROL‐University for Health Sciences and TechnologyHall in TirolAustria
- Digital Health Information Systems, Center for Health & Bioresources, AIT Austrian Institute of TechnologyGrazAustria
| | | | | | - Turgay Coşkun
- Department of Pediatric Metabolism and NutritionHacettepe University Faculty of MedicineAnkaraTurkey
| | | | - Monika Jörg‐Streller
- Division of Nutrition and DieteticsUniversity Hospital InnsbruckInnsbruckAustria
| | - Camille Newby
- Department of Nutrition and DieteticsBristol Royal Hospital for ChildrenBristolUK
| | - Rani Singh
- Department of Human Genetics and PediatricsEmory University School of MedicineAtlantaGeorgiaUSA
| | - Bernd Stahl
- Danone Research & InnovationUtrechtthe Netherlands
- Department of Chemical Biology & Drug DiscoveryUtrecht Institute for Pharmaceutical Sciences, Utrecht UniversityUtrechtthe Netherlands
| | - Clare Szwec
- Danone Research & InnovationUtrechtthe Netherlands
| | - Annemiek van Wegberg
- Division of Metabolic DiseasesBeatrix Children's Hospital, University Medical Centre Groningen, University of GroningenGroningenthe Netherlands
- Department of Gastroenterology and Hepatology‐DieteticsRadboud University Medical CenterNijmegenthe Netherlands
| | | | - Anita MacDonald
- Department of DieteticsBirmingham Women's and Children's HospitalBirminghamUK
| | - Daniela Karall
- Department of Pediatrics I, Division of Inherited Metabolic DisordersMedical University of InnsbruckInnsbruckAustria
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Puri K, Svenstrup C, Vanderpool C. Functional Infant Formula Additives. Neoreviews 2025; 26:e163-e171. [PMID: 40020744 DOI: 10.1542/neo.26-3-020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2025] [Accepted: 11/04/2025] [Indexed: 03/03/2025]
Abstract
Breastfeeding is the ideal initial feeding method for providing nutrition to full-term infants and is recommended by major health organizations, including the American Academy of Pediatrics and the World Health Organization. Despite improvements in global breastfeeding rates, many infants still receive formula. Significant advancements have been achieved in the safety and nutritional content of modern formulas. Various functional additives, such as human milk oligosaccharides, milk fat globule membrane, docosahexaenoic acid, and lactoferrin, are used with the aim to replicate some of the benefits of breast milk. These additives enhance formula by providing benefits beyond basic nutrition. The aim of this review is to summarize these additives and their impact on infant nutrition and development.
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Affiliation(s)
- Kanika Puri
- Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana
| | - Courtney Svenstrup
- Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana
| | - Charles Vanderpool
- Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana
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24
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Paul A, Bui T, Muelbert M, Toldi G. T lymphocytes in human milk: Their role in immune system maturation through maternal microchimerism. J Reprod Immunol 2025; 168:104451. [PMID: 39951899 DOI: 10.1016/j.jri.2025.104451] [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: 10/22/2024] [Revised: 01/08/2025] [Accepted: 02/07/2025] [Indexed: 02/17/2025]
Abstract
Breastfeeding promotes the trafficking of immune cells and soluble factors from the mother to the neonate during lactation, resulting in maternal microchimerism. Human milk is abundant in T lymphocytes, but little is known about their priming and actions in neonatal mucosal tissues and their role in conferring immune tolerance in early life. This review summarises recent findings on the characteristics of human milk T cells compared to their counterparts in maternal and neonatal blood. We discuss how bioactive components of human milk, such as cytokines, hormones, and miRNA, may modulate the immune suppressive function of this cell subset. We shed light on the presence and possible functions of regulatory T cells (Tregs) in the breastfeeding triad of mother, human milk, and neonate, and how this subset of T lymphocytes may contribute to the prevention of immune pathologies, such as allergies and autoimmune diseases, later in life through human milk-induced maternal microchimerism in the newborn.
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Affiliation(s)
- Ayamita Paul
- Liggins Institute, University of Auckland, Auckland, New Zealand
| | - Tram Bui
- Liggins Institute, University of Auckland, Auckland, New Zealand
| | - Mariana Muelbert
- Liggins Institute, University of Auckland, Auckland, New Zealand
| | - Gergely Toldi
- Liggins Institute, University of Auckland, Auckland, New Zealand.
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25
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Chetta KE. Historical Perspectives and the Road to Current Breakthroughs in Human Milk Research. Breastfeed Med 2025; 20:170-174. [PMID: 39969984 DOI: 10.1089/bfm.2025.0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
Human milk (HM) research has its origins in the early 20th century, emerging from the field of dairy science. Early pioneers such as Drs. David Forsyth, Lucy Naish, and Disney Cran were among the first to formally study HM, building on centuries of recognition of its importance. Clinicians such as Dr. Ruth A. Lawrence, a true "giant" in the field, played a pivotal role in translating HM research into medical education and clinical practice. This commentary highlights the milestones, key contributors, technical advancements, and future directions of HM research, tracing its journey from modest beginnings to its establishment as a rapidly evolving scientific discipline.
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Affiliation(s)
- Katherine E Chetta
- Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Medical University of South Carolina, Shawn Jenkins Children's Hospital, Charleston, South Carolina, USA
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26
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Ryan N, O’Mahony S, Leahy-Warren P, Philpott L, Mulcahy H. The impact of perinatal maternal stress on the maternal and infant gut and human milk microbiomes: A scoping review. PLoS One 2025; 20:e0318237. [PMID: 40019912 PMCID: PMC11870360 DOI: 10.1371/journal.pone.0318237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 01/14/2025] [Indexed: 03/03/2025] Open
Abstract
BACKGROUND Perinatal maternal stress, which includes both psychological and physiological stress experienced by healthy women during pregnancy and the postpartum period, is becoming increasingly prevalent. Infant early exposure to adverse environments such as perinatal stress has been shown to increase the long-term risk to metabolic, immunologic and neurobehavioral disorders. Evidence suggests that the human microbiome facilitates the transmission of maternal factors to infants via the vaginal, gut, and human milk microbiomes. The colonization of aberrant microorganisms in the mother's microbiome, influenced by the microbiome-brain-gut axis, may be transferred to infants during a critical early developmental period. This transfer may predispose infants to a more inflammatory-prone microbiome which is associated with dysregulated metabolic process leading to adverse health outcomes. Given the prevalence and potential impact of perinatal stress on maternal and infant health, with no systematic mapping or review of the data to date, the aim of this scoping review is to gather evidence on the relationship between perinatal maternal stress, and the human milk, maternal, and infant gut microbiomes. METHODS This is an exploratory mapping scoping review, guided by the Joanna Briggs Institute's methodology along with use of the Prisma Scr reporting guideline. A comprehensive search was conducted using the following databases, CINAHL Complete; MEDLINE; PsycINFO, Web of Science and Scopus with a protocol registered with Open Science Framework DOI 10.17605/OSF.IO/5SRMV. RESULTS After screening 1145 papers there were 7 paper that met the inclusion criteria. Statistically significant associations were found in five of the studies which identify higher abundance of potentially pathogenic bacteria such as Erwinia, Serratia, T mayombie, Bacteroides with higher maternal stress, and lower levels of stress linked to potentially beneficial bacteria such Lactococcus, Lactobacillus, Akkermansia. However, one study presents conflicting results where it was reported that higher maternal stress was linked to the prevalence of more beneficial bacteria. CONCLUSION This review suggests that maternal stress does have an impact on the alteration of abundance and diversity of influential bacteria in the gut microbiome, however, it can affect colonisation in different ways. These bacterial changes have the capacity to influence long term health and disease. The review analyses data collection tools and methods, offers potential reasons for these findings as well as suggestions for future research.
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Affiliation(s)
- Niamh Ryan
- School of Nursing and Midwifery, University College Cork, Cork, Ireland
| | - Siobhain O’Mahony
- Department of Anatomy and Neuroscience, APC Microbiome Ireland, University College Cork, Cork, Ireland
| | | | - Lloyd Philpott
- School of Nursing and Midwifery, University College Cork, Cork, Ireland
| | - Helen Mulcahy
- School of Nursing and Midwifery, University College Cork, Cork, Ireland
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27
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Hernandez AM, Berto MI, Bianchini EMG. Viscosity study of maternal and formula milks according to the assessment proposed by the International Dysphagia Diet Standardisation Initiative Model: a comparison with Rheological Assessment. Codas 2025; 37:e20240049. [PMID: 40008695 PMCID: PMC11864768 DOI: 10.1590/2317-1782/e20240049en] [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: 03/16/2024] [Accepted: 11/10/2024] [Indexed: 02/27/2025] Open
Abstract
PURPOSE The present study aimed to investigate the behavior and the viscosity classification of liquids recommended for infants, up to six months, in Brazil, and their formulations used in Videofluoroscopy Swallowing Studies. METHODS Breast milk from different gestational and breastfeeding time, two regular infant formulas, and one anti-reflux formula were evaluated in five different formulations: pure, mixed with liquid barium sulfate, in two proportions (20 and 33%), thickened with a specific thickener for neonates and thickened and mixed with 20% liquid barium sulfate, using the International Dysphagia Diet Standardisation Initiative model. The results were compared with data obtained from a previous rheological study. RESULTS The breast milk samples and the infant formulas, in pure presentation, exhibited similar behavior except for the anti-reflux formula. The thickened samples with the addition of barium and the pure liquid barium sulfate exhibited the highest viscosity among the formulations. The increase in viscosity with the addition of barium occurred for all samples and for the thickened formulations, but not in linear behavior. The results showed minor differences of IDDSI classification compared to the findings obtained in the rheological study. CONCLUSION The present study revealed the variability of liquid viscosity across different formulations, supporting the idea of the importance of this knowledge in videofluoroscopic assessment. It has also highlighted the risk associated with using a subjective method in preparing the stimuli offered, allowing for greater reliability in diagnosing swallowing dynamics in neonates and infants. This approach may help prevent inaccurate diagnoses and harmful interventions.
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Affiliation(s)
- Ana Maria Hernandez
- Programa de Estudos Pós-graduados em Fonoaudiologia, Pontifícia Universidade de São Paulo - São Paulo (SP), Brasil.
| | - Maria Isabel Berto
- Instituto de Tecnologia de Alimentos, Centro de Tecnologia de Laticínios - Campinas (SP), Brasil.
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28
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Talbert JA, Townsend SD. Human milk as a complex natural product. Nat Prod Rep 2025; 42:406-420. [PMID: 39831434 DOI: 10.1039/d4np00058g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
Covering: up to the end of 2024Breastfeeding is one of the most effective ways to promote child health. However, characterizing the chemistry that fortifies the benefits of breastfeeding remains a grand challenge. Current efforts in the community are focused on characterizing the roles of the different carbohydrates, proteins, and fats in milk. The goal of this review is to highlight and describe current knowledge about the major classes of macromolecules in human milk and their potential role in infant health and wellness.
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Affiliation(s)
- Julie A Talbert
- Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, USA.
| | - Steven D Townsend
- Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, USA.
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29
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Valentine CJ. Research on Human milk feeding to drive impactful immune health and outcomes in vulnerable preterm infants should evaluate maternal confounders. Pediatr Res 2025:10.1038/s41390-025-03932-2. [PMID: 39972152 DOI: 10.1038/s41390-025-03932-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 01/27/2025] [Indexed: 02/21/2025]
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Wang R, Sun S, Zhang Q, Wu G, Ren F, Chen J. Maternal Milk Orchestrates the Development of Infant Gut Microbiota: Implications for Health and Future Research Directions. RESEARCH (WASHINGTON, D.C.) 2025; 8:0558. [PMID: 39975576 PMCID: PMC11836195 DOI: 10.34133/research.0558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 11/28/2024] [Accepted: 12/04/2024] [Indexed: 02/21/2025]
Abstract
Human breast milk serves as a vital source of nutrition for infants, and it also plays a critical role in shaping the infant gut microbiota and establishing intestinal homeostasis. This process substantially impacts immune function, neurodevelopment, and overall health. The noninvasive nature of breast milk collection makes it an ethical and accessible area for research, positioning it as a key focus for future studies. These future directions include the identification of novel bacteria combination, the establishment of comprehensive databases on infant microbiota, and the use of computational models to predict interactions between breast milk components and the gut microbiome. Additionally, the creation of diverse biological models and the establishment of infant stool banks will further enhance understanding of host-microbiome interactions and support disease prevention strategies.
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Affiliation(s)
- Ran Wang
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health,
China Agricultural University, Beijing 100190, China
| | - Siyuan Sun
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health,
China Agricultural University, Beijing 100190, China
| | - Qi Zhang
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health,
China Agricultural University, Beijing 100190, China
| | - Guanglei Wu
- College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Government,
China Agricultural University, Beijing 100083, China
| | - Fazheng Ren
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health,
China Agricultural University, Beijing 100190, China
| | - Juan Chen
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health,
China Agricultural University, Beijing 100190, China
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31
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Petersohn I, Wang P, van Heumen C, van Lee L, Hettinga KA, Belzer C, van Baar A, Feskens E, Brouwer-Brolsma EM. MELK study: an observational study on human milk composition and infant health determinants during the first year of life in a Dutch cohort. BMJ Open 2025; 15:e091487. [PMID: 39965946 PMCID: PMC11836862 DOI: 10.1136/bmjopen-2024-091487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/05/2024] [Indexed: 02/20/2025] Open
Abstract
INTRODUCTION Human milk plays a crucial role in infants' nutrition and immunity, with its composition being influenced by different factors. The role of maternal diet on human milk fatty acid composition, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is well studied. Higher fish intake is associated with higher DHA levels in human milk, while fewer associations have been reported for EPA. Yet, maternal diet's impact on human milk composition for other nutrients is understudied, and variations in sampling protocols and study quality hinder definitive conclusions on its overall impact. Ethnicity may also impact milk composition, with different dietary habits intertwined with different genetic backgrounds, but also here research lacks standardised protocols. Our study aims to investigate maternal diet, ethnicity, and their association with human milk composition, along with their potential short-term associations with infant health and development, through detailed dietary assessment and by recruiting participants from diverse backgrounds. Understanding these associations could inform the development of tailored nutritional guidelines for mothers and infants, ultimately promoting optimal health and well-being for both. The study design, with its strict sampling procedure, can guide and inspire future studies. METHODS AND ANALYSIS We will conduct an observational study involving 120 healthy mothers from three ethnic backgrounds (Chinese, Caucasian and Turkish), exclusively breastfeeding their 2-month-old infants. We will collect human milk samples at two time points and assess maternal dietary intake over 4 days. Additionally, we will collect data on various maternal and child characteristics, including maternal stress, socioeconomic status and health, and infant feeding, sleeping, crying, gastrointestinal health and developmental status. ETHICS AND DISSEMINATION The study has been approved by the Medical Ethical Committee Oost-Nederland (NL79447.091.21), and all participants provided written informed consent before entering the study. Findings will be widely disseminated at international conferences and meetings including the annual Nutrition & Growth conference, ESPGHAN, and through publication in scientific peer-reviewed journals. TRIAL REGISTRATION NUMBER ISRCTN registry (ISRCTN35735283).
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Affiliation(s)
- Inga Petersohn
- Human Nutrition and Health, Wageningen University & Research, Wageningen, Gelderland, The Netherlands
- Ausnutria B.V, Zwolle, The Netherlands
| | - Peiheng Wang
- Food Quality and Design, Wageningen University & Research, Wageningen, Gelderland, The Netherlands
| | - Cindy van Heumen
- Human Nutrition and Health, Wageningen University & Research, Wageningen, Gelderland, The Netherlands
| | | | - Kasper Arthur Hettinga
- Food Quality and Design, Wageningen University & Research, Wageningen, Gelderland, The Netherlands
| | - Clara Belzer
- Microbiology, Wageningen University, Wageningen, Gelderland, The Netherlands
| | - Anneloes van Baar
- Child and Adolescent Studies, Utrecht University, Utrecht, Utrecht, The Netherlands
| | - Edith Feskens
- Human Nutrition and Health, Wageningen University & Research, Wageningen, Gelderland, The Netherlands
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32
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Zhang P, Jian H, Li C, Yao L, He T, Tan Z, Zhou J, Yin Y. Effect of hepatitis B virus infection on the nutrient composition of human breast milk: A prospective cohort study. Food Chem 2025; 465:141947. [PMID: 39577257 DOI: 10.1016/j.foodchem.2024.141947] [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: 06/07/2024] [Revised: 10/31/2024] [Accepted: 11/05/2024] [Indexed: 11/24/2024]
Abstract
There are limited data regarding the impact of Hepatitis B virus (HBV) infection on the composition of human breast milk, and there is no international consensus on the nutritional management of newborns of HBV-positive mothers. We hypothesised that HBV infection can alter the composition of breast milk and that newborns require additional nutritional supplements for healthy growth. We conducted a prospective observational cohort study that recruited 150 pregnant women with HBV infection and matched them with a healthy control group. Multivariate linear regression analysis revealed that glucose and albumin concentrations were increased in the HBV group (av. 4.65 mmol/L and av. 5.66 g/L, respectively), whereas lactoferrin concentrations decreased (av. 537.68 pg/mL). Therefore, additional lactoferrin supplementation may be necessary for newborns delivered to women with HBV infection.
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Affiliation(s)
- Peizhen Zhang
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Huiqi Jian
- Department of Gynecology, Jiangmen Central Hospital, China
| | - Chuo Li
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Lin Yao
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Tiantian He
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Zhangmin Tan
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
| | - Jin Zhou
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
| | - Yuzhu Yin
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
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Calcaterra V, Cena H, Pirazzi A, Sottotetti F, Cordaro E, Cavallo C, Milanta C, El Masri D, Conti MV, Vandoni M, Zuccotti G. From Pregnancy to Breastfeeding: The Role of Maternal Exercise in Preventing Childhood Obesity. Nutrients 2025; 17:660. [PMID: 40004988 PMCID: PMC11858060 DOI: 10.3390/nu17040660] [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: 12/29/2024] [Revised: 01/22/2025] [Accepted: 02/11/2025] [Indexed: 02/27/2025] Open
Abstract
Low adherence to healthy lifestyle behaviors during pregnancy and lactation is strongly associated with a higher risk of childhood obesity. This narrative review aims to elucidate and summarize the pivotal role played by physical activity (PA) during pregnancy and breastfeeding, highlighting the potential mechanisms linking PA in these periods to the prevention of childhood obesity. Maternal exercise during pregnancy and breastfeeding significantly reduces the risk of childhood obesity by enhancing fetal metabolism, supporting healthy maternal weight management, and promoting improved breastfeeding practices. Pregnancy and the postpartum period represent critical windows for implementing preventive strategies that benefit both the mother and child. Encouraging an active lifestyle during pregnancy and breastfeeding is a vital public health strategy with extensive benefits. Healthcare professionals play a crucial role in creating supportive environments and providing tailored guidance to empower mothers to engage in regular PA. This approach not only enhances individual health outcomes but also contributes to the broader goal of fostering healthier communities.
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Affiliation(s)
- Valeria Calcaterra
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy; (V.C.); (E.C.)
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milano, Italy; (C.M.); (G.Z.)
| | - Hellas Cena
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (H.C.); (F.S.); (D.E.M.); (M.V.C.)
- Clinical Nutrition and Dietetics Unit, ICS Maugeri IRCCS, 27100 Pavia, Italy
| | - Agnese Pirazzi
- Laboratory of Adapted Motor Activity (LAMA), Department of Public Health, Experimental Medicine and Forensic Science, University of Pavia, 27100 Pavia, Italy; (A.P.); (C.C.)
| | - Francesca Sottotetti
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (H.C.); (F.S.); (D.E.M.); (M.V.C.)
| | - Erika Cordaro
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy; (V.C.); (E.C.)
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milano, Italy; (C.M.); (G.Z.)
| | - Caterina Cavallo
- Laboratory of Adapted Motor Activity (LAMA), Department of Public Health, Experimental Medicine and Forensic Science, University of Pavia, 27100 Pavia, Italy; (A.P.); (C.C.)
| | - Chiara Milanta
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milano, Italy; (C.M.); (G.Z.)
| | - Dana El Masri
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (H.C.); (F.S.); (D.E.M.); (M.V.C.)
| | - Maria Vittoria Conti
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (H.C.); (F.S.); (D.E.M.); (M.V.C.)
| | - Matteo Vandoni
- Laboratory of Adapted Motor Activity (LAMA), Department of Public Health, Experimental Medicine and Forensic Science, University of Pavia, 27100 Pavia, Italy; (A.P.); (C.C.)
| | - Gianvincenzo Zuccotti
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milano, Italy; (C.M.); (G.Z.)
- Department of Biomedical and Clinical Science, University of Milano, 20157 Milano, Italy
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Sinha B, Mazumder S, Thakur A, Devi S, More D, Ashorn P, Sommerfelt H, Kurpad A, Bhandari N. Effect of kangaroo mother care in low birth weight infants on human milk intake: a randomized controlled trial. Am J Clin Nutr 2025:S0002-9165(25)00074-7. [PMID: 39947481 DOI: 10.1016/j.ajcnut.2025.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 01/13/2025] [Accepted: 02/07/2025] [Indexed: 03/05/2025] Open
Abstract
BACKGROUND It is plausible that one of the key biological pathways through which kangaroo mother care (KMC) improves health outcomes in low birth weight (LBW) infants is by enhancing human milk intake and quality. This hypothesis needs to be tested. OBJECTIVES This study aims to estimate the effect of promotion and support of KMC in LBW infants compared with control during the neonatal period on human milk intake and human milk components. METHODS We randomly assigned 550 LBW infants (1500-2250 g) to the intervention arm with promotion of and support for continuous skin-to-skin contact and exclusive breastfeeding through home visits or to no such intervention (control) during the neonatal period. All infants received routine home-based postnatal care visits. We estimated human milk intake by the infant over a 14-d period using the deuterium dilution technique and measured the concentration of carbohydrate, protein and amino acids, fat, lactoferrin, and secretory immunoglobulin A (sIgA) in human milk of a subsample of 250 mothers. RESULTS The mean infant human milk intake was 331 ± 144 g/d or 142 ± 57 g/kg/d in the control arm and 368 ± 135 g/d or 154 ± 50 g/kg/d in the intervention arm participants, yielding a mean difference of 37 [95% confidence interval (CI): 12, 63] g/d or 12 (95% CI: 2, 22) g/kg/d. The mean concentration of carbohydrate in human milk in the intervention arm was 51.2 ± 6.1 g/L against 50 ± 6.8 g/L in the control arm. The corresponding values for protein were 15.0 ± 2.9 g/L and 16.3 ± 4.6 g/L, respectively. We did not find any substantial differences in the concentration of amino acids, fat, lactoferrin, or sIgA between the study arms. CONCLUSIONS Our findings show that KMC is associated with a substantially higher human milk intake in LBW infants during the neonatal period. There was no evidence of any effect of KMC on the concentration of several human milk components. This trial was registered at Clinical Trials Registry-India as CTRI/2017/04/008430.
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Affiliation(s)
- Bireshwar Sinha
- Society for Applied Studies, New Delhi, India; DBT/Wellcome India Alliance Clinical and Public Health Fellow, Hyderabad, India.
| | | | | | - Sarita Devi
- Division of Nutrition, St. John's Research Institute, Bangalore, India
| | - Deepak More
- Society for Applied Studies, New Delhi, India
| | - Per Ashorn
- Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, and Tampere University Hospital, Tampere, Finland
| | - Halvor Sommerfelt
- Centre for Intervention Science in Maternal and Child Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Cluster for Global Health, Division for Health Services, Norwegian Institute of Public Health, Oslo, Norway
| | - Anura Kurpad
- Division of Nutrition, St. John's Research Institute, Bangalore, India
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Gilfillan M, Wenhold FAM, Mulol H, Feucht UD. Maternal Phenotype, Infant Size and Breast Milk Composition in Women Living With HIV. MATERNAL & CHILD NUTRITION 2025:e13807. [PMID: 39925234 DOI: 10.1111/mcn.13807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 11/22/2024] [Accepted: 01/13/2025] [Indexed: 02/11/2025]
Abstract
The impact of maternal factors on the size of HIV-exposed-uninfected (HEU) infants and breast milk composition is poorly understood. Anthropometry, bio-electrical impedance, haemoglobin and HIV viral load data of women living with HIV (WLWH) and without HIV (WLWOH) were compared and related to their infants' anthropometric Z-scores and breast milk macronutrients 6 weeks and 6 months postnatally. At both time points, WLWH (6-week: n = 83; 6-month: n = 63) had lower reactance (measure of body cell mass) (6-week: p = 0.016; 6-month: p < 0.001), phase angle (PhA) (measure of cell health) (6-week: p = 0.001; 6-month: p = 0.002) and haemoglobin (6-week: p = 0.002; 6-month: p = 0.004) than WLWOH (6-week: n = 90; 6-month: n = 73). HEU infants had lower weight-for-age Z-scores (WAZ) (6-week: p = 0.010; 6-month: p = 0.005). Breast milk composition did not differ between groups. At 6 weeks, HEU infants had lower head circumference-for-age Z-scores (HCAZ) (p = 0.014). Bivariate regression demonstrated maternal HIV predicted lower infant WAZ (ß = -0.442; p = 0.011) and HCAZ (ß = -0.445; p = 0.014). Maternal body mass index (BMI) and mid-upper arm circumference were positively associated with breast milk protein content (ß = 0.018; p = 0.014 and ß = 0.025; p = 0.002, respectively). At 6 months (bivariate regression) maternal HIV predicted lower infant WAZ (ß = -0.609; p = 0.005) and length-for-age Z-scores (ß = -0.741; p = 0.018). Higher maternal BMI and PhA were associated with higher infant WAZ (ß = 0.622; p = 0.015 and ß = 0.055; p = 0.017, respectively). On multivariable analysis, maternal HIV remained a predictor of lower WAZ (ß = -0.568; p = 0.024). In conclusion, maternal HIV infection and phenotype predict the size of infants and breast milk composition up to 6 months postnatally.
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Affiliation(s)
- Marlene Gilfillan
- Department of Human Nutrition, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
- Department of Human Nutrition, Gauteng Department of Health, Kalafong Provincial Tertiary Hospital, Pretoria, South Africa
- Research Centre for Maternal, Fetal, Newborn and Child Health Care Strategies, Kalafong Provincial Tertiary Hospital, University of Pretoria, Pretoria, South Africa
- Maternal and Infant Health Care Strategies Unit, South African Medical Research Council, Pretoria, South Africa
| | - Friedeburg A M Wenhold
- Department of Human Nutrition, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
- Research Centre for Maternal, Fetal, Newborn and Child Health Care Strategies, Kalafong Provincial Tertiary Hospital, University of Pretoria, Pretoria, South Africa
- Maternal and Infant Health Care Strategies Unit, South African Medical Research Council, Pretoria, South Africa
| | - Helen Mulol
- Research Centre for Maternal, Fetal, Newborn and Child Health Care Strategies, Kalafong Provincial Tertiary Hospital, University of Pretoria, Pretoria, South Africa
- Maternal and Infant Health Care Strategies Unit, South African Medical Research Council, Pretoria, South Africa
- Department of Paediatrics, University of Pretoria, Pretoria, South Africa
| | - Ute D Feucht
- Research Centre for Maternal, Fetal, Newborn and Child Health Care Strategies, Kalafong Provincial Tertiary Hospital, University of Pretoria, Pretoria, South Africa
- Maternal and Infant Health Care Strategies Unit, South African Medical Research Council, Pretoria, South Africa
- Department of Paediatrics, University of Pretoria, Pretoria, South Africa
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Wang Y, Xing X, Ren X, Jiang S, Yang Z, Lai J. Different Chemical Forms of Thiamine, Riboflavin, and Folate in Human Milk as a Function of Lactation Stages-A Cohort Study on Breastfeeding Women from Beijing. Nutrients 2025; 17:624. [PMID: 40004953 PMCID: PMC11857878 DOI: 10.3390/nu17040624] [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: 01/11/2025] [Revised: 02/07/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
Background: The function and bioavailability of water-soluble vitamins in human milk (HM) is contingent upon their specific molecular configurations. This study aims to investigate the concentrations of different forms of thiamine, riboflavin, and folate in HM and to elucidate the temporal variations of these nutrients across different stages of lactation. Methods: A cohort of 35 healthy mother-infant pairs from Beijing was recruited, and 214 HM samples were collected. The concentrations of water-soluble vitamins in these samples were analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A mixed linear regression model was employed to examine the relationship between HM vitamin levels and lactation stages. Results: This study analyzed the concentrations of free thiamine, thiamine monophosphate (TMP), thiamine pyrophosphate (TPP), free riboflavin, flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), 5-methyl-tetrahydrofolate (5-MTHF), tetrahydrofolate (THF), 5-formyl-tetrahydrofolate (5-fTHF), 5,10-methenyl-tetrahydrofolate (5,10-MTHF), and unmetabolized folic acid (UMFA) at various lactation stages (0-7 days, 15 days, 30 days, 60 days, 90 days, 120 days, 150 days, and 180 days). Free thiamine concentrations increased from colostrum to 180 days, while total thiamine rose during the first month and then stabilized. Free and total riboflavin levels remained relatively constant throughout lactation. Free and total folate concentrations peaked at 90 days and subsequently declined. Significant correlations were observed between follow-up time and changes in free thiamine, free folate, and total folate concentrations over 180 days. Conclusions: This study provides detailed data on the concentrations and trends of free and total thiamine, riboflavin, and folate in HM from 0 to 180 days postpartum, highlighting the dynamic nature of vitamin concentrations in HM. No deficiencies in these HM vitamins were detected in the surveyed population. Future further research will be conducted to reveal the correlation between different forms of water-soluble vitamins in HM and dietary factors.
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Affiliation(s)
- Ye Wang
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China; (Y.W.); (X.X.); (X.R.); (S.J.); (Z.Y.)
- Key Laboratory of Human Breast Milk Science, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Xinxin Xing
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China; (Y.W.); (X.X.); (X.R.); (S.J.); (Z.Y.)
- Key Laboratory of Human Breast Milk Science, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Xiangnan Ren
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China; (Y.W.); (X.X.); (X.R.); (S.J.); (Z.Y.)
- Key Laboratory of Human Breast Milk Science, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Shan Jiang
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China; (Y.W.); (X.X.); (X.R.); (S.J.); (Z.Y.)
- Key Laboratory of Human Breast Milk Science, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Zhenyu Yang
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China; (Y.W.); (X.X.); (X.R.); (S.J.); (Z.Y.)
- Key Laboratory of Human Breast Milk Science, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Jianqiang Lai
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China; (Y.W.); (X.X.); (X.R.); (S.J.); (Z.Y.)
- Key Laboratory of Human Breast Milk Science, Chinese Center for Disease Control and Prevention, Beijing 100050, China
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Deferm N, Dinh J, Pansari A, Jamei M, Abduljalil K. Postpartum changes in maternal physiology and milk composition: a comprehensive database for developing lactation physiologically-based pharmacokinetic models. Front Pharmacol 2025; 16:1517069. [PMID: 39963246 PMCID: PMC11830814 DOI: 10.3389/fphar.2025.1517069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 01/16/2025] [Indexed: 02/20/2025] Open
Abstract
Introduction Pharmacotherapy during lactation often lacks reliable drug safety data, resulting in delayed treatment or early cessation of breastfeeding. In silico tools, such as physiologically-based pharmacokinetic (PBPK) models, can help to bridge this knowledge gap. To increase the accuracy of these models, it is essential to account for the physiological changes that occur throughout the postpartum period. Methods This study aimed to collect and analyze data on the longitudinal changes in various physiological parameters that can affect drug distribution into breast milk during lactation. Following meta-analysis of the collated data, mathematical functions were fitted to the available data for each parameter. The best-performing functions were selected through numerical and visual diagnostics. Results and Discussion The literature search identified 230 studies, yielding a dataset of 36,689 data points from 20,801 postpartum women, covering data from immediately after childbirth to 12 months postpartum. Sufficient data were obtained to describe postpartum changes in maternal plasma volume, breast volume, cardiac output, glomerular filtration rate, haematocrit, human serum albumin, alpha-1-acid glycoprotein, milk pH, milk volume, milk fat, milk protein, milk water content, and daily infant milk intake. Although data beyond 7 months postpartum were limited for some parameters, mathematical functions were generated for all parameters. These functions can be integrated into lactation PBPK models to increase their predictive power and better inform medication efficacy and safety for breastfeeding women.
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Affiliation(s)
- Neel Deferm
- Predictive Technologies Division, Certara UK Limited, Sheffield, United Kingdom
- Pharmides BV, Pelt, Belgium
| | - Jean Dinh
- Predictive Technologies Division, Certara UK Limited, Sheffield, United Kingdom
- School of Pharmacy, Department of Pharmacy, University of Washington, Seattle, WA, United States
| | - Amita Pansari
- Predictive Technologies Division, Certara UK Limited, Sheffield, United Kingdom
| | - Masoud Jamei
- Predictive Technologies Division, Certara UK Limited, Sheffield, United Kingdom
| | - Khaled Abduljalil
- Predictive Technologies Division, Certara UK Limited, Sheffield, United Kingdom
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de Castro LS, Horta BL, Paiva RDF, Rocha ACL, Desai M, Ross MG, Coca KP. Donor Human Milk Fat Content Is Associated with Maternal Body Mass Index. Breastfeed Med 2025; 20:126-132. [PMID: 39587962 DOI: 10.1089/bfm.2024.0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
Introduction: Donor human milk is increasingly being utilized for both preterm and term infants when mother's milk is unavailable. With the rising prevalence of maternal overweight and obesity, it is crucial to evaluate the relationship between maternal body mass index and the fat and energy content of donor human milk. Objectives: To assess the impact of maternal body mass index on human milk fat content. Methods: A cross-sectional study was carried out using retrospective data from women who made their first human milk donation at ≥15 days postpartum at a human milk bank in São Paulo, Brazil, from January 2018 to December 2020. Data of sociodemographic, obstetric, health, and anthropometric measures were collected by the human milk bank staff. Milk fat and energy content were determined using the crematocrit test. Analysis of variance and multiple linear regression were used to compare means of crematocrit and fat. We determined the p-values using a test of heterogeneity and linear trend and presented the one with the lower p-value. Results: Most donors were between 25 and 35 years old, had higher education, were employed, and lived with a partner. At the time of milk donation, 40.9% of women were overweight or obese. The fat (1.09 g/dL) and energy (9.83 kcal/dL) content of human milk were higher in obese donor compared with eutrophic donors. Conclusions: The fat and energy content of human milk were associated with maternal body mass index, suggesting the potential value for selective use of high fat and high calorie donor milk for very low birthweight or premature infants.
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Affiliation(s)
- Lucíola Sant'Anna de Castro
- Ana Abrão Breastfeeding Center/Human Milk Bank, Escola Paulista de Enfermagem-School of Nursing, Universidade Federal de São Paulo, São Paulo, Brazil
| | | | - Rebeca de Freitas Paiva
- Department of Pediatrics, School of Medicine, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Ana Carolina Lavio Rocha
- Ana Abrão Breastfeeding Center/Human Milk Bank, Escola Paulista de Enfermagem-School of Nursing, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Mina Desai
- Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles at Harbor-UCLA, Torrance, California, USA
- The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA
| | - Michael G Ross
- Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles at Harbor-UCLA, Torrance, California, USA
- The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA
- Department of Obstetrics and Gynecology, Charles R. Drew University, Los Angeles, California, USA
| | - Kelly Pereira Coca
- Ana Abrão Breastfeeding Center/Human Milk Bank, Escola Paulista de Enfermagem-School of Nursing, Universidade Federal de São Paulo, São Paulo, Brazil
- Department of Women's Health Nursing, Escola Paulista de Enfermagem - School of Nursing, Universidade Federal de São Paulo, São Paulo, Brazil
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Kumari-Maurya S, Annapure US, Gupta S. Nutrient composition of human milk of Indian mothers: relation with maternal and infant anthropometry. JOURNAL OF FOOD SCIENCE AND TECHNOLOGY 2025; 62:273-282. [PMID: 39868392 PMCID: PMC11757815 DOI: 10.1007/s13197-024-06025-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 05/28/2024] [Accepted: 06/27/2024] [Indexed: 01/28/2025]
Abstract
The aim of the study was to determine the nutrient composition of human milk (HM) of Indian mothers and investigate its association with maternal and infant anthropometric measures. Human milk is an ideal source of nutrition for optimum growth and development of infant. Among Indian mothers, HM composition data is scanty, especially during prolonged lactation. Mother-infant dyads (n = 50) comprising of two lactation group (0-6 m, n = 26) and (7-12 m, n = 24) residing in Delhi, India were enrolled. Height, weight, BMI, MUAC and head circumference were measured and compared with reference standard. The macronutrients and micronutrients of HM were analysed using MIRIS analyzer, ICP-AES and HPLC. Correlation plots were generated between HM nutrients and maternal, infant anthropometry. Mean BMI of mothers were 19.6 ± 2.6 (0-6 m) and 21.2 ± 3.7 (7-12 m) kg/m2. Around 26% of mothers were underweight, 28% overweight. Among infants, 26% were underweight, wasted (18%), stunted (34%) and overweight (10%). The macronutrient composition of human milk were similar to reference values (means ± standard deviation). Both lactation group showed similar HM nutrient composition. Significant positive associations (r = 0.3-0.5) were found between maternal height, infant HCZ with HM energy, fat; maternal prepregnancy-weight, MUAC with retinol; maternal MUAC with crude protein.
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Affiliation(s)
- Suman Kumari-Maurya
- Department of Food Engineering and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, 400019 India
| | - Uday S. Annapure
- Department of Food Engineering and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, 400019 India
- Institute of Chemical Technology, Marathwada Campus, Jalna, 431213 India
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Brambilla MM, Perrone S, Shulhai AM, Ponzi D, Paterlini S, Pisani F, Rollo D, Pelosi A, Street ME, Palanza P. Systematic review on Endocrine Disrupting Chemicals in breastmilk and neuro-behavioral development: Insight into the early ages of life. Neurosci Biobehav Rev 2025; 169:106028. [PMID: 39880346 DOI: 10.1016/j.neubiorev.2025.106028] [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: 09/26/2024] [Revised: 01/10/2025] [Accepted: 01/23/2025] [Indexed: 01/31/2025]
Abstract
Breast milk (BM) is the main nutrition source for infants that plays a key role on growth and development. Human milk composition includes endogenous and exogenous substances, including endocrine disrupting chemicals (EDCs). EDCs are man-made environmental chemicals present in everyday environment and food that can disrupt the programming of endocrine signalling pathways during development, resulting in adverse effects that may not be apparent until much later in life. The presence of single and/or mixtures of EDCs in BM has been shown to be associated with impairment of reproductive, metabolic, immunologic system and neurobehavioral developmental outcomes. This systematic review discusses the current knowledge about the presence of EDCs in BM, and their potential effects on infant outcomes during the first six years of life. Following PRISMA guidelines, we made a systematic evaluation of the literature on the effects of single and mixtures EDC on (i) mental and psychomotor development; (ii) socio-communicative and behavioral development. Negative association between EDC exposure and developmental areas considered emerged highlighting: (i) BM as a potential key matrix for the monitoring of EDC exposure (ii) the short- and long-term negative effect on infant neuro-behavioral outcomes, and (iii) the importance of public health efforts to reduce maternal and infant EDC exposure. However, heterogeneous results found emphasizes the need to further longitudinal studies to consider factors that can lower EDC exposure or exert a protective role on infant neurodevelopment, and to better understand the mechanism behind the EDCs and its effects on infant development.
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Affiliation(s)
- M Maddalena Brambilla
- Department of Medicine and Surgery, University of Parma, Parma 43126, Italy; University Hospital of Parma (AOUPR), Parma 43126, Italy.
| | - Serafina Perrone
- Department of Medicine and Surgery, University of Parma, Parma 43126, Italy; University Hospital of Parma (AOUPR), Parma 43126, Italy
| | - Anna-Mariia Shulhai
- Department of Medicine and Surgery, University of Parma, Parma 43126, Italy; University Hospital of Parma (AOUPR), Parma 43126, Italy
| | - Davide Ponzi
- Department of Medicine and Surgery, University of Parma, Parma 43126, Italy
| | - Silvia Paterlini
- Department of Medicine and Surgery, University of Parma, Parma 43126, Italy
| | - Francesco Pisani
- Department of Medicine and Surgery, University of Parma, Parma 43126, Italy
| | - Dolores Rollo
- Department of Medicine and Surgery, University of Parma, Parma 43126, Italy
| | - Annalisa Pelosi
- Department of Medicine and Surgery, University of Parma, Parma 43126, Italy
| | - Maria Elisabeth Street
- Department of Medicine and Surgery, University of Parma, Parma 43126, Italy; University Hospital of Parma (AOUPR), Parma 43126, Italy
| | - Paola Palanza
- Department of Medicine and Surgery, University of Parma, Parma 43126, Italy
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da Silva Júnior WF, de Oliveira Costa KM, Castro Oliveira HM, Antunes MM, Mafra K, Nakagaki BN, Corradi da Silva PS, Megale JD, de Sales SC, Caixeta DC, Martins MM, Sabino-Silva R, de Paula CMP, Goulart LR, Rezende RM, Menezes GB. Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligands. J Lipid Res 2025; 66:100744. [PMID: 39814317 PMCID: PMC11849619 DOI: 10.1016/j.jlr.2025.100744] [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: 07/17/2024] [Revised: 01/03/2025] [Accepted: 01/08/2025] [Indexed: 01/18/2025] Open
Abstract
The liver plays a central role in fat storage, but little is known about physiological fat accumulation during early development. Here we investigated a transient surge in hepatic lipid droplets observed in newborn mice immediately after birth. We developed a novel model to quantify liver fat content without tissue processing. Using high-resolution microscopy assessed the spatial distribution of lipid droplets within hepatocytes. Lugol's iodine staining determined the timing weaning period, and milk deprivation experiments investigated the relationship between milk intake and fat accumulation. Lipidomic analysis revealed changes in the metabolic profile of the developing liver. Finally, we investigated the role of Toll-like receptor 4 (TLR4) signaling in fat storage using knockout mice and cell-specific deletion strategies. Newborn mice displayed a dramatic accumulation of hepatic lipid droplets within the first 12 h after birth, persisting for the initial two weeks of life. This pattern coincided with exclusive milk feeding and completely abated by the third week, aligning with weaning. Importantly, the observed fat accumulation shared characteristics with established models of pathological steatosis, suggesting potential biological relevance. Lipid droplets were primarily localized within the cytoplasm of hepatocytes. Milk deprivation experiments demonstrated that milk intake is the primary driver of this transient fat accumulation. Lipidomic analysis revealed significant changes in the metabolic profile of newborn livers compared to adults. Interestingly, several highly abundant lipids in newborns were identified as putative ligands for TLR4. Subsequent studies using TLR4-deficient mice and cell-specific deletion revealed that TLR4 signaling, particularly within hepatocytes, plays a critical role in driving fat storage within the newborn liver. Additionally, a potential collaboration between metabolic and immune systems was suggested by the observed effects of myeloid cell-specific TLR4 ablation. This study demonstrates a unique phenomenon of transient hepatic fat accumulation in newborn mice driven by milk intake and potentially regulated by TLR4 signaling, particularly within hepatocytes.
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Affiliation(s)
- Wanderson Ferreira da Silva Júnior
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Karen Marques de Oliveira Costa
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Hortência Maciel Castro Oliveira
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Maísa Mota Antunes
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Kassiana Mafra
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Brenda Naemi Nakagaki
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Pedro Sérgio Corradi da Silva
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Júlia Duarte Megale
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Sarah Campos de Sales
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Douglas Carvalho Caixeta
- Innovation Center in Salivary Diagnostics and Nanobiotechnology, Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
| | - Mário Machado Martins
- Laboratory of Nanobiotechnology, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, Brazil
| | - Robinson Sabino-Silva
- Innovation Center in Salivary Diagnostics and Nanobiotechnology, Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
| | - Cristina Maria Pinto de Paula
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Luiz Ricardo Goulart
- Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
| | - Rafael Machado Rezende
- Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Gustavo Batista Menezes
- Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
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Capra ME, Aliverti V, Bellani AM, Berzieri M, Montani AG, Pisseri G, Sguerso T, Esposito S, Biasucci G. Breastfeeding and Non-Communicable Diseases: A Narrative Review. Nutrients 2025; 17:511. [PMID: 39940369 PMCID: PMC11819769 DOI: 10.3390/nu17030511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 01/27/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
INTRODUCTION Breastfeeding plays a fundamental role in newborns' and infants' health. Breast milk's protective power against malnutrition and its positive effect on neurological and physical development are well established and are reflected in the policy statements of all major pediatric health entities. However, breastfeeding also plays an important role in the prevention of so-called non-communicable diseases, such as obesity, hypertension, dyslipidemia, and autoimmune diseases. METHODS This narrative review aims to analyze the effect of breastfeeding and breast milk on the development of non-communicable diseases, with a special focus on weight excess, dyslipidemia, allergy, and gastrointestinal diseases. This narrative review was carried out through three steps: executing the search, examining abstracts and full texts, and analyzing results. To achieve this, the databases PubMed, EMBASE, Scopus, ScienceDirect, Web of Science, and Google Scholar were explored to collect and select publications from 1990 to 2024 to find pertinent studies in line with this review's development. The search included randomized placebo-controlled trials, controlled clinical trials, double-blind, randomized controlled studies, and systematic reviews. A total of 104 manuscripts were ultimately included in the analysis. RESULTS Breastfeeding is associated with a decreased vulnerability to early viral infections or chronic inflammatory conditions during preschool years, a reduced incidence of weight excess, and likely lower cholesterol concentration, besides having a small protective effect against systolic blood hypertension. CONCLUSIONS Pediatricians must promote breastfeeding, support the mother-infant dyad, and consider breast milk as a real "health voucher" that can last lifelong. However, further studies are needed to better define the extent and duration of breastfeeding's protective power in this context.
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Affiliation(s)
- Maria Elena Capra
- Pediatrics and Neonatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy; (M.E.C.); (G.B.)
| | - Valentina Aliverti
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Arianna Maria Bellani
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Martina Berzieri
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Anna Giuseppina Montani
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Gianlorenzo Pisseri
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Tullia Sguerso
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Susanna Esposito
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Giacomo Biasucci
- Pediatrics and Neonatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy; (M.E.C.); (G.B.)
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
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Ishisaka A, Fujiwara N, Mukai R, Nishikawa M, Ikushiro S, Murakami A. Flavonoids in breast milk and their absorption, metabolism, and bioactivity in infants. Biosci Biotechnol Biochem 2025; 89:165-173. [PMID: 39375845 DOI: 10.1093/bbb/zbae140] [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: 09/15/2024] [Accepted: 09/26/2024] [Indexed: 10/09/2024]
Abstract
Flavonoids are present in plant foods such as vegetables and fruits and exhibit various physiological effects, including antioxidant and anti-inflammatory properties. Ingested flavonoids are absorbed from the intestinal tract and circulated in the blood. Some studies have indicated the presence of flavonoids in breast milk. However, information on their metabolites and concentrations in breast milk and the subsequent transfer to and physiological functions in infants is limited. Therefore, this review presents a compilation of recent findings on the transfer of flavonoids to infants via breast milk and their bioactivities.
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Affiliation(s)
- Akari Ishisaka
- Department of Food Science and Nutrition, School of Human Science and Environment, University of Hyogo, Himeji, Hyogo, Japan
- Research Institute for Food and Nutritional Sciences, University of Hyogo, Himeji, Hyogo, Japan
| | - Nao Fujiwara
- Department of Food Science and Nutrition, School of Human Science and Environment, University of Hyogo, Himeji, Hyogo, Japan
| | - Rie Mukai
- Department of Food Science, Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Tokushima, Tokushima, Japan
| | - Miyu Nishikawa
- Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, Imizu, Toyama, Japan
| | - Shinichi Ikushiro
- Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, Imizu, Toyama, Japan
| | - Akira Murakami
- Department of Food Science and Nutrition, School of Human Science and Environment, University of Hyogo, Himeji, Hyogo, Japan
- Research Institute for Food and Nutritional Sciences, University of Hyogo, Himeji, Hyogo, Japan
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Urashima T, Ajisaka K, Ujihara T, Nakazaki E. Recent advances in the science of human milk oligosaccharides. BBA ADVANCES 2025; 7:100136. [PMID: 39991261 PMCID: PMC11847054 DOI: 10.1016/j.bbadva.2024.100136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 12/20/2024] [Accepted: 12/25/2024] [Indexed: 02/25/2025] Open
Abstract
Human colostrum and mature milk contain oligosaccharides (Os), designated as human milk oligosaccharides (HMOs). Approximately 200 varieties of HMOs have been characterized. Although HMOs are not utilized as an energy source by infants, they have important protective functions, including pathogenic bacteria and viral infection inhibitors and immune modulators, among other functions, and HMOs stimulate brain-nerve development. The Os concentration is average 11 g/L in human milk but >100 mg/L in mature bovine milk, which is used to manufacture infant formula, suggesting that human-identical milk oligosaccharides (HiMOs) should be incorporated into milk substitutes. Some infant formulas incorporating 2'-fucosyllactose and lacto-N-neotetraose are now commercially available, and intervention trials have been concluded. We review basic HMO information, including their chemical structures and concentrations, attempts to synthesize HMOs at small and plant scale, studies that clarified HMO biological functions, and interventions with milk substitutes incorporating HiMOs in formula-fed infants.
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Affiliation(s)
- Tadasu Urashima
- Department of Food and Life Science, Obihiro University of Agriculture and Veterinary Medicine, Nishi2sen 11banchi, Inada cho, Obihiro, Hokkaido, 080-8555, Japan
| | - Katsumi Ajisaka
- Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-Ku, Niigata City, Niigata, 956-8603, Japan
| | - Tetsuro Ujihara
- Kyowa Hakko Bio Co., Ltd. 4-10-2, Nakano-ku, Nakano, Tokyo, 164-0001, Japan
| | - Eri Nakazaki
- Kyowa Hakko Bio Co., Ltd. 4-10-2, Nakano-ku, Nakano, Tokyo, 164-0001, Japan
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45
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Sosanya ME, Adesanya OD, Rufai HE, Freeland-Graves JH. A Mobile-Based Approach to Enhance Knowledge of Infant and Young Child Feeding Among Teenage Mothers in Nigeria: A Randomized Controlled Trial. Nutrients 2025; 17:414. [PMID: 39940272 PMCID: PMC11820066 DOI: 10.3390/nu17030414] [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: 01/05/2025] [Revised: 01/18/2025] [Accepted: 01/20/2025] [Indexed: 02/14/2025] Open
Abstract
Background/Objectives: The second highest prevalence of childhood malnutrition in the world is found in Nigeria. Infant and young child feeding practices (IYCF) are crucial predictors of the nutritional status of children. This study evaluated the effects of utilization of the BabyThrive app versus control on IYCF knowledge of Nigerian teenage mothers. Methods: A parallel, randomized controlled trial was conducted with 194 low-income teenage mother-child (0-2 years) dyads in Nigeria. Outcome measures included knowledge concerning food type for an infant, exclusive breastfeeding, complementary feeding, and total IYCF knowledge scores. Results: No significant differences in demographic characteristics or IYCF knowledge were found at baseline. Post-intervention, almost all BabyThrive participants vs. only 36.1% of controls were aware that expressed breast milk is the ideal food for an infant <6 months, when a mother resumes work (p < 0.05). As compared to the BabyThrive group, knowledge of how to maintain breast milk supply (5.2% vs. 83.5%), the duration of safety of breast milk at room temperature (15.4% vs. 85.6%), responsive feeding (58.8% vs. 96.9) and dietary diversity (15.5% vs. 99%) was substantially lower in controls (p < 0.05). Mean knowledge on exclusive breastfeeding (25.17 ± 1.37 vs. 19.87 ± 1.80), complementary feeding (15.68 ± 0.60, vs. 13.51 ± 1.21) and total knowledge scores (46.8 ± 1.79 vs. 38.65 ± 2.71) was higher in the BabyThrive group (p < 0.05). Conclusions: In sum, the BabyThrive app significantly increased maternal IYCF knowledge in comparison with controls. It will be a useful tool to improve maternal IYCF knowledge in resource-limited areas.
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Affiliation(s)
- Mercy E. Sosanya
- Department of Nutritional Sciences, University of Texas at Austin, Austin, TX 78712, USA;
- Department of Nutrition and Dietetics, The Federal Polytechnic, Bauchi, Bauchi 740102, Nigeria; (O.D.A.); (H.E.R.)
| | - Oluwatosin D. Adesanya
- Department of Nutrition and Dietetics, The Federal Polytechnic, Bauchi, Bauchi 740102, Nigeria; (O.D.A.); (H.E.R.)
| | - Hauwa E. Rufai
- Department of Nutrition and Dietetics, The Federal Polytechnic, Bauchi, Bauchi 740102, Nigeria; (O.D.A.); (H.E.R.)
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Burke RM, Ramani S, Lynch J, Cooper LV, Cho H, Bandyopadhyay AS, Kirkwood CD, Steele AD, Kang G. Geographic disparities impacting oral vaccine performance: Observations and future directions. Clin Exp Immunol 2025; 219:uxae124. [PMID: 39774633 PMCID: PMC11773816 DOI: 10.1093/cei/uxae124] [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: 08/30/2024] [Revised: 11/01/2024] [Accepted: 01/06/2025] [Indexed: 01/11/2025] Open
Abstract
Oral vaccines have several advantages compared with parenteral administration: they can be relatively cheap to produce in high quantities, easier to administer, and induce intestinal mucosal immunity that can protect against infection. These characteristics have led to successful use of oral vaccines against rotavirus, polio, and cholera. Unfortunately, oral vaccines for all three diseases have demonstrated lower performance in the highest-burden settings where they are most needed. Rotavirus vaccines are estimated to have >85% effectiveness against hospitalization in children <12 months in countries with low child mortality, but only ~65% effectiveness in countries with high child mortality. Similarly, oral polio vaccines have lower immunogenicity in developing country settings compared with high-resource settings. Data are more limited for oral cholera vaccines, but suggest lower titers among children compared with adults, and, for some vaccines, lower efficacy in endemic settings compared with non-endemic settings. These disparities are likely multifactorial, and available evidence suggests a role for maternal factors (e.g. transplacental antibodies, breastmilk), host factors (e.g. genetic polymorphisms-with the best evidence for rotavirus-or previous infection), and environmental factors (e.g. gut microbiome, co-infections). Overall, these data highlight the rather ambiguous and often contradictory nature of evidence on factors affecting oral vaccine response, cautioning against broad extrapolation of outcomes based on one population or one vaccine type. Meaningful impact on performance of oral vaccines will likely only be possible with a suite of interventions, given the complex and multifactorial nature of the problem, and the degree to which contributing factors are intertwined.
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Affiliation(s)
- Rachel M Burke
- Global Development Division, Bill & Melinda Gates Foundation, Seattle, WA, USA
| | - Sasirekha Ramani
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Julia Lynch
- Office of the Director General, International Vaccine Institute, Seoul, Republic of Korea
| | - Laura V Cooper
- School of Public Health, Imperial College London, London, UK
| | - Haeun Cho
- Department of Data Science and Innovation, International Vaccine Institute, Seoul, Republic of Korea
| | | | - Carl D Kirkwood
- Global Health Division, Bill & Melinda Gates Foundation, Seattle, WA, USA
| | - A Duncan Steele
- Global Health Division, Bill & Melinda Gates Foundation, Seattle, WA, USA
| | - Gagandeep Kang
- Global Health Division, Bill & Melinda Gates Foundation, Seattle, WA, USA
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Zhou W, Tang J. Prevalence and risk factors for childhood asthma: a systematic review and meta-analysis. BMC Pediatr 2025; 25:50. [PMID: 39833735 PMCID: PMC11744885 DOI: 10.1186/s12887-025-05409-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 01/07/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND This study aimed to systematically review and perform a meta-analysis on epidemiological studies in order to estimate the global and regional prevalence and to identify risk factors associated with childhood asthma. METHODS A comprehensive search of the PubMed, Embase, and Cochrane Library electronic databases was conducted for relevant literature published from their inception to March 31, 2023. The primary endpoint was the prevalence of childhood asthma. Secondary endpoint focused on the identification of risk factors associated with childhood asthma. RESULTS A total of 1,547,404 children participated in the 164 studies selected for the meta-analysis. The overall prevalence of childhood asthma was 10.2% (95% CI: 9.5-11.0%), while the prevalence of childhood asthma in Asia, Europe, Latin America, North America, Oceania, Africa, or Eurasia were 10% (95%CI: 7-13%), 9% (95%CI: 7-12%), 14% (95%CI: 9-20%), 13% (95%CI: 12-14%), 23% (95%CI: 19-28%), 11% (95%CI: 7-19%), and 8% (95%CI: 2-27%), respectively. Moreover, the identified risk factors for childhood asthma included older age, male sex, obesity, parental smoking, high education of the mother, premature birth, cesarean section, no breastfeeding, family history of asthma, rhinitis, eczema, pets, high density of road traffic, meat, margarine, fast food, paracetamol use, and antibiotic use. CONCLUSION Childhood asthma is common, and the prevalence of asthma is highest in Oceania, with a lower prevalence in Eurasia. Moreover, the risk factors for childhood asthma were comprehensively identified, and health education should be provided to prevent modifiable factors.
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Affiliation(s)
- Weijun Zhou
- Department of Pediatrics, Chongqing Yubei District People's Hospital, Jianshe Road, Chongqing401120, China.
| | - Jia Tang
- Department of Pediatrics, Chongqing Yubei District People's Hospital, Jianshe Road, Chongqing401120, China
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Fricker AD, Sejane K, Desai M, Snyder MW, Duran L, Mackelprang R, Bode L, Ross MG, Flores GE. A Pilot Study Exploring the Relationship Between Milk Composition and Microbial Capacity in Breastfed Infants. Nutrients 2025; 17:338. [PMID: 39861468 PMCID: PMC11768495 DOI: 10.3390/nu17020338] [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: 12/13/2024] [Revised: 01/10/2025] [Accepted: 01/14/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Maternal obesity may contribute to childhood obesity in a myriad of ways, including through alterations of the infant gut microbiome. For example, maternal obesity may contribute both directly by introducing a dysbiotic microbiome to the infant and indirectly through the altered composition of human milk that fuels the infant gut microbiome. In particular, indigestible human milk oligosaccharides (HMOs) are known to shape the composition of the infant gut microbiome. The goal of this study was to characterize the HMO profiles of normal-weight and overweight mothers and to quantitatively link HMO concentrations to the taxonomic composition and functional potential of the infant gut microbiome. METHODS Normal-weight (BMI = 18.5-24.9; n = 9) and overweight/obese (OW/OB; BMI > 25; n = 11) breastfeeding mothers and their infants were enrolled in this single-center, cross-sectional pilot study. Human milk from the mothers and rectal stool swabs from the infants were collected 7-9 weeks postpartum. The HMO composition, microbiome composition, and microbial functions were assessed using HPLC, 16S rRNA gene sequencing, and metagenomic sequencing, respectively. RESULTS Neither the HMO profiles nor the infant microbiome composition varied according to maternal BMI status. Taxonomically, the gut microbiota of infants were dominated by typical gut lineages including Bifidobacterium. Significant correlations between individual HMOs and bacterial genera were identified, including for Prevotella, a genus of the Bacteroidota phylum that was positively correlated with the concentrations of lacto-N-neotetraose (LNnT) and lacto-N-hexaose (LNH). Using metagenomic assembled genomes, we were also able to identify the broad HMO-degradative capacity across the Bifidobacterium and Prevotella genera. CONCLUSIONS These results suggest that the maternal BMI status does not impact the HMO profiles of human milk. However, select HMOs were correlated with specific bacterial taxa, suggesting that the milk composition influences both the taxonomic composition and the functional capacity of the infant gut microbiome.
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Affiliation(s)
- Ashwana D. Fricker
- Department of Biology, California State University, Northridge, CA 91330, USA; (A.D.F.)
- Biology Department, Adelphi University, Garden City, NY 11530, USA
| | - Kristija Sejane
- Department of Pediatrics, Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), and the Human Milk Institute (HMI), University of California San Diego, La Jolla, CA 92093, USA (L.B.)
| | - Mina Desai
- The Lundquist Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA 90502, USA;
- Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles at Harbor-UCLA, Torrance, CA 90502, USA
| | - Michael W. Snyder
- Department of Biology, California State University, Northridge, CA 91330, USA; (A.D.F.)
| | - Luis Duran
- Department of Biology, California State University, Northridge, CA 91330, USA; (A.D.F.)
| | - Rachel Mackelprang
- Department of Biology, California State University, Northridge, CA 91330, USA; (A.D.F.)
| | - Lars Bode
- Department of Pediatrics, Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), and the Human Milk Institute (HMI), University of California San Diego, La Jolla, CA 92093, USA (L.B.)
| | - Michael G. Ross
- The Lundquist Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA 90502, USA;
- Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles at Harbor-UCLA, Torrance, CA 90502, USA
- Department of Obstetrics and Gynecology, Charles R. Drew University, Los Angeles, CA 90059, USA
| | - Gilberto E. Flores
- Department of Biology, California State University, Northridge, CA 91330, USA; (A.D.F.)
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Castro-Navarro I, Pace RM, Williams JE, Pace CDW, Kaur H, Piaskowski J, Aragón A, Rodríguez JM, McGuire MA, Fernandez L, McGuire MK. Immunological composition of human milk before and during subclinical and clinical mastitis. Front Immunol 2025; 15:1532432. [PMID: 39896819 PMCID: PMC11782115 DOI: 10.3389/fimmu.2024.1532432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 12/30/2024] [Indexed: 02/04/2025] Open
Abstract
Mastitis, an inflammatory condition affecting more than 25% of breastfeeding women, is usually associated with reduced milk secretion, pain, and discomfort, which often leads to early cessation of breastfeeding. Although the etiology of mastitis is multifactorial, a pro-inflammatory state of the mammary gland might be a risk factor. However, changes in milk composition, and specifically in the milk immune profile, prior to and during mastitis have not been well described. To help close this research gap, we documented the immune profiles of milk produced by both breasts of 10 women experiencing clinical (CM) and 8 women experiencing subclinical (SCM) mastitis during the week of sign/symptom development as well as the week prior and compared them with milk produced by 14 healthy controls. CM was defined as having signs/symptoms of mastitis, whereas SCM was presumed if the participant did not have signs/symptoms of CM, but her milk had a somatic cell count >400,000 cell/mL and/or sodium-to-potassium (Na/K) ratio >1.0. Concentration of 36 immune factors (including immunoglobulins, cytokines, chemokines, and growth factors) was quantified via immunoassays. Milk produced by women who developed CM had distinct immune profiles the week prior to diagnosis, particularly elevated concentrations of pro-inflammatory cytokine IL-1β and regulatory cytokines IL-2, IL-4 and IL-10. In contrast, immune profiles in milk produced by women with SCM did not differ from that produced by healthy women or those with CM the week prior to mastitis onset. Once mastitis appeared, marked changes in milk's immune profile were observed in both CM and SCM groups. CM was characterized by elevated concentrations of 27 compounds, including pro-inflammatory cytokines (IL-1β, IL-1ra, and TNFα) and chemokines (including IL-8, eotaxin, IP-10, MCP-1, MIP1α, and MIP1β), compared to healthy controls. Milk's immune profile during SCM was intermediate, showing higher levels of IL-6, IFNγ, and MCP-1 compared to healthy controls, suggesting a milder, more controlled immune response compared to CM. Only milk produced by the mastitis-affected breast had altered immune profiles. Further research is needed to determine if these differences in milk's immune profiles can be used to improve mastitis risk prediction prior to onset of symptoms.
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Affiliation(s)
- Irma Castro-Navarro
- Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID, United States
| | - Ryan M. Pace
- Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID, United States
- College of Nursing, University of South Florida, Tampa, FL, United States
- Microbiomes Institute, University of South Florida, Tampa, FL, United States
| | - Janet E. Williams
- Department of Animal, Veterinary and Food Sciences, University of Idaho, Moscow, ID, United States
| | - Christina D. W. Pace
- Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID, United States
| | - Harpreet Kaur
- Statistical Programs, College of Agricultural and Life Sciences, University of Idaho, Moscow, ID, United States
| | - Julia Piaskowski
- Statistical Programs, College of Agricultural and Life Sciences, University of Idaho, Moscow, ID, United States
| | - Alberto Aragón
- Department of Galenic Pharmacy and Food Technology, Complutense University of Madrid, Madrid, Spain
- Instituto Pluridisciplinar, Complutense University of Madrid, Madrid, Spain
| | - Juan M. Rodríguez
- Instituto Pluridisciplinar, Complutense University of Madrid, Madrid, Spain
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
| | - Mark A. McGuire
- Department of Animal, Veterinary and Food Sciences, University of Idaho, Moscow, ID, United States
| | - Leonides Fernandez
- Department of Galenic Pharmacy and Food Technology, Complutense University of Madrid, Madrid, Spain
- Instituto Pluridisciplinar, Complutense University of Madrid, Madrid, Spain
| | - Michelle K. McGuire
- Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID, United States
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50
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Silpe JE, Damian-Medina K, Bassler BL. Food-Derived Compounds Extend the Shelf-Life of Frozen Human Milk. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2024.12.11.627965. [PMID: 39713284 PMCID: PMC11661246 DOI: 10.1101/2024.12.11.627965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/24/2024]
Abstract
Breastmilk is known to provide optimal nutrition for infant growth and development. A cross-sectional analysis of nationally representative US data from 2016 to 2021 revealed that >90% of lactating mothers reported using breast pumps to express milk.1 We conducted a survey of n = 1,049 lactating or recently lactating individuals from a US nationally representative population to explore breastmilk storage practices among this group. The data revealed that 83% of respondents store breastmilk in their homes, with 68% using freezers to do so for >1 month. The lowest available temperature in most household freezers is -20 °C, a temperature that is inadequate to maintain human milk's emulsified structure, leading to separation, degradation of fats, loss of key vitamins, and changes in palatability. We developed a first-of-its-kind high-throughput screening platform to identify food-derived compounds and combinations of compounds that, when added to human breastmilk, preserve fat content, retain antioxidant capacity, and reduce production of rancid-associated free fatty acids during extended freezer storage. These formulations represent leads for the development of safe and affordable frozen breastmilk shelf-life extenders for easy at-home use to increase the longevity of stored breastmilk.
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Affiliation(s)
- Justin E. Silpe
- Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA
- Howard Hughes Medical Institute, Chevy Chase, Maryland, USA
- PumpKin Baby Inc., Princeton, New Jersey, USA
| | | | - Bonnie L. Bassler
- Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA
- Howard Hughes Medical Institute, Chevy Chase, Maryland, USA
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