|
1
|
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.
Collapse
Affiliation(s)
- Mohammed Al-Beltagi
- Department of Paediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| |
Collapse
|
|
2
|
Froń A, Orczyk-Pawiłowicz M. Breastfeeding Beyond Six Months: Evidence of Child Health Benefits. Nutrients 2024; 16:3891. [PMID: 39599677 PMCID: PMC11597163 DOI: 10.3390/nu16223891] [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: 09/30/2024] [Revised: 11/05/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024] Open
Abstract
Breastfeeding is globally recognized as the optimal method of infant nutrition, offering health benefits for both the child and the mother, making it a public health priority. However, the potential advantages of breastfeeding extend well beyond initial months. Breast milk adapts to the evolving needs of the growing infant, and its immunological, microbiological, and biochemical properties have been associated with enhanced protection against infections and chronic diseases, improved growth and development, and lower rates of hospitalization and mortality. This review explores the evidence supporting the continuation of breastfeeding beyond six months. More meticulous studies employing consistent methodologies and addressing confounders are essential. This will enable a more accurate determination of the extent and mechanisms of the positive impact of prolonged breastfeeding and allow for the implementation of effective public health strategies.
Collapse
Affiliation(s)
- Anita Froń
- Division of Chemistry and Immunochemistry, Department of Biochemistry and Immunochemistry, Wroclaw Medical University, M. Skłodowskiej-Curie 48/50, 50-369 Wroclaw, Poland;
| | | |
Collapse
|
|
3
|
Malloy MH. Armond S. Goldman (1930-2023) and the development of the immunobiology of human milk. JOURNAL OF MEDICAL BIOGRAPHY 2024:9677720241280762. [PMID: 39300816 DOI: 10.1177/09677720241280762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/22/2024]
Abstract
The understanding of the immunobiology of human milk is primarily a 20th-century phenomenon, but, even with our contemporary understanding, it remains a bit of a mystery. Breastfeeding of human milk, although the most obvious and natural form of nutrition for human infants, has been hindered by cultural and societal norms since ancient times. Thus, not all infants have experienced the advantages this form of nutrition may offer. Although these advantages have been anecdotally suggested since ancient times, it was only in the late 19th and early 20th centuries that the superiority of human milk was scientifically documented. The underlying immunobiological properties of human milk underpinning its observed superiority only became appreciated with advances in immunology that occurred in the mid to late 20th century. Armond S. Goldman (1930-2023) was in the vanguard of those promoting and developing an understanding of the immunobiology of human milk and its superiority in promoting the health of human infants.
Collapse
Affiliation(s)
- Michael H Malloy
- Emeritus John P. McGovern Chair in Oslerian Education, The University of Texas Medical Branch, Galveston, TX, USA
| |
Collapse
|
|
4
|
Cheifetz TR, Knoop KA. The right educational environment: Oral tolerance in early life. Immunol Rev 2024; 326:17-34. [PMID: 39001685 PMCID: PMC11436309 DOI: 10.1111/imr.13366] [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] [Indexed: 09/28/2024]
Abstract
Oral tolerance promotes the suppression of immune responses to innocuous antigen and is primarily mediated by regulatory T cell (Tregs). The development of oral tolerance begins in early life during a "window of tolerance," which occurs around weaning and is mediated by components in breastmilk. Herein, we review the factors dictating this window and how Tregs are uniquely educated in early life. In early life, the translocation of luminal antigen for Treg induction is primarily dictated by goblet cell-associated antigen passages (GAPs). GAPs in the colon are negatively regulated by maternally-derived epidermal growth factor and the microbiota, restricting GAP formation to the "periweaning" period (postnatal day 11-21 in mice, 4-6 months in humans). The induction of solid food also promotes the diversification of the bacteria such that bacterially-derived metabolites known to promote Tregs-short-chain fatty acids, tryptophan metabolites, and bile acids-peak during the periweaning phase. Further, breastmilk immunoglobulins-IgA and IgG-regulate both microbial diversity and the interaction of microbes with the epithelium, further controlling which antigens are presented to T cells. Overall, these elements work in conjunction to induce a long-lived population of Tregs, around weaning, that are crucial for maintaining homeostasis in adults.
Collapse
Affiliation(s)
- Talia R. Cheifetz
- Department of Immunology, Mayo Clinic, Rochester MN
- Mayo Graduate School of Biomedical Sciences, Rochester MN
| | - Kathryn A. Knoop
- Department of Immunology, Mayo Clinic, Rochester MN
- Department of Pediatrics, Mayo Clinic, Rochester MN
| |
Collapse
|
|
5
|
Fernández-Buhigas I, Rayo N, Silos JC, Serrano B, Ocón-Hernández O, Leung BW, Delgado JL, Fernández DSN, Valle S, De Miguel L, Silgado A, Tanoira RP, Rolle V, Santacruz B, Gil MM, Poon LC. Anti-SARS-CoV-2-specific antibodies in human breast milk following SARS-CoV-2 infection during pregnancy: a prospective cohort study. Int Breastfeed J 2024; 19:5. [PMID: 38238855 PMCID: PMC10797875 DOI: 10.1186/s13006-023-00605-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 12/02/2023] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND While the presence of SARS-CoV-2 in human breast milk is contentious, anti-SARS-CoV-2 antibodies have been consistently detected in human breast milk. However, it is uncertain when and how long the antibodies are present. METHODS This was a prospective cohort study including all consecutive pregnant women with confirmed SARS-CoV-2 infection during pregnancy, recruited at six maternity units in Spain and Hong Kong from March 2020 to March 2021. Colostrum (day of birth until day 4 postpartum) and mature milk (day 7 postpartum until 6 weeks postpartum) were prospectively collected, and paired maternal blood samples were also collected. Colostrum samples were tested with rRT-PCR-SARS-CoV-2, and skimmed acellular milk and maternal sera were tested against SARS-CoV-2 specific immunoglobulin M, A, and G reactive to receptor binding domain of SARS-CoV-2 spike protein 1 to determine the presence of immunoglobulins. Then, we examined how each immunoglobulin type in the colostrum was related to the time of infection by logistic regression analysis, the concordance between these immunoglobulins in the colostrum, maternal serum, and mature milk by Cohen's kappa statistic, and the relationship between immunoglobulin levels in mature milk and colostrum with McNemar. RESULTS One hundred eighty-seven pregnant women with confirmed SARS-CoV-2 infection during pregnancy or childbirth were recruited and donated the milk and blood samples. No SARS-CoV-2 was found in the human breast milk. Immunoglobulin A, G, and M were present in 129/162 (79·6%), 5/163 (3·1%), and 15/76 (19·7%) colostrum samples and in 17/62 (27·42%), 2/62 (3·23%) and 2/62 (3·23%) mature milk samples, respectively. Immunoglobulin A was the predominant immunoglobulin found in breast milk, and its levels were significantly higher in the colostrum than in the mature milk (p-value < 0.001). We did not find that the presence of immunoglobulins in the colostrum was associated with their presence in maternal, the severity of the disease, or the time when the infection had occurred. CONCLUSIONS Since anti-SARS-CoV-2 antibodies are found in the colostrum irrespective of the time of infection during pregnancy, but the virus itself is not detected in human breast milk, our study found no indications to withhold breastfeeding, taking contact precautions when there is active disease.
Collapse
Affiliation(s)
- Irene Fernández-Buhigas
- Obstetrics and Gynecology Department, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain
- Vicerrectorado de Investigación, Facultad de Medicina, Universidad Francisco de Vitoria, Carretera Pozuelo a Majadahonda, Km 1.800, Pozuelo de Alarcón, Madrid, 28223, Spain
| | - Nieves Rayo
- Obstetrics and Gynecology Department, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain
- Vicerrectorado de Investigación, Facultad de Medicina, Universidad Francisco de Vitoria, Carretera Pozuelo a Majadahonda, Km 1.800, Pozuelo de Alarcón, Madrid, 28223, Spain
| | - Julia Cuesta Silos
- Synlab Diagnósticos Globales S.A., Esplugues de Llobregat, Catalonia, Spain
| | - Berta Serrano
- Department of Obstetrics, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
| | - Olga Ocón-Hernández
- Obstetrics and Gynecology Department, Hospital Universitario Clínico San Cecilio, Granada, Spain
- Instituto de Investigación Biosanitaria Ibs, Granada, Spain
| | - Bo Wah Leung
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Juan Luis Delgado
- Obstetrics and Gynecology Department, Hospital Clínico Universitario Virgen de La Arrixaca, El Palmar, Murcia, Spain
| | - David Sánchez-Nieves Fernández
- Obstetrics and Gynecology Department, Hospital Universitário Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
- Universidad de Alcalá de Henares, School of Medicine, Alcalá de Henares, Madrid, Spain
| | - Silvia Valle
- Obstetrics and Gynecology Department, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain
- Vicerrectorado de Investigación, Facultad de Medicina, Universidad Francisco de Vitoria, Carretera Pozuelo a Majadahonda, Km 1.800, Pozuelo de Alarcón, Madrid, 28223, Spain
| | - Laura De Miguel
- Synlab Diagnósticos Globales S.A., Esplugues de Llobregat, Catalonia, Spain
| | - Aroa Silgado
- Department of Microbiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
| | - Ramón Perez Tanoira
- Department of Microbiology, Hospital Universitário Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
| | - Valeria Rolle
- Biostatistics and Epidemiology Platform at Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Asturias, Spain
| | - Belén Santacruz
- Obstetrics and Gynecology Department, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain
- Vicerrectorado de Investigación, Facultad de Medicina, Universidad Francisco de Vitoria, Carretera Pozuelo a Majadahonda, Km 1.800, Pozuelo de Alarcón, Madrid, 28223, Spain
| | - Maria M Gil
- Obstetrics and Gynecology Department, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain.
- Vicerrectorado de Investigación, Facultad de Medicina, Universidad Francisco de Vitoria, Carretera Pozuelo a Majadahonda, Km 1.800, Pozuelo de Alarcón, Madrid, 28223, Spain.
| | - Liona C Poon
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China.
| |
Collapse
|
|
6
|
Armistead B, Jiang Y, Carlson M, Ford ES, Jani S, Houck J, Wu X, Jing L, Pecor T, Kachikis A, Yeung W, Nguyen T, Coig R, Minkah N, Larsen SE, Coler RN, Koelle DM, Harrington WE. Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination. Mucosal Immunol 2023; 16:39-49. [PMID: 36642379 PMCID: PMC9836998 DOI: 10.1016/j.mucimm.2023.01.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/20/2022] [Accepted: 01/07/2023] [Indexed: 01/15/2023]
Abstract
Human breastmilk is rich in T cells; however, their specificity and function are largely unknown. We compared the phenotype, diversity, and antigen specificity of T cells in breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 messenger RNA (mRNA) vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor sequence overlap was limited between blood and breastmilk. Overabundant breastmilk clones were observed in all individuals, were diverse, and contained complementarity-determining regions in three sequences with known epitope specificity, including to SARS-CoV-2 spike. SARS-CoV-2 spike-specific T cell receptors were more frequent in breastmilk compared to blood and expanded in breastmilk following a 3rd mRNA vaccine dose. Our observations indicate that the lactating breast contains a distinct T cell population that can be modulated by maternal vaccination with potential implications for passive infant protection.
Collapse
Affiliation(s)
- Blair Armistead
- Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA
| | - Yonghou Jiang
- Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA
| | - Marc Carlson
- Research Scientific Computing, Enterprise Analytics, Seattle Children's Research Institute, Seattle, Washington, USA
| | - Emily S Ford
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Saumya Jani
- Department of Medicine, University of Washington, Seattle, Washington, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, Washington, USA
| | - John Houck
- Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA
| | - Xia Wu
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Lichen Jing
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Tiffany Pecor
- Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA
| | - Alisa Kachikis
- Department of Obstetrics & Gynecology, University of Washington, Seattle, Washington, USA
| | - Winnie Yeung
- Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA
| | - Tina Nguyen
- Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA
| | - Rene Coig
- Department of Laboratory Medicine & Pathology, University of Washington, Seattle, Washington, USA
| | - Nana Minkah
- Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA; Department of Pediatrics, University of Washington, Seattle, Washington, USA
| | - Sasha E Larsen
- Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA
| | - Rhea N Coler
- Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA; Department of Pediatrics, University of Washington, Seattle, Washington, USA; Department of Global Health, University of Washington, Seattle, Washington, USA
| | - David M Koelle
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, Washington, USA; Department of Global Health, University of Washington, Seattle, Washington, USA; Benaroya Research Institute, Seattle, Washington, USA
| | - Whitney E Harrington
- Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA; Department of Pediatrics, University of Washington, Seattle, Washington, USA; Department of Global Health, University of Washington, Seattle, Washington, USA.
| |
Collapse
|
|
7
|
Armistead B, Jiang Y, Carlson M, Ford ES, Jani S, Houck J, Wu X, Jing L, Pecor T, Kachikis A, Yeung W, Nguyen T, Minkah N, Larsen SE, Coler RN, Koelle DM, Harrington WE. Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2022:2021.12.03.21267036. [PMID: 36203549 PMCID: PMC9536058 DOI: 10.1101/2021.12.03.21267036] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Human breastmilk is rich in T cells; however, their specificity and function are largely unknown. We compared the phenotype, diversity, and antigen specificity of T cells in the breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 mRNA vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor (TCR) sequence overlap was limited between blood and breastmilk. Overabundan t breastmilk clones were observed in all individuals, were diverse, and contained CDR3 sequences with known epitope specificity including to SARS-CoV-2 Spike. Spike-specific TCRs were more frequent in breastmilk compared to blood and expanded in breastmilk following a third mRNA vaccine dose. Our observations indicate that the lactating breast contains a distinct T cell population that can be modulated by maternal vaccination with potential implications for infant passive protection. One-Sentence Summary The breastmilk T cell repertoire is distinct and enriched for SARS-CoV-2 Spike-specificity after maternal mRNA vaccination.
Collapse
Affiliation(s)
- Blair Armistead
- Center for Global Infectious Disease Research, Seattle Children’s Research Institute; Seattle, WA, USA
| | - Yonghou Jiang
- Center for Global Infectious Disease Research, Seattle Children’s Research Institute; Seattle, WA, USA
| | - Marc Carlson
- Research Scientific Computing, Enterprise Analytics, Seattle Children’s Research Institute; Seattle, WA, USA
| | - Emily S Ford
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center; Seattle, WA, USA
- Department of Medicine, University of Washington; Seattle, WA, USA
| | - Saumya Jani
- Department of Medicine, University of Washington; Seattle, WA, USA
- Department of Laboratory Medicine & Pathology, University of Washington; Seattle, WA, USA
| | - John Houck
- Center for Global Infectious Disease Research, Seattle Children’s Research Institute; Seattle, WA, USA
| | - Xia Wu
- Department of Medicine, University of Washington; Seattle, WA, USA
| | - Lichen Jing
- Department of Medicine, University of Washington; Seattle, WA, USA
| | - Tiffany Pecor
- Center for Global Infectious Disease Research, Seattle Children’s Research Institute; Seattle, WA, USA
| | - Alisa Kachikis
- Department of Obstetrics & Gynecology, University of Washington; Seattle, WA, USA
| | - Winnie Yeung
- Center for Global Infectious Disease Research, Seattle Children’s Research Institute; Seattle, WA, USA
| | - Tina Nguyen
- Center for Global Infectious Disease Research, Seattle Children’s Research Institute; Seattle, WA, USA
| | - Nana Minkah
- Center for Global Infectious Disease Research, Seattle Children’s Research Institute; Seattle, WA, USA
- Department of Pediatrics, University of Washington; Seattle, WA, USA
| | - Sasha E Larsen
- Center for Global Infectious Disease Research, Seattle Children’s Research Institute; Seattle, WA, USA
| | - Rhea N Coler
- Center for Global Infectious Disease Research, Seattle Children’s Research Institute; Seattle, WA, USA
- Department of Global Health, University of Washington; Seattle, WA, USA
- Department of Pediatrics, University of Washington; Seattle, WA, USA
| | - David M Koelle
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center; Seattle, WA, USA
- Department of Medicine, University of Washington; Seattle, WA, USA
- Department of Laboratory Medicine & Pathology, University of Washington; Seattle, WA, USA
- Department of Global Health, University of Washington; Seattle, WA, USA
- Benaroya Research Institute; Seattle, WA, USA
| | - Whitney E Harrington
- Center for Global Infectious Disease Research, Seattle Children’s Research Institute; Seattle, WA, USA
- Department of Global Health, University of Washington; Seattle, WA, USA
- Department of Pediatrics, University of Washington; Seattle, WA, USA
| |
Collapse
|
|
8
|
Ruan H, Tang Q, Zhao X, Zhang Y, Zhao X, Xiang Y, Geng W, Feng Y, Cai W. The levels of osteopontin in human milk of Chinese mothers and its associations with maternal body composition. FOOD SCIENCE AND HUMAN WELLNESS 2022. [DOI: 10.1016/j.fshw.2022.04.033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
|
|
9
|
Murrieta-Coxca JM, Fuentes-Zacarias P, Ospina-Prieto S, Markert UR, Morales-Prieto DM. Synergies of Extracellular Vesicles and Microchimerism in Promoting Immunotolerance During Pregnancy. Front Immunol 2022; 13:837281. [PMID: 35844513 PMCID: PMC9285877 DOI: 10.3389/fimmu.2022.837281] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 05/16/2022] [Indexed: 11/13/2022] Open
Abstract
The concept of biological identity has been traditionally a central issue in immunology. The assumption that entities foreign to a specific organism should be rejected by its immune system, while self-entities do not trigger an immune response is challenged by the expanded immunotolerance observed in pregnancy. To explain this "immunological paradox", as it was first called by Sir Peter Medawar, several mechanisms have been described in the last decades. Among them, the intentional transfer and retention of small amounts of cells between a mother and her child have gained back attention. These microchimeric cells contribute to expanding allotolerance in both organisms and enhancing genetic fitness, but they could also provoke aberrant alloimmune activation. Understanding the mechanisms used by microchimeric cells to exert their function in pregnancy has proven to be challenging as per definition they are extremely rare. Profiting from studies in the field of transplantation and cancer research, a synergistic effect of microchimerism and cellular communication based on the secretion of extracellular vesicles (EVs) has begun to be unveiled. EVs are already known to play a pivotal role in feto-maternal tolerance by transferring cargo from fetal to maternal immune cells to reshape their function. A further aspect of EVs is their function in antigen presentation either directly or on the surface of recipient cells. Here, we review the current understanding of microchimerism in the feto-maternal tolerance during human pregnancy and the potential role of EVs in mediating the allorecognition and tropism of microchimeric cells.
Collapse
Affiliation(s)
| | | | | | - Udo R. Markert
- Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany
| | | |
Collapse
|
|
10
|
Balle C, Armistead B, Kiravu A, Song X, Happel AU, Hoffmann AA, Kanaan SB, Nelson JL, Gray CM, Jaspan HB, Harrington WE. Factors influencing maternal microchimerism throughout infancy and its impact on infant T cell immunity. J Clin Invest 2022; 132:e148826. [PMID: 35550376 PMCID: PMC9246390 DOI: 10.1172/jci148826] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/10/2022] [Indexed: 11/17/2022] Open
Abstract
Determinants of the acquisition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors that influence MMc detection and level across infancy and the effect of MMc on T cell responses to bacillus Calmette-Guérin (BCG) vaccination in a cohort of HIV-exposed, uninfected and HIV-unexposed infants in South Africa. MMc was measured in whole blood from 58 infants using a panel of quantitative PCR assays at day 1, and 7, 15, and 36 weeks of life. Infants received BCG at birth, and selected whole blood samples from infancy were stimulated in vitro with BCG and assessed for polyfunctional CD4+ T cell responses. MMc was present in most infants across infancy, with levels ranging from 0 to 1,193/100,000 genomic equivalents and was positively impacted by absence of maternal HIV, maternal and infant HLA compatibility, infant female sex, and exclusive breastfeeding. Initiation of maternal antiretroviral therapy prior to pregnancy partially restored MMc level in HIV-exposed, uninfected infants. Birth MMc was associated with an improved polyfunctional CD4+ T cell response to BCG. These data emphasize that both maternal and infant factors influence the level of MMc, which may subsequently affect infant T cell responses.
Collapse
Affiliation(s)
- Christina Balle
- Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Blair Armistead
- Seattle Children’s Research Institute, Seattle, Washington, USA
| | - Agano Kiravu
- Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Xiaochang Song
- Seattle Children’s Research Institute, Seattle, Washington, USA
- University of Washington School of Medicine, Seattle, Washington, USA
| | - Anna-Ursula Happel
- Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Angela A. Hoffmann
- Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Sami B. Kanaan
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - J. Lee Nelson
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Clive M. Gray
- Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Heather B. Jaspan
- Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Seattle Children’s Research Institute, Seattle, Washington, USA
- Department of Pediatrics and
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | - Whitney E. Harrington
- Seattle Children’s Research Institute, Seattle, Washington, USA
- Department of Pediatrics and
| |
Collapse
|
|
11
|
Laguila Altoé A, Marques Mambriz AP, Cardozo DM, Valentini Zacarias JM, Laguila Visentainer JE, Bahls-Pinto LD. Vaccine Protection Through Placenta and Breastfeeding: The Unmet Topic in COVID-19 Pandemic. Front Immunol 2022; 13:910138. [PMID: 35720385 PMCID: PMC9203883 DOI: 10.3389/fimmu.2022.910138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/09/2022] [Indexed: 01/10/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has turned pregnant women's healthcare into a worldwide public health challenge. Although initial data did not demonstrate pregnancy as a more susceptible period to severe outcomes of acute severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection, there are an increasing number of reports showing that not only pregnant women might be at significantly higher risk than non-pregnant women by COVID-19 but also the fetus. These findings may be related to adaptive changes that occur during pregnancy, such as the reduction in the residual respiratory capacity, the decrease in viral immune responses, and the increased risk for thromboembolic events. Additionally, despite the SARS-CoV-2 vertical transmission evidence being uncommon, maternal illness severity might reflect serious perinatal and neonatal outcomes. Thus, protecting the maternal-fetal dyad against COVID-19 is critical. Even though pregnant women initially were excluded from vaccine trials, several studies have provided safety and efficacy of the overall vaccine COVID-19 platforms. Vaccination during pregnancy becomes a priority and can generate benefits for both the mother and newborn: maternal neutralizing antibodies are transmitted through the placenta and breastfeeding. Moreover, regarding passive immunization, human milk contains other bioactive molecules and cells able to modulate the newborn's immune response, which can be amplified after the vaccine. Nonetheless, many issues remain to be elucidated, considering the magnitude of the protective immunity transferred, the duration of the induced immunity, and the optimal interval for pregnant immunization. In this review, we assessed these unmet topics supported by literature evidence regarding the vaccine's immunogenicity, pregnancy immune heterogeneity, and the unique human milk antiviral features.
Collapse
Affiliation(s)
- Ariane Laguila Altoé
- Department of Basic Health Science, Laboratory of Immunogenetics, State University of Maringa, Maringa, Brazil
- Department of Medicine, State University of Maringa, Maringa, Brazil
| | - Anna Paula Marques Mambriz
- Department of Clinical Analysis and Biomedicine, Postgraduate Program in Biosciences and Physiopathology, State University of Maringa, Maringa, Brazil
| | | | - Joana Maira Valentini Zacarias
- Department of Basic Health Science, Laboratory of Immunogenetics, State University of Maringa, Maringa, Brazil
- Department of Clinical Analysis and Biomedicine, Postgraduate Program in Biosciences and Physiopathology, State University of Maringa, Maringa, Brazil
| | - Jeane Eliete Laguila Visentainer
- Department of Basic Health Science, Laboratory of Immunogenetics, State University of Maringa, Maringa, Brazil
- Department of Clinical Analysis and Biomedicine, Postgraduate Program in Biosciences and Physiopathology, State University of Maringa, Maringa, Brazil
| | | |
Collapse
|
|
12
|
Hatmal MM, Al-Hatamleh MAI, Olaimat AN, Alshaer W, Hasan H, Albakri KA, Alkhafaji E, Issa NN, Al-Holy MA, Abderrahman SM, Abdallah AM, Mohamud R. Immunomodulatory Properties of Human Breast Milk: MicroRNA Contents and Potential Epigenetic Effects. Biomedicines 2022; 10:1219. [PMID: 35740242 PMCID: PMC9219990 DOI: 10.3390/biomedicines10061219] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 05/15/2022] [Accepted: 05/17/2022] [Indexed: 02/07/2023] Open
Abstract
Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant's early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors.
Collapse
Affiliation(s)
- Ma’mon M. Hatmal
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Mohammad A. I. Al-Hatamleh
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia;
| | - Amin N. Olaimat
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan; (A.N.O.); (M.A.A.-H.)
| | - Walhan Alshaer
- Cell Therapy Center (CTC), The University of Jordan, Amman 11942, Jordan;
| | - Hanan Hasan
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan;
| | - Khaled A. Albakri
- Faculty of Medicine, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Enas Alkhafaji
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan;
| | - Nada N. Issa
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Murad A. Al-Holy
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan; (A.N.O.); (M.A.A.-H.)
| | - Salim M. Abderrahman
- Department of Biology and Biotechnology, Faculty of Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Atiyeh M. Abdallah
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar;
| | - Rohimah Mohamud
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia;
| |
Collapse
|
|
13
|
Pullen KM, Atyeo C, Collier ARY, Gray KJ, Belfort MB, Lauffenburger DA, Edlow AG, Alter G. Selective functional antibody transfer into the breastmilk after SARS-CoV-2 infection. Cell Rep 2021; 37:109959. [PMID: 34739850 PMCID: PMC8531199 DOI: 10.1016/j.celrep.2021.109959] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 09/16/2021] [Accepted: 10/18/2021] [Indexed: 12/24/2022] Open
Abstract
Antibody transfer via breastmilk represents an evolutionary strategy to boost immunity in early life. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies have been observed in the breastmilk, the functional quality of these antibodies remains unclear. Here, we apply systems serology to characterize SARS-CoV-2-specific antibodies in maternal serum and breastmilk to compare the functional characteristics of antibodies in these fluids. Distinct SARS-CoV-2-specific antibody responses are observed in the serum and breastmilk of lactating individuals previously infected with SARS-CoV-2, with a more dominant transfer of immunoglobulin A (IgA) and IgM into breastmilk. Although IgGs are present in breastmilk, they are functionally attenuated. We observe preferential transfer of antibodies capable of eliciting neutrophil phagocytosis and neutralization compared to other functions, pointing to selective transfer of certain functional antibodies to breastmilk. These data highlight the preferential transfer of SARS-CoV-2-specific IgA and IgM to breastmilk, accompanied by select IgG subpopulations, positioned to create a non-pathologic but protective barrier against coronavirus disease 2019 (COVID-19).
Collapse
Affiliation(s)
- Krista M Pullen
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Caroline Atyeo
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA 02115, USA
| | - Ai-Ris Y Collier
- Department of Obstetrics, Gynecology and Reproductive Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Kathryn J Gray
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Mandy B Belfort
- Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Douglas A Lauffenburger
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Andrea G Edlow
- Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
| | - Galit Alter
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
| |
Collapse
|
|
14
|
Rio-Aige K, Azagra-Boronat I, Castell M, Selma-Royo M, Collado MC, Rodríguez-Lagunas MJ, Pérez-Cano FJ. The Breast Milk Immunoglobulinome. Nutrients 2021; 13:nu13061810. [PMID: 34073540 PMCID: PMC8230140 DOI: 10.3390/nu13061810] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 05/19/2021] [Accepted: 05/23/2021] [Indexed: 12/24/2022] Open
Abstract
Breast milk components contribute to the infant’s immune development and protection, and among other immune factors, immunoglobulins (Igs) are the most studied. The presence of IgA in milk has been known for a long time; however, less information is available about the presence of other Igs such as IgM, IgG, and their subtypes (IgG1, IgG2, IgG3, and IgG4) or even IgE or IgD. The total Ig concentration and profile will change during the course of lactation; however, there is a great variability among studies due to several variables that limit establishing a clear pattern. In this context, the aim of this review was firstly to shed light on the Ig concentration in breast milk based on scientific evidence and secondly to study the main factors contributing to such variability. A search strategy provided only 75 studies with the prespecified eligibility criteria. The concentrations and proportions found have been established based on the intrinsic factors of the study—such as the sampling time and quantification technique—as well as participant-dependent factors, such as lifestyle and environment. All these factors contribute to the variability of the immunoglobulinome described in the literature and should be carefully addressed for further well-designed studies and data interpretation.
Collapse
Affiliation(s)
- Karla Rio-Aige
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (K.R.-A.); (I.A.-B.); (M.C.); (M.J.R.-L.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
| | - Ignasi Azagra-Boronat
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (K.R.-A.); (I.A.-B.); (M.C.); (M.J.R.-L.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
| | - Margarida Castell
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (K.R.-A.); (I.A.-B.); (M.C.); (M.J.R.-L.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
| | - Marta Selma-Royo
- Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), 46890 Paterna, Valencia, Spain; (M.S.-R.); (M.C.C.)
| | - María Carmen Collado
- Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), 46890 Paterna, Valencia, Spain; (M.S.-R.); (M.C.C.)
| | - María J. Rodríguez-Lagunas
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (K.R.-A.); (I.A.-B.); (M.C.); (M.J.R.-L.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
| | - Francisco J. Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (K.R.-A.); (I.A.-B.); (M.C.); (M.J.R.-L.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
- Correspondence: ; Tel.: +34-934-024-505
| |
Collapse
|
|
15
|
Jin D, Liu H, Bu L, Ke Q, Li Z, Han W, Zhu S, Liu C. Comparative Analysis of Whey Proteins in Human Milk Using a Data-Independent Acquisition Proteomics Approach during the Lactation Period. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:4319-4330. [PMID: 33788563 DOI: 10.1021/acs.jafc.1c00186] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Human milk (HM) is the primary source of nutrients and bioactive components that supports the growth and development of infants. However, the proteins present in human milk may change depending on the period of lactation. In this light, the objective of the present study was to evaluate the effect of lactation period on HM utilizing a data-independent acquisition (DIA) approach to identify the differences in HM whey protein proteomes. As part of the study, whey proteins of January, February, and June in human milk were studied. The results identified a total of 1563 proteins in HM whey proteins of which 114 groups were subunits of differentially expressed proteins as revealed by cluster analysis. Protein expression was observed to be affected by the period of lactation with expression levels of plasminogen, thrombospondin-1, and tenascin higher during January, keratin, type I cytoskeletal 9 highest in February, and transcobalamin-1 highest in June. The results of this study contribute to expand our understanding of the human whey proteome but also provide strong evidence for the nutritional difference of HM during different lactation periods.
Collapse
Affiliation(s)
- Dengpeng Jin
- The Key Laboratory of Food Quality and Safety of Guangdong Province, College of Food Science, South China Agricultural University, Guangzhou 510642, China
| | - Huan Liu
- The Key Laboratory of Food Quality and Safety of Guangdong Province, College of Food Science, South China Agricultural University, Guangzhou 510642, China
| | - Lingling Bu
- The Key Laboratory of Food Quality and Safety of Guangdong Province, College of Food Science, South China Agricultural University, Guangzhou 510642, China
| | - Qianhua Ke
- The Key Laboratory of Food Quality and Safety of Guangdong Province, College of Food Science, South China Agricultural University, Guangzhou 510642, China
| | - Zhongyi Li
- The Key Laboratory of Food Quality and Safety of Guangdong Province, College of Food Science, South China Agricultural University, Guangzhou 510642, China
| | - Wenna Han
- The Key Laboratory of Food Quality and Safety of Guangdong Province, College of Food Science, South China Agricultural University, Guangzhou 510642, China
| | - Siyu Zhu
- The Key Laboratory of Food Quality and Safety of Guangdong Province, College of Food Science, South China Agricultural University, Guangzhou 510642, China
| | - Chunhong Liu
- The Key Laboratory of Food Quality and Safety of Guangdong Province, College of Food Science, South China Agricultural University, Guangzhou 510642, China
| |
Collapse
|
|
16
|
Boudry G, Charton E, Le Huerou-Luron I, Ferret-Bernard S, Le Gall S, Even S, Blat S. The Relationship Between Breast Milk Components and the Infant Gut Microbiota. Front Nutr 2021; 8:629740. [PMID: 33829032 PMCID: PMC8019723 DOI: 10.3389/fnut.2021.629740] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 02/16/2021] [Indexed: 12/12/2022] Open
Abstract
The assembly of the newborn's gut microbiota during the first months of life is an orchestrated process resulting in specialized microbial ecosystems in the different gut compartments. This process is highly dependent upon environmental factors, and many evidences suggest that early bacterial gut colonization has long-term consequences on host digestive and immune homeostasis but also metabolism and behavior. The early life period is therefore a "window of opportunity" to program health through microbiota modulation. However, the implementation of this promising strategy requires an in-depth understanding of the mechanisms governing gut microbiota assembly. Breastfeeding has been associated with a healthy microbiota in infants. Human milk is a complex food matrix, with numerous components that potentially influence the infant microbiota composition, either by enhancing specific bacteria growth or by limiting the growth of others. The objective of this review is to describe human milk composition and to discuss the established or purported roles of human milk components upon gut microbiota establishment. Finally, the impact of maternal diet on human milk composition is reviewed to assess how maternal diet could be a simple and efficient approach to shape the infant gut microbiota.
Collapse
Affiliation(s)
- Gaëlle Boudry
- Institut NuMeCan, INRAE, INSERM, Univ Rennes, Saint-Gilles, France
| | - Elise Charton
- Institut NuMeCan, INRAE, INSERM, Univ Rennes, Saint-Gilles, France
- UMR STLO INRAE, Institut Agro, Rennes, France
| | | | | | - Sophie Le Gall
- INRAE, UR BIA, Nantes, France
- INRAE, BIBS facility, Nantes, France
| | | | - Sophie Blat
- Institut NuMeCan, INRAE, INSERM, Univ Rennes, Saint-Gilles, France
| |
Collapse
|
|
17
|
Atyeo C, Alter G. The multifaceted roles of breast milk antibodies. Cell 2021; 184:1486-1499. [PMID: 33740451 DOI: 10.1016/j.cell.2021.02.031] [Citation(s) in RCA: 125] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/07/2021] [Accepted: 02/12/2021] [Indexed: 12/20/2022]
Abstract
Neonates are born with an immature immune system and rely on the transfer of immunity from their mothers. Maternal antibodies are transferred via the placenta and breast milk. Although the role of placentally transferred immunoglobulin G (IgG) is established, less is known about the selection of antibodies transferred via breast milk and the mechanisms by which they provide protection against neonatal disease. Evidence suggests that breast milk antibodies play multifaceted roles, preventing infection and supporting the selection of commensals and tolerizing immunity during infancy. Here, we discuss emerging data related to the importance of breast milk antibodies in neonatal immunity and development.
Collapse
Affiliation(s)
- Caroline Atyeo
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA, USA
| | - Galit Alter
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
| |
Collapse
|
|
18
|
Wei H, Wang JY. Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis. Int J Mol Sci 2021; 22:ijms22052284. [PMID: 33668983 PMCID: PMC7956327 DOI: 10.3390/ijms22052284] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 02/20/2021] [Accepted: 02/22/2021] [Indexed: 12/13/2022] Open
Abstract
Transcytosis of polymeric IgA and IgM from the basolateral surface to the apical side of the epithelium and subsequent secretion into mucosal fluids are mediated by the polymeric immunoglobulin receptor (pIgR). Secreted IgA and IgM have vital roles in mucosal immunity in response to pathogenic infections. Binding and recognition of polymeric IgA and IgM by pIgR require the joining chain (J chain), a small protein essential in the formation and stabilization of polymeric Ig structures. Recent studies have identified marginal zone B and B1 cell-specific protein (MZB1) as a novel regulator of polymeric IgA and IgM formation. MZB1 might facilitate IgA and IgM transcytosis by promoting the binding of J chain to Ig. In this review, we discuss the roles of pIgR in transcytosis of IgA and IgM, the roles of J chain in the formation of polymeric IgA and IgM and recognition by pIgR, and focus particularly on recent progress in understanding the roles of MZB1, a molecular chaperone protein.
Collapse
Affiliation(s)
- Hao Wei
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
| | - Ji-Yang Wang
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
- Department of Clinical Immunology, Children’s Hospital of Fudan University, Shanghai 201102, China
- Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China
- Correspondence: ; Tel.: +86-(21)-54237957
| |
Collapse
|
|
19
|
Kendall E, Millard A, Beaumont J. The "weanling's dilemma" revisited: Evolving bodies of evidence and the problem of infant paleodietary interpretation. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 2021; 175 Suppl 72:57-78. [PMID: 33460467 DOI: 10.1002/ajpa.24207] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 10/23/2020] [Accepted: 12/06/2020] [Indexed: 01/02/2023]
Abstract
Breastfeeding is known to be a powerful mediator of maternal and childhood health, with impacts throughout the life course. Paleodietary studies of the past 30 years have accordingly taken an enduring interest in the health and diet of young children as a potential indicator of population fertility, subsistence, and mortality patterns. While progress has been made in recent decades toward acknowledging the agency of children, many paleodietary reconstructions have failed to incorporate developments in cognate disciplines revealing synergistic dynamics between maternal and offspring biology. Paleodietary interpretation has relied heavily on the "weanling's dilemma," in which infants are thought to face a bleak choice between loss of immunity or malnutrition. Using a review of immunological and epidemiological evidence for the dynamic and supportive role that breastfeeding plays throughout the complementary feeding period, this article offers context and nuance for understanding past feeding transitions. We suggest that future interpretative frameworks for infant paleodietary and bioarchaeological research should include a broad knowledge base that keeps pace with relevant developments outside of those disciplines.
Collapse
Affiliation(s)
- Ellen Kendall
- Department of Archaeology, Durham University, Durham, UK
| | - Andrew Millard
- Department of Archaeology, Durham University, Durham, UK
| | - Julia Beaumont
- School of Archaeological and Forensic Sciences, University of Bradford, Bradford, UK
| |
Collapse
|
|
20
|
McGuire MK, Seppo A, Goga A, Buonsenso D, Collado MC, Donovan SM, Müller JA, Ofman G, Monroy-Valle M, O'Connor DL, Pace RM, Van de Perre P. Best Practices for Human Milk Collection for COVID-19 Research. Breastfeed Med 2021; 16:29-38. [PMID: 33393841 PMCID: PMC7826442 DOI: 10.1089/bfm.2020.0296] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
In addition to providing life-giving nutrients and other substances to the breastfed infant, human milk can also represent a vehicle of pathogen transfer. As such, when an infectious disease outbreak, epidemic, or pandemic occurs-particularly when it is associated with a novel pathogen-the question will naturally arise as to whether the pathogen can be transmitted through breastfeeding. Until high-quality data are generated to answer this question, abandonment of breastfeeding due to uncertainty can result. The COVID-19 pandemic, which was in full swing at the time this document was written, is an excellent example of this scenario. During these times of uncertainty, it is critical for investigators conducting research to assess the possible transmission of pathogens through milk, whether by transfer through the mammary gland or contamination from respiratory droplets, skin, breast pumps, and milk containers, and/or close contact between mother and infant. To promote the most rigorous science, it is critical to outline optimal methods for milk collection, handling, storage, and analysis in these situations, and investigators should openly share their methods in published materials. Otherwise, the risks of inconsistent test results from preanalytical and analytical variation, false positives, and false negatives are unacceptably high and the ability to provide public health guidance poor. In this study, we provide "best practices" for collecting human milk samples for COVID-19 research with the intention that this will also be a useful guide for future pandemics.
Collapse
Affiliation(s)
- Michelle K McGuire
- Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, Idaho, USA
| | - Antti Seppo
- Division of Allergy and Immunology, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
| | - Ameena Goga
- Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa.,HIV Prevention Research Unit, South African Medical Research Council, Cape Town, South Africa.,Department of Pediatrics and Child Health, University of Pretoria, Pretoria, South Africa
| | - Danilo Buonsenso
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy.,Global Health Research Institute, Università Cattolica del Sacro Cuore, Rome, Italia
| | - María Carmen Collado
- Department of Biotechnology, Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), Valencia, Spain
| | - Sharon M Donovan
- Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois, USA
| | - Janis A Müller
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
| | - Gaston Ofman
- College of Medicine, Section of Neonatal-Perinatal Medicine, Oklahoma City, Oklahoma, USA
| | - Michele Monroy-Valle
- Unidad de Investigación en Seguridad Alimentaria y Nutricional, Facultad de Ciencias Químicas y Farmacia Universidad de San Carlos de Guatemala, Guatemala City, Guatemala.,School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Deborah L O'Connor
- Department of Nutritional Sciences, University of Toronto and Translational Medicine Program, The Hospital for Sick Children, Toronto, Canada
| | - Ryan M Pace
- Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, Idaho, USA
| | - Philippe Van de Perre
- Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Franc¸ais du Sang, CHU Montpellier, Montpellier, France
| |
Collapse
|
|
21
|
Ramírez R, Garrido M, Rocha-Pimienta J, García-Parra J, Delgado-Adámez J. Immunological components and antioxidant activity in human milk processed by different high pressure-thermal treatments at low initial temperature and flash holding times. Food Chem 2020; 343:128546. [PMID: 33214041 DOI: 10.1016/j.foodchem.2020.128546] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 10/21/2020] [Accepted: 10/31/2020] [Indexed: 01/02/2023]
Abstract
The effect of high pressure thermal (HPT) processing on the immunoglobulin (IgM, IgA and IgG), and cytokine content (IL-6, IL-8, IL-10, and TNF-α), and antioxidant activity of human milk was analyzed after the application of different treatments between 200, and 800 MPa at low initial temperatures (between -15, and 50 °C) and for 1 s (flash treatments). Low pressures intensities did not induce changes in Igs while at 800 MPa, all combinations reduced the control levels. IL-6 and IL-10 were not affected by any of the treatments applied while IL-8 and TNF-α were reduced at treatments which combined temperatures at 50 °C. In general antioxidant activity was not affected at the processing conditions chosen. The flash HPT treatment applied at 600 MPa and at 0 °C could be the best choice to preserve immunological parameters and the antioxidant activity of human milk.
Collapse
Affiliation(s)
- Rosario Ramírez
- Technological Agri-food Institute (INTAEX), Centro de Investigaciones Científicas y Tecnológicas de Extremadura (CICYTEX), Badajoz, Spain
| | - María Garrido
- Department of Physiology (Neuroimmunophysiology and Chrononutrition Research Group), Faculty of Science, University of Extremadura, Badajoz, Spain
| | - Javier Rocha-Pimienta
- Technological Agri-food Institute (INTAEX), Centro de Investigaciones Científicas y Tecnológicas de Extremadura (CICYTEX), Badajoz, Spain
| | - Jesús García-Parra
- Technological Agri-food Institute (INTAEX), Centro de Investigaciones Científicas y Tecnológicas de Extremadura (CICYTEX), Badajoz, Spain
| | - Jonathan Delgado-Adámez
- Technological Agri-food Institute (INTAEX), Centro de Investigaciones Científicas y Tecnológicas de Extremadura (CICYTEX), Badajoz, Spain.
| |
Collapse
|
|
22
|
In vitro comparison of biofilm formation and acidogenicity between human breast milk and other milk formulas. PEDIATRIC DENTAL JOURNAL 2020. [DOI: 10.1016/j.pdj.2020.06.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
|
|
23
|
Navarro-Tapia E, Sebastiani G, Sailer S, Toledano LA, Serra-Delgado M, García-Algar Ó, Andreu-Fernández V. Probiotic Supplementation During the Perinatal and Infant Period: Effects on Gut Dysbiosis and Disease. Nutrients 2020; 12:E2243. [PMID: 32727119 PMCID: PMC7468726 DOI: 10.3390/nu12082243] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 07/15/2020] [Accepted: 07/22/2020] [Indexed: 02/07/2023] Open
Abstract
The perinatal period is crucial to the establishment of lifelong gut microbiota. The abundance and composition of microbiota can be altered by several factors such as preterm delivery, formula feeding, infections, antibiotic treatment, and lifestyle during pregnancy. Gut dysbiosis affects the development of innate and adaptive immune responses and resistance to pathogens, promoting atopic diseases, food sensitization, and infections such as necrotizing enterocolitis (NEC). Recent studies have indicated that the gut microbiota imbalance can be restored after a single or multi-strain probiotic supplementation, especially mixtures of Lactobacillus and Bifidobacterium strains. Following the systematic search methodology, the current review addresses the importance of probiotics as a preventive or therapeutic tool for dysbiosis produced during the perinatal and infant period. We also discuss the safety of the use of probiotics in pregnant women, preterm neonates, or infants for the treatment of atopic diseases and infections.
Collapse
Affiliation(s)
- Elisabet Navarro-Tapia
- Grup de Recerca Infancia i Entorn (GRIE), Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Valencian International University (VIU), 46002 Valencia, Spain
| | - Giorgia Sebastiani
- Department of Neonatology, Hospital Clínic-Maternitat, ICGON, BCNatal, 08028 Barcelona, Spain
| | - Sebastian Sailer
- Department of Neonatology, Hospital Clínic-Maternitat, ICGON, BCNatal, 08028 Barcelona, Spain
| | - Laura Almeida Toledano
- Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain
- BCNatal, Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), University of Barcelona, 08950 Barcelona, Spain
| | - Mariona Serra-Delgado
- Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain
- BCNatal, Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), University of Barcelona, 08950 Barcelona, Spain
| | - Óscar García-Algar
- Grup de Recerca Infancia i Entorn (GRIE), Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Department of Neonatology, Hospital Clínic-Maternitat, ICGON, BCNatal, 08028 Barcelona, Spain
| | - Vicente Andreu-Fernández
- Grup de Recerca Infancia i Entorn (GRIE), Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Valencian International University (VIU), 46002 Valencia, Spain
- Department of Neonatology, Hospital Clínic-Maternitat, ICGON, BCNatal, 08028 Barcelona, Spain
| |
Collapse
|
|
24
|
Weström B, Arévalo Sureda E, Pierzynowska K, Pierzynowski SG, Pérez-Cano FJ. The Immature Gut Barrier and Its Importance in Establishing Immunity in Newborn Mammals. Front Immunol 2020; 11:1153. [PMID: 32582216 PMCID: PMC7296122 DOI: 10.3389/fimmu.2020.01153] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 05/11/2020] [Indexed: 12/16/2022] Open
Abstract
The gut is an efficient barrier which protects against the passage of pathogenic microorganisms and potential harmful macromolecules into the body, in addition to its primary function of nutrient digestion and absorption. Contrary to the restricted macromolecular passage in adulthood, enhanced transfer takes place across the intestines during early life, due to the high endocytic capacity of the immature intestinal epithelial cells during the fetal and/or neonatal periods. The timing and extent of this enhanced endocytic capacity is dependent on animal species, with a prominent non-selective intestinal macromolecular transfer in newborn ungulates, e.g., pigs, during the first few days of life, and a selective transfer of mainly immunoglobulin G (IgG), mediated by the FcRn receptor, in suckling rodents, e.g., rats and mice. In primates, maternal IgG is transferred during fetal life via the placenta, and intestinal macromolecular transfer is largely restricted in human neonates. The period of intestinal macromolecular transmission provides passive immune protection through the transfer of IgG antibodies from an immune competent mother; and may even have extra-immune beneficial effects on organ maturation in the offspring. Moreover, intestinal transfer during the fetal/neonatal periods results in increased exposure to microbial and food antigens which are then presented to the underlying immune system, which is both naïve and immature. This likely stimulates the maturation of the immune system and shifts the response toward tolerance induction instead of activation or inflammation, as usually seen in adulthood. Ingestion of mother's milk and the dietary transition to complex food at weaning, as well as the transient changes in the gut microbiota during the neonatal period, are also involved in the resulting immune response. Any disturbances in timing and/or balance of these parallel processes, i.e., intestinal epithelial maturation, luminal microbial colonization and mucosal immune maturation due to, e.g., preterm birth, infection, antibiotic use or nutrient changes during the neonatal period, might affect the establishment of the immune system in the infant. This review will focus on how differing developmental processes in the intestinal epithelium affect the macromolecular passage in different species and the possible impact of such passage on the establishment of immunity during the critical perinatal period in young mammals.
Collapse
Affiliation(s)
- Björn Weström
- Department of Biology, Lund University, Lund, Sweden
| | - Ester Arévalo Sureda
- Precision Livestock and Nutrition Unit, TERRA Teaching and Research Centre, Gembloux Agro-Biotech, University of Liège, Gembloux, Belgium
| | - Kateryna Pierzynowska
- Department of Biology, Lund University, Lund, Sweden
- Department of Animal Physiology, Kielanowski Institute of Animal Physiology and Nutrition, Jablonna, Poland
| | - Stefan G. Pierzynowski
- Department of Biology, Lund University, Lund, Sweden
- Department of Medical Biology, Institute of Rural Health, Lublin, Poland
| | - Francisco-José Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain
- Research Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Santa Coloma de Gramenet, Spain
| |
Collapse
|
|
25
|
Cheng L, Akkerman R, Kong C, Walvoort MTC, de Vos P. More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects. Crit Rev Food Sci Nutr 2020; 61:1184-1200. [PMID: 32329623 DOI: 10.1080/10408398.2020.1754756] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Human milk is the gold standard for newborn infants. Breast milk not only provides nutrients, it also contains bioactive components that guide the development of the infant's intestinal immune system, which can have a lifelong effect. The bioactive molecules in breast milk regulate microbiota development, immune maturation and gut barrier function. Human milk oligosaccharides (hMOs) are the most abundant bioactive molecules in human milk and have multiple beneficial functions such as support of growth of beneficial bacteria, anti-pathogenic effects, immune modulating effects, and stimulation of intestine barrier functions. Here we critically review the current insight into the benefits of bioactive molecules in mother milk that contribute to neonatal development and focus on current knowledge of hMO-functions on microbiota and the gastrointestinal immune barrier. hMOs produced via genetically engineered microorganisms are now applied in infant formulas to mimic the nutritional composition of breast milk as closely as possible, and their prospects and scientific challenges are discussed in depth.
Collapse
Affiliation(s)
- Lianghui Cheng
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Renate Akkerman
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Chunli Kong
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Marthe T C Walvoort
- Stratingh Institute for Chemistry, Faculty of Science and Engineering, University of Groningen, Groningen, Netherlands
| | - Paul de Vos
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| |
Collapse
|
|
26
|
The Ecology of Breastfeeding and Mother-Infant Immune Functions. THE MOTHER-INFANT NEXUS IN ANTHROPOLOGY 2020. [DOI: 10.1007/978-3-030-27393-4_5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
|
|
27
|
Lundgren SN, Madan JC, Karagas MR, Morrison HG, Hoen AG, Christensen BC. Microbial Communities in Human Milk Relate to Measures of Maternal Weight. Front Microbiol 2019; 10:2886. [PMID: 31921063 PMCID: PMC6933483 DOI: 10.3389/fmicb.2019.02886] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 11/29/2019] [Indexed: 12/22/2022] Open
Abstract
The process of breastfeeding exposes infants to bioactive substances including a diversity of bacteria from breast milk as well as maternal skin. Knowledge of the character of and variation in these microbial communities, as well as the factors that influence them, is limited. We aimed to identify profiles of breastfeeding-associated microbial communities and their association with maternal and infant factors. Bilateral milk samples were collected from women in the New Hampshire Birth Cohort Study at approximately 6 weeks postpartum without sterilization of the skin in order to capture the infant-relevant exposure. We sequenced the V4-V5 hypervariable region of the bacterial 16S rRNA gene in 155 human milk samples. We used unsupervised clustering (partitioning around medoids) to identify microbial profiles in milk samples, and multinomial logistic regression to test their relation with maternal and infant variables. Associations between alpha diversity and maternal and infant factors were tested with linear models. Four breastfeeding microbiome types (BMTs) were identified, which differed in alpha diversity and in Streptococcus, Staphylococcus, Acinetobacter, and Pseudomonas abundances. Higher maternal pre-pregnancy BMI was associated with increased odds of belonging to BMT1 [OR (95% CI) = 1.13 (1.02, 1.24)] or BMT3 [OR (95% CI) = 1.12 (1.01, 1.25)] compared to BMT2. Independently, increased gestational weight gain was related to reduced odds of membership in BMT1 [OR (95% CI) = 0.66 (0.44, 1.00) per 10 pounds]. Alpha diversity was positively associated with gestational weight gain and negatively associated with postpartum sample collection week. There were no statistically significant associations of breastfeeding microbiota with delivery mode. Our results indicate that the breastfeeding microbiome partitions into four profiles and that its composition and diversity is associated with measures of maternal weight.
Collapse
Affiliation(s)
- Sara N. Lundgren
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
| | - Juliette C. Madan
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Division of Neonatology, Department of Pediatrics, Children’s Hospital at Dartmouth, Lebanon, NH, United States
| | - Margaret R. Karagas
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Hilary G. Morrison
- Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, MA, United States
| | - Anne G. Hoen
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Brock C. Christensen
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| |
Collapse
|
|
28
|
Zika Virus Alters the Viscosity and Cytokines Profile in Human Colostrum. J Immunol Res 2019; 2019:9020519. [PMID: 31828175 PMCID: PMC6885239 DOI: 10.1155/2019/9020519] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 10/14/2019] [Indexed: 12/13/2022] Open
Abstract
The resurgence of cases of Zika virus (ZIKV) infection, accompanied by epidemic of microcephaly in Brazil, has aroused worldwide interest in understanding the biological mechanisms of the virus that allow patient management and the viral dissemination control. Colostrum and human milk are possible sources of virus spread. Therefore, the objective of this study was to analyze the repercussions of ZIKV infection on rheological parameters and inflammatory cytokines of colostrum. The prospective cohort study included 40 puerperal donors of colostrum, divided into 2 groups: control (without ZIKV infection, n = 20) and a group infected with ZIKV during the gestational period (n = 20). Analyses were performed for the detection of ZIKV by polymerase chain reaction (PCR). In addition to obtaining the rheological parameters and quantification of IL-10 and IL-6 cytokines by flow cytometry, ZIKV and other flaviviruses were not detected in colostrum. However, maternal infection reflected increased viscosity, decreased levels of IL-10, and elevated levels of IL-6. The higher viscosity may represent a mechanical barrier that hinders the spread of the virus. The lower levels of anti-inflammatory mediators and higher inflammatory cytokines may possibly alter the viscosity, and it seems the higher viscosity represents a possible mechanism of adaptation of breastfeeding against a response to ZIKV.
Collapse
|
|
29
|
Demers-Mathieu V, Huston RK, Markell AM, McCulley EA, Martin RL, Spooner M, Dallas DC. Differences in Maternal Immunoglobulins within Mother's Own Breast Milk and Donor Breast Milk and across Digestion in Preterm Infants. Nutrients 2019; 11:nu11040920. [PMID: 31022910 PMCID: PMC6521323 DOI: 10.3390/nu11040920] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 04/08/2019] [Accepted: 04/22/2019] [Indexed: 02/06/2023] Open
Abstract
Maternal antibody transfer to the newborn provides essential support for the infant’s naïve immune system. Preterm infants normally receive maternal antibodies through mother’s own breast milk (MBM) or, when mothers are unable to provide all the milk required, donor breast milk (DBM). DBM is pasteurized and exposed to several freeze–thaw cycles, which could reduce intact antibody concentration and the antibody’s resistance to digestion within the infant. Whether concentrations of antibodies in MBM and DBM differ and whether their survival across digestion in preterm infants differs remains unknown. Feed (MBM or DBM), gastric contents (MBM or DBM at 1-h post-ingestion) and stool samples (collected after a mix of MBM and DBM feeding) were collected from 20 preterm (26–36 weeks gestational age) mother–infant pairs at 8–9 and 21–22 days of postnatal age. Samples were analyzed via ELISA for the concentration of secretory IgA (SIgA), total IgA (SIgA/IgA), total IgM (SIgM/IgM) and IgG. Total IgA, SIgA, total IgM and IgG concentrations were 55.0%, 71.6%, 98.4% and 41.1% higher in MBM than in DBM, and were 49.8%, 32.7%, 73.9% and 39.7% higher in gastric contents when infants were fed with MBM than when infants were fed DBM, respectively. All maternal antibody isotypes present in breast milk were detected in the infant stools, of which IgA (not sIgA) was the most abundant.
Collapse
Affiliation(s)
- Veronique Demers-Mathieu
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA.
| | - Robert K Huston
- Department of Pediatrics, Randall Children's Hospital at Legacy Emanuel, Portland, OR 97227, USA.
| | - Andi M Markell
- Department of Pediatrics, Randall Children's Hospital at Legacy Emanuel, Portland, OR 97227, USA.
| | - Elizabeth A McCulley
- Department of Pediatrics, Randall Children's Hospital at Legacy Emanuel, Portland, OR 97227, USA.
| | - Rachel L Martin
- Department of Pediatrics, Randall Children's Hospital at Legacy Emanuel, Portland, OR 97227, USA.
| | - Melinda Spooner
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA.
| | - David C Dallas
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA.
| |
Collapse
|
|
30
|
Kim LY, McGrath-Morrow SA, Collaco JM. Impact of breast milk on respiratory outcomes in infants with bronchopulmonary dysplasia. Pediatr Pulmonol 2019; 54:313-318. [PMID: 30609293 PMCID: PMC6518393 DOI: 10.1002/ppul.24228] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Accepted: 11/15/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND The objective of our study was to examine whether outpatient respiratory morbidities in infants with bronchopulmonary dysplasia (BPD) are influenced by the human milk consumption. METHODS Caregivers of subjects recruited from a BPD clinic completed questionnaires regarding breast milk intake and respiratory outcomes. RESULTS One-hundred eighty-eight caregivers completed the questionnaire. Of these, 173 (92.0%) reported that the child received some breast milk. Infants who received breast milk for fewer months were more likely to be non-white, and have a lower household income, public insurance, and secondhand smoke exposure. A longer receipt of breast milk was associated with reduced likelihoods of emergency department visits, systemic steroid courses, and cough or chest congestion, and a trend towards a lower risk of re-hospitalizations. CONCLUSIONS Longer duration of breast milk intake was associated with markers of higher socio-economic status, and reduced likelihood of acute and chronic respiratory morbidities among preterm infants with bronchopulmonary dysplasia.
Collapse
Affiliation(s)
- Lydia Y Kim
- Eudowood Division of Pediatric Respiratory Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sharon A McGrath-Morrow
- Eudowood Division of Pediatric Respiratory Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Joseph M Collaco
- Eudowood Division of Pediatric Respiratory Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
| |
Collapse
|
|
31
|
Ulfman LH, Leusen JHW, Savelkoul HFJ, Warner JO, van Neerven RJJ. Effects of Bovine Immunoglobulins on Immune Function, Allergy, and Infection. Front Nutr 2018; 5:52. [PMID: 29988421 PMCID: PMC6024018 DOI: 10.3389/fnut.2018.00052] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 05/30/2018] [Indexed: 12/12/2022] Open
Abstract
This review aims to provide an in depth overview of the current knowledge of the effects of bovine immunoglobulins on the human immune system. The stability and functional effects of orally ingested bovine immunoglobulins in milk products are described and potential mechanisms of action are discussed. Orally ingested bovine IgG (bovine IgG) can be recovered from feces, ranging from very low levels up to 50% of the ingested IgG that has passed through the gastrointestinal tract. In infants the recovered levels are higher than in adults most likely due to differences in stomach and intestinal conditions such as pH. This indicates that bovine IgG can be functionally active throughout the gastrointestinal tract. Indeed, a large number of studies in infants and adults have shown that bovine IgG (or colostrum as a rich source thereof) can prevent gastrointestinal tract infections, upper respiratory tract infections, and LPS-induced inflammation. These studies vary considerably in target group, design, source of bovine IgG, dosage, and endpoints measured making it hard to draw general conclusions on effectiveness of bovine immunoglobulin rich preparations. Typical sources of bovine IgG used in human studies are serum-derived IgG, colostrum, colostrum-derived IgG, or milk-derived immunoglobulins. In addition, many studies have used IgG from vaccinated cows, but studies using IgG from nonimmunized animals have also been reported to be effective. Mechanistically, bovine IgG binds to many human pathogens and allergens, can neutralize experimental infection of human cells, and limits gastrointestinal inflammation. Furthermore, bovine IgG binds to human Fc receptors which, enhances phagocytosis, killing of bacteria and antigen presentation and bovine IgG supports gastrointestinal barrier function in in vitro models. These mechanisms are becoming more and more established and explain why bovine IgG can have immunological effects in vivo. The inclusion of oral bovine immunoglobulins in specialized dairy products and infant nutrition may therefore be a promising approach to support immune function in vulnerable groups such as infants, children, elderly and immunocompromised patients.
Collapse
Affiliation(s)
| | - Jeanette H W Leusen
- Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Huub F J Savelkoul
- Wageningen University & Research, Cell Biology and Immunology, Wageningen, Netherlands.,Allergy Consortium Wageningen, Wageningen, Netherlands
| | - John O Warner
- National Institute of Health Research, Collaboration for Leadership in Applied Health Research and Care for NW London, Imperial College, London, United Kingdom
| | - R J Joost van Neerven
- FrieslandCampina, Amersfoort, Netherlands.,Wageningen University & Research, Cell Biology and Immunology, Wageningen, Netherlands
| |
Collapse
|
|
32
|
Demers-Mathieu V, Underwood MA, Beverly RL, Nielsen SD, Dallas DC. Comparison of Human Milk Immunoglobulin Survival during Gastric Digestion between Preterm and Term Infants. Nutrients 2018; 10:E631. [PMID: 29772785 PMCID: PMC5986510 DOI: 10.3390/nu10050631] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 05/11/2018] [Accepted: 05/14/2018] [Indexed: 02/02/2023] Open
Abstract
Human milk provides immunoglobulins (Igs) that supplement the passive immune system of neonates; however, the extent of survival of these Igs during gastric digestion and whether this differs between preterm and term infants remains unknown. Human milk, and infant gastric samples at 2 h post-ingestion were collected from 15 preterm (23⁻32 week gestational age (GA)) mother-infant pairs and from 8 term (38⁻40 week of GA) mother-infant pairs within 7⁻98 days postnatal age. Samples were analyzed via ELISA for concentration of total IgA (secretory IgA (SIgA)/IgA), total secretory component (SC/SIgA/SIgM), total IgM (SIgM/IgM), and IgG as well as peptidomics. Total IgA concentration decreased by 60% from human milk to the preterm infant stomach and decreased by 48% in the term infant stomach. Total IgM and IgG concentrations decreased by 33% and 77%, respectively, from human milk to the term infant stomach but were stable in the preterm infant stomach. Release of peptides from all Ig isotypes in the term infant stomach was higher than in the preterm stomach. Overall, the stability of human milk Igs during gastric digestion is higher in preterm infant than in term infants, which could be beneficial for assisting the preterm infants' immature immune system.
Collapse
Affiliation(s)
- Veronique Demers-Mathieu
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA.
| | - Mark A Underwood
- Department of Pediatrics, University of California, Davis, Sacramento, CA 95817, USA.
| | - Robert L Beverly
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA.
| | - Søren D Nielsen
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA.
| | - David C Dallas
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA.
| |
Collapse
|
|
33
|
Khan SM, Speizer IS, Singh K, Angeles G, Twum-Danso NA, Barker P. Does postnatal care have a role in improving newborn feeding? A study in 15 sub-Saharan African countries. J Glob Health 2018; 7:020506. [PMID: 29423183 PMCID: PMC5785869 DOI: 10.7189/jogh.07.020506] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background Breastfeeding is known as a key intervention to improve newborn health and survival while prelacteal feeds (liquids other than breastmilk within 3 days of birth) represents a departure from optimal feeding practices. Recent programmatic guidelines from the WHO and UNICEF outline the need to improve newborn feeding and points to postnatal care (PNC) as a potential mechanism to do so. This study examines if PNC and type of PNC provider are associated with key newborn feeding practices: breastfeeding within 1 day and prelacteal feeds. Methods We use data from the Demographic and Health Surveys for 15 sub-Saharan African countries to estimate 4 separate pooled, multilevel, logistic regression models to predict the newborn feeding outcomes. Findings PNC is significantly associated with increased breastfeeding within 1day (OR = 1.35, P < 0.001) but is not associated with PLFs (OR = 1.04, P = 0.195). PNC provided by nurses, midwives and untrained health workers is also associated with higher odds of breastfeeding within 1 day of birth (OR = 1.39, P < 0.001, (OR = 1.95, P < 0.001) while PNC provided by untrained health workers is associated with increased odds of PLFs (OR = 1.20, P = 0.017). Conclusions PNC delivered through customary care may be an effective strategy to improve the breastfeeding within 1 day but not to discourage PLFs. Further analysis should be done to examine how these variables operate at the country level to produce finer programmatic insight.
Collapse
Affiliation(s)
- Shane M Khan
- Data and Analytics, Division of Data, Research and Policy, United Nations Children's Fund (UNICEF), New York, New York, USA
| | - Ilene S Speizer
- Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Kavita Singh
- Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Gustavo Angeles
- Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Nana Ay Twum-Danso
- Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Pierre Barker
- Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| |
Collapse
|
|
34
|
Molès JP, Tuaillon E, Kankasa C, Bedin AS, Nagot N, Marchant A, McDermid JM, Van de Perre P. Breastmilk cell trafficking induces microchimerism-mediated immune system maturation in the infant. Pediatr Allergy Immunol 2018; 29:133-143. [PMID: 29197124 DOI: 10.1111/pai.12841] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/28/2017] [Indexed: 12/31/2022]
Abstract
Initiating breastfeeding within the first hour of life confers an important benefit in terms of child mortality and severe morbidity. Intestinal permeability to ingested macromolecules and immunoglobulins is limited to the first days of human life. These exchanges cease in the very early post-partum period but may increase beyond the neonatal period in response to local inflammation or introduction of a weaning food. From animal- and limited human-based observations, compelling evidence points out to breastmilk cells also trafficking from mother to infant mucosal tissues and participating to the maternal microchimerism. The precise nature of breastmilk cells that are involved is presently not known but likely includes progenitor/stem cells-representing up to 6% of breastmilk cells-with possible contribution of mature immune cells. Stem cell microchimerism may induce tolerance to non-inherited maternal antigens (NIMAs), breastfeeding generating regulatory T cells (Treg ) that suppress antimaternal immunity. Therefore, in complement to pregnancy-induced microchimerism, breastfeeding-induced microchimerism may be pivotal in infant immune development, intestinal tissue repair/growth and protection against infectious diseases. As a continuum of the gestational period, the neonatal gut may be considered as a temporary, but important developmental extension of the role played by the placenta during intrauterine life; breastmilk playing the role of maternal blood by delivering maternal soluble factors (macromolecules, Ig, cytokines) and immunologically active milk cells. A better understanding of breastfeeding-induced maternal microchimerism would provide further evidence in support of public health messages that reinforce the importance of early initiation of breastfeeding.
Collapse
Affiliation(s)
- Jean-Pierre Molès
- Pathogenesis and Control of Chronic Infections, INSERM, EFS, Université de Montpellier, Montpellier, France
| | - Edouard Tuaillon
- Pathogenesis and Control of Chronic Infections, INSERM, EFS, Université de Montpellier, Montpellier, France.,Department of Bacteriology-Virology and Department of Medical Information, CHU Montpellier, Montpellier, France
| | - Chipepo Kankasa
- Department of Paediatrics and Child Health, School of Medicine, University Teaching Hospital, University of Zambia, Lusaka, Zambia
| | - Anne-Sophie Bedin
- Pathogenesis and Control of Chronic Infections, INSERM, EFS, Université de Montpellier, Montpellier, France
| | - Nicolas Nagot
- Pathogenesis and Control of Chronic Infections, INSERM, EFS, Université de Montpellier, Montpellier, France.,Department of Bacteriology-Virology and Department of Medical Information, CHU Montpellier, Montpellier, France
| | - Arnaud Marchant
- Institute for Medical Immunology, Université Libre de Bruxelles, Brussels, Belgium
| | - Joann M McDermid
- Division of Infectious Diseases & International Health, Department of Medicine, School of Medicine, University of Virginia, Charlottesville, VA, USA
| | - Philippe Van de Perre
- Pathogenesis and Control of Chronic Infections, INSERM, EFS, Université de Montpellier, Montpellier, France.,Department of Bacteriology-Virology and Department of Medical Information, CHU Montpellier, Montpellier, France
| |
Collapse
|
|
35
|
Waidyatillake NT, Dharmage SC, Allen KJ, Lodge CJ, Simpson JA, Bowatte G, Abramson MJ, Lowe AJ. Association of breast milk fatty acids with allergic disease outcomes-A systematic review. Allergy 2018; 73:295-312. [PMID: 28869762 DOI: 10.1111/all.13300] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2017] [Indexed: 01/21/2023]
Abstract
INTRODUCTION Dietary polyunsaturated fatty acids (PUFAs) have immunoregulatory properties. Breast milk is rich in PUFA, and it has been hypothesized that these PUFAs may be important in the aetiology of allergic diseases. Despite a growing body of evidence, the associations between breast milk PUFA and allergic disease have not previously been systematically reviewed. METHODS The search was performed in PubMed and EMBASE databases using breastfeeding, fatty acid and allergic disease terms. Two authors were involved in selecting papers for review according to the inclusion criteria and extracting information on study characteristics and measures of association. Only studies that reported numeric associations between concentration of breast milk fatty acids and allergic disease outcomes were included. RESULTS A total of 18 papers met the inclusion criteria, reporting results from 15 study populations. The majority were cohort studies (n=11), with data from only two case-control and two cross-sectional studies. Sample size varied between 30 and 352 participants, and follow-up time of the cohorts varied between 3 months and 14 years. Nine studies reported on eczema, seven reported on sensitization, and only five reported on asthma/wheeze. There was heterogeneity among studies in terms of presenting the association between PUFA and allergy; therefore, estimates could not be pooled. Only a few studies observed associations between n-3 and n-6 PUFAs and allergic disease, and the magnitude of this effect varied greatly. CONCLUSIONS There is insufficient evidence to suggest that colostrum or breast milk polyunsaturated fatty acids influence the risk of childhood allergic diseases.
Collapse
Affiliation(s)
- N. T. Waidyatillake
- Allergy and Lung Health Unit; Centre for Epidemiology and Biostatistics; Melbourne School of Population and Global Health; The University of Melbourne; Melbourne VIC Australia
| | - S. C. Dharmage
- Allergy and Lung Health Unit; Centre for Epidemiology and Biostatistics; Melbourne School of Population and Global Health; The University of Melbourne; Melbourne VIC Australia
- Murdoch Childrens Research Institute; Melbourne VIC Australia
| | - K. J. Allen
- Murdoch Childrens Research Institute; Melbourne VIC Australia
| | - C. J. Lodge
- Allergy and Lung Health Unit; Centre for Epidemiology and Biostatistics; Melbourne School of Population and Global Health; The University of Melbourne; Melbourne VIC Australia
- Murdoch Childrens Research Institute; Melbourne VIC Australia
| | - J. A. Simpson
- Biostatistics Unit; Centre for Epidemiology and Biostatistics; Melbourne School of Population and Global Health; The University of Melbourne; Melbourne VIC Australia
| | - G. Bowatte
- Allergy and Lung Health Unit; Centre for Epidemiology and Biostatistics; Melbourne School of Population and Global Health; The University of Melbourne; Melbourne VIC Australia
| | - M. J. Abramson
- School of Public Health & Preventive Medicine; Monash University; Melbourne VIC Australia
| | - A. J. Lowe
- Allergy and Lung Health Unit; Centre for Epidemiology and Biostatistics; Melbourne School of Population and Global Health; The University of Melbourne; Melbourne VIC Australia
- Murdoch Childrens Research Institute; Melbourne VIC Australia
| |
Collapse
|
|
36
|
Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques. mSphere 2018; 3:mSphere00505-17. [PMID: 29359183 PMCID: PMC5760748 DOI: 10.1128/msphere.00505-17] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 12/11/2017] [Indexed: 01/20/2023] Open
Abstract
Without novel strategies to prevent mother-to-child HIV-1 transmission, more than 5% of HIV-1-exposed infants will continue to acquire HIV-1, most through breastfeeding. This study of rhesus macaque dam-and-infant pairs is the first preclinical study to investigate the protective role of transplacentally transferred HIV-1 vaccine-elicited antibodies and HIV-1 vaccine-elicited breast milk antibody responses in infant oral virus acquisition. It revealed highly variable placental transfer of potentially protective antibodies and emphasized the importance of pregnancy immunization timing to reach peak antibody levels prior to delivery. While there was no discernible impact of maternal immunization on late infant oral virus acquisition, we observed a strong correlation between the percentage of activated CD4+ T cells in infant peripheral blood and a reduced number of challenges to infection. This finding highlights an important consideration for future studies evaluating alternative strategies to further reduce the vertical HIV-1 transmission risk. Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the potentially protective immune responses necessary to inhibit HIV-1 infection of infants through breastfeeding. In the present study, we tested the efficacy of a maternal vaccine regimen consisting of a modified vaccinia virus Ankara (MVA) 1086.C gp120 prime-combined intramuscular-intranasal gp120 boost administered during pregnancy and postpartum to confer passive protection on infant rhesus macaques against weekly oral exposure to subtype C simian-human immunodeficiency virus 1157ipd3N4 (SHIV1157ipd3N4) starting 6 weeks after birth. Despite eliciting a robust systemic envelope (Env)-specific IgG response, as well as durable milk IgA responses, the maternal vaccine did not have a discernible impact on infant oral SHIV acquisition. This study revealed considerable variation in vaccine-elicited IgG placental transfer and a swift decline of both Env-specific antibodies (Abs) and functional Ab responses in the infants prior to the first challenge, illustrating the importance of pregnancy immunization timing to elicit optimal systemic Ab levels at birth. Interestingly, the strongest correlation to the number of challenges required to infect the infants was the percentage of activated CD4+ T cells in the infant peripheral blood at the time of the first challenge. These findings suggest that, in addition to maternal immunization, interventions that limit the activation of target cells that contribute to susceptibility to oral HIV-1 acquisition independently of vaccination may be required to reduce infant HIV-1 acquisition via breastfeeding. IMPORTANCE Without novel strategies to prevent mother-to-child HIV-1 transmission, more than 5% of HIV-1-exposed infants will continue to acquire HIV-1, most through breastfeeding. This study of rhesus macaque dam-and-infant pairs is the first preclinical study to investigate the protective role of transplacentally transferred HIV-1 vaccine-elicited antibodies and HIV-1 vaccine-elicited breast milk antibody responses in infant oral virus acquisition. It revealed highly variable placental transfer of potentially protective antibodies and emphasized the importance of pregnancy immunization timing to reach peak antibody levels prior to delivery. While there was no discernible impact of maternal immunization on late infant oral virus acquisition, we observed a strong correlation between the percentage of activated CD4+ T cells in infant peripheral blood and a reduced number of challenges to infection. This finding highlights an important consideration for future studies evaluating alternative strategies to further reduce the vertical HIV-1 transmission risk.
Collapse
|
|
37
|
Demers-Mathieu V, Underwood MA, Beverly RL, Dallas DC. Survival of Immunoglobulins from Human Milk to Preterm Infant Gastric Samples at 1, 2, and 3 h Postprandial. Neonatology 2018; 114:242-250. [PMID: 29940583 PMCID: PMC6217945 DOI: 10.1159/000489387] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 04/17/2018] [Indexed: 10/28/2022]
Abstract
BACKGROUND Human milk immunoglobulins (Ig) are an important support for the naïve infant immune system; yet the extent to which these proteins survive within the infant digestive tract, particularly for preterm infants, is poorly studied. OBJECTIVES Our objective was to evaluate the survival of human milk Igs in the preterm stomach across postprandial time. METHODS Human milk and infant gastric samples were collected from 11 preterm (23-32 weeks gestational age) mother-infant pairs within 7-98 days postnatal age. Preterm gastric samples were collected 1, 2, and 3 h after the beginning of the feeding. Samples were analyzed for concentration of total IgA (secretory IgA [SIgA]/IgA), total secretory component (SC/SIgA/SIgM), total IgM (SIgM/IgM), and IgG via enzyme-linked immunosorbent assay. Ig-chain fragment peptides were determined using peptidomic analysis. One-way analysis of variance with repeated measures followed by Tukey's multiple comparison tests was applied. RESULTS Concentrations of total IgA were lower in the gastric contents at 3 h postprandial compared with human milk and gastric contents at 1 and 2 h. Human milk SC/SIgA/SIgM, IgG, and total IgM concentrations remained stable in the preterm stomach across postprandial time. Peptide counts from the Ig alpha-chain and the Ig gamma-chain increased in gastric contents from 1 to 2 h postprandial. Peptide counts from the human milk Ig-chain, Ig-chain, and SC were stable across postprandial time. These peptides from Ig-chains were not present in human milk but were released in the stomach due to their partial degradation. CONCLUSIONS Human milk total SC (SIgA/SC/SIgM), total IgM, and IgG survived mostly intact through the preterm infant stomach, while total IgA was -partially digested.
Collapse
Affiliation(s)
- Veronique Demers-Mathieu
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon, USA
| | - Mark A Underwood
- Department of Pediatrics, University of California, Sacramento, California, USA
| | - Robert L Beverly
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon, USA
| | - David C Dallas
- Nutrition Program, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon, USA
| |
Collapse
|
|
38
|
|
|
39
|
Dasgupta S, Jain SK. Protective effects of amniotic fluid in the setting of necrotizing enterocolitis. Pediatr Res 2017; 82:584-595. [PMID: 28609432 DOI: 10.1038/pr.2017.144] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Accepted: 05/03/2017] [Indexed: 12/16/2022]
Abstract
Necrotizing enterocolitis (NEC) is the most common life threatening condition affecting preterm infants. NEC occurs in 1-5% of all neonatal intensive care admissions and 5-10% of very low birth weight infants. The protective role of human breast milk (BM) has been well established. It has also been shown that amniotic fluid (AF) and BM have many similarities in terms of presence of growth and other immune-modulatory factors. This finding led to the initial hypothesis that AF may exert similar protective effects against the development of NEC, as does BM. Multiple studies have elucidated the presence of growth factors in AF and the protective effect of AF against NEC. Studies have also described possible mechanisms how AF protects against NEC. At present, research in this particular area is extremely active and robust. This review summarizes the various studies looking at the protective effects of AF against the development of NEC. It also provides an insight into future directions, the vast potential of AF as a readily available biologic medium, and the ethical barriers that must be overcome before using AF.
Collapse
Affiliation(s)
- Soham Dasgupta
- Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas
| | - Sunil Kumar Jain
- Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas
| |
Collapse
|
|
40
|
Cacho NT, Lawrence RM. Innate Immunity and Breast Milk. Front Immunol 2017; 8:584. [PMID: 28611768 PMCID: PMC5447027 DOI: 10.3389/fimmu.2017.00584] [Citation(s) in RCA: 239] [Impact Index Per Article: 29.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 05/01/2017] [Indexed: 12/16/2022] Open
Abstract
Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant's optimal growth and development. The growing infant's immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant's innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk's effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant's intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant's gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing infant.
Collapse
Affiliation(s)
- Nicole Theresa Cacho
- Division of Neonatology, Department of Pediatrics, University of Florida, Gainesville, FL, United States
| | - Robert M Lawrence
- Division of Pediatric Infectious Disease, Department of Pediatrics, University of Florida, Gainesville, FL, United States
| |
Collapse
|
|
41
|
Lactoferrin concentration in breast milk of mothers of low-birth-weight newborns. J Perinatol 2017; 37:507-512. [PMID: 28125095 PMCID: PMC5554708 DOI: 10.1038/jp.2016.265] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 11/11/2016] [Accepted: 12/16/2016] [Indexed: 01/28/2023]
Abstract
OBJECTIVES Lactoferrin (LF) is a breast milk glycoprotein with protective effects against neonatal infections, mainly in premature and low-birth-weight (LBW) neonates. The aims of this study were to determine LF concentration in breast milk of mothers of LBW infants during the first 2 months postpartum, and to identify the factors associated with LF concentration. STUDY DESIGN Prospective study conducted as a part of an ongoing clinical trial in three Neonatal Units in Peru. We included 346 mothers of neonates with a birth weight <2000 g. We measured LF concentration in four stages of lactation using a commercial enzyme-linked immunosorbent assay kit. Multivariate analysis was performed to assess the association between maternal and neonatal factors, and LF concentration. RESULTS We collected 695 milk samples. LF mean concentration±standard deviation was 14.92±7.96 mg ml-1 in colostrum (n=277), 10.73±5.67 in transitional milk (n=55), 10.34±6.27 at 1 month (n=259) and 8.52±6.47 at 2 months (n=104). There was a significant difference in LF concentration between different stages of lactation (P<0.001). Mothers with higher LF concentration in colostrum had higher values in the following 2 months. High maternal income and multiple gestation were significantly associated with higher LF levels; in contrast, maternal peripartum infections and male neonatal gender were associated with lower LF levels. CONCLUSIONS LF concentration in breast milk of mothers of LBW infants was high and remained elevated even at 1 and 2 months postpartum. LF concentration in colostrum was higher in mothers with higher income and multiple pregnancies, and lower in mothers with peripartum infections.
Collapse
|
|
42
|
Garcia M, Power ML, Moyes KM. Immunoglobulin A and nutrients in milk from great apes throughout lactation. Am J Primatol 2016; 79:1-11. [PMID: 28118501 DOI: 10.1002/ajp.22614] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Differences in macronutrients between human and ape milks appear relatively small, but variation in other components such as immunoglobulins (Ig) may be greater. This study characterized the macronutrient and secretory (sIgA) profiles in milk from gorillas and orangutans throughout lactation. Fifty-three milk samples from four gorillas and three orangutans were collected throughout 48 and 22 months postpartum (MPP), respectively. Samples were grouped in five stages of lactation (0 to 6 months, more than 6 months to 12 months, more than 12 months to 18 months, more than 18 months to 36 months, and more than 36 months to 48 months). Data were analyzed as a complete randomized design. Concentration of sIgA did not change due to species or its interaction with MPP. Crude protein, regardless of MPP, was greater for gorillas compared with orangutans (1.27 vs. 0.85%). Fat, sugar, and gross energy were affected by the interaction of species × MPP. For gorilla milk, concentrations of sIgA were 43 mg/L at 6 MPP increasing to 79 mg/L at 48 MPP. Protein was highest at 48 MPP. Sugar was lowest at 48 MPP. Values for fat and gross energy were the highest 36 MPP. For orangutan milk, concentrations of sIgA were highest at 6 MPP. Sugar decreased with MPP. Protein, dry matter, or fat were unaffected by MPP. Gross energy content was steady during the first 18 MPP but it tended to decrease by 36 MPP. The results indicate that macronutrients are similar between human, published data, and great ape milk, though gorilla milk has higher protein and human milk higher fat (published data). Concentrations of sIgA in ape milk were about 10-fold lower than human values from the literature. Differences between human and ape milk may lie more in bioactive/immune molecules than nutrients. RESEARCH HIGHLIGHTS Milk macronutrients from great apes differed throughout lactation. Milk macronutrients but not IgA from non-human great apes and humans were quite similar. Milk protein was greater in Gorilla compared with Orangutan.
Collapse
Affiliation(s)
- Miriam Garcia
- Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland
| | - Michael L Power
- Nutrition Laboratory, Smithsonian National Zoological Park, Washington, District of Columbia
| | - Kasey M Moyes
- Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland
| |
Collapse
|
|
43
|
Temporal Changes of Protein Composition in Breast Milk of Chinese Urban Mothers and Impact of Caesarean Section Delivery. Nutrients 2016; 8:nu8080504. [PMID: 27548208 PMCID: PMC4997417 DOI: 10.3390/nu8080504] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 07/29/2016] [Accepted: 08/01/2016] [Indexed: 11/24/2022] Open
Abstract
Human breast milk (BM) protein composition may be impacted by lactation stage or factors related to geographical location. The present study aimed at assessing the temporal changes of BM major proteins over lactation stages and the impact of mode of delivery on immune factors, in a large cohort of urban mothers in China. 450 BM samples, collected in three Chinese cities, covering 8 months of lactation were analyzed for α-lactalbumin, lactoferrin, serum albumin, total caseins, immunoglobulins (IgA, IgM and IgG) and transforming growth factor (TGF) β1 and β2 content by microfluidic chip- or ELISA-based quantitative methods. Concentrations and changes over lactation were aligned with previous reports. α-lactalbumin, lactoferrin, IgA, IgM and TGF-β1 contents followed similar variations characterized by highest concentrations in early lactation that rapidly decreased before remaining stable up to end of lactation. TGF-β2 content displayed same early dynamics before increasing again. Total caseins followed a different pattern, showing initial increase before decreasing back to starting values. Serum albumin and IgG levels appeared stable throughout lactation. In conclusion, BM content in major proteins of urban mothers in China was comparable with previous studies carried out in other parts of the world and C-section delivery had only very limited impact on BM immune factors.
Collapse
|
|
44
|
Villavicencio A, Rueda MS, Turin CG, Ochoa TJ. Factors affecting lactoferrin concentration in human milk: how much do we know? Biochem Cell Biol 2016; 95:12-21. [PMID: 28075610 DOI: 10.1139/bcb-2016-0060] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Lactoferrin (LF) is a breast milk glycoprotein with antimicrobial and anti-inflammatory effects. Its beneficial properties in infants, especially in those born preterm, are currently being studied in clinical trials. However, the maternal and nursing infant factors that may affect LF concentration in breast milk are still not clear. We conducted a systematic review to investigate the factors that may affect the concentration of LF in breast milk. We used a 2-step approach to identify the eligible studies according to inclusion/exclusion criteria, and to determine which studies would be considered. We included 70 qualified articles from 29 countries with publication dates ranging from 1976 to 2015. We described the correlation between LF concentration in breast milk and lactation stage; 10 maternal factors, such as race, parity, among others; and 2 infant factors: infections and prematurity. Colostrum has the highest LF levels, but they decrease with days postpartum. No other factor has been consistently associated with LF concentration. A major limitation of the majority of the published studies is the small sample size and the different methods used to measure LF concentration. Therefore, there is a need for large, multicenter studies with standardized study design, sample collection, and LF measurement methods to identify clinically significant factors associated with LF expression in breast milk, which will help promote exclusive breastfeeding in preterm infants.
Collapse
Affiliation(s)
- Aasith Villavicencio
- a Instituto de Medicina Tropical "Alexander von Humboldt", Universidad Peruana Cayetano Heredia, Lima 31, Peru
| | - Maria S Rueda
- a Instituto de Medicina Tropical "Alexander von Humboldt", Universidad Peruana Cayetano Heredia, Lima 31, Peru
| | - Christie G Turin
- a Instituto de Medicina Tropical "Alexander von Humboldt", Universidad Peruana Cayetano Heredia, Lima 31, Peru
| | - Theresa J Ochoa
- b Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.,c University of Texas School of Public Health, Houston, TX 77030, USA
| |
Collapse
|
|
45
|
Waidyatillake NT, Simpson JA, Allen KJ, Lodge CJ, Dharmage SC, Abramson MJ, De Livera AM, Matheson MC, Erbas B, Hill DJ, Lowe AJ. The effect of breastfeeding on lung function at 12 and 18 years: a prospective cohort study. Eur Respir J 2016; 48:125-32. [PMID: 27076592 DOI: 10.1183/13993003.01598-2015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 02/29/2016] [Indexed: 12/25/2022]
Abstract
The objective was to assess associations between duration of total and exclusive breastfeeding and lung function up to adolescence.A birth cohort (Melbourne Atopy Cohort Study) of 620 infants with a family history of allergic disease was recruited. Mothers were encouraged to breastfeed exclusively for 6 months. Lung function was assessed at 12 and 18 years of age. Associations between breastfeeding and lung function were investigated using multivariable linear regression and path analysis was used to assess the potential mediating factors.Duration of breastfeeding (total and exclusive) was not associated with most assessed lung function outcomes. However, there was a trend for increased pre-bronchodilator mid-expiratory flow (MEF) at both 12 (adjusted mean difference (95% CI) per week of breastfeeding of 10 (-1-20) mL·s(-1)) and 18 years (11 (-1-22) mL·s(-1)) (p-values of 0.07 and 0.08, respectively). There was a strong indirect effect of height on these observed associations.Duration of breastfeeding does not appear to greatly influence lung function outcomes in children with a family history of allergic diseases. Longer duration of exclusive breastfeeding may be associated with an increase in MEF, partly due to greater attained height of the child.
Collapse
Affiliation(s)
- Nilakshi T Waidyatillake
- Allergy and Lung Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Carlton, Australia
| | - Julie A Simpson
- Biostatistics Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Carlton, Australia
| | | | - Caroline J Lodge
- Allergy and Lung Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Carlton, Australia Murdoch Childrens Research Institute, Melbourne, Australia
| | - Shyamali C Dharmage
- Allergy and Lung Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Carlton, Australia Murdoch Childrens Research Institute, Melbourne, Australia
| | - Michael J Abramson
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Alysha M De Livera
- Biostatistics Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Carlton, Australia
| | - Melanie C Matheson
- Allergy and Lung Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Carlton, Australia
| | - Bircan Erbas
- School of Psychology and Public Health, La Trobe University, Melbourne, Australia
| | - David J Hill
- Murdoch Childrens Research Institute, Melbourne, Australia
| | - Adrian J Lowe
- Allergy and Lung Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Carlton, Australia Murdoch Childrens Research Institute, Melbourne, Australia
| |
Collapse
|
|
46
|
Perrin MT, Fogleman AD, Newburg DS, Allen JC. A longitudinal study of human milk composition in the second year postpartum: implications for human milk banking. MATERNAL AND CHILD NUTRITION 2016; 13. [PMID: 26776058 DOI: 10.1111/mcn.12239] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 10/01/2015] [Accepted: 10/15/2015] [Indexed: 01/06/2023]
Abstract
While the composition of human milk has been studied extensively in the first year of lactation, there is a paucity of data regarding human milk composition beyond one year postpartum. Policies vary at milk banks around the world regarding how long lactating women are eligible to donate their milk. The primary purpose of this study is to describe longitudinal changes in human milk composition in the second year postpartum to support the development of evidence based guidelines regarding how long lactating women can donate human milk to a milk bank. Nineteen lactating women in North Carolina provided monthly milk samples from 11 months to 17 months postpartum (N = 131), and two non-profit milk banks provided (N = 33) pooled, unpasteurized milk samples from 51 approved donors less than one year postpartum. There was a significant increase (P < 0.05) in the concentration of total protein, lactoferrin, lysozyme, Immunoglobulin A, oligosaccharides and sodium in longitudinal samples of mother's milk between 11 and 17 months postpartum, while zinc and calcium concentrations declined, and no changes were observed in lactose, fat, iron and potassium. Human milk in the second year postpartum contained significantly higher concentrations of total protein, lactoferrin, lysozyme and Immunoglobulin A, than milk bank samples, and significantly lower concentrations of zinc, calcium, iron and oligosaccharides. Accepting milk bank donations beyond one year postpartum is a potential strategy for increasing the supply of donor milk, but may require mineral fortification.
Collapse
Affiliation(s)
- Maryanne T Perrin
- Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, North Carolina, USA
| | - April D Fogleman
- Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, North Carolina, USA
| | - David S Newburg
- Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA
| | - Jonathan C Allen
- Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, North Carolina, USA
| |
Collapse
|
|
47
|
Ke X, Chen Q, Pan X, Zhang J, Mo W, Ren Y. Quantification of lactoferrin in breast milk by ultra-high performance liquid chromatography-tandem mass spectrometry with isotopic dilution. RSC Adv 2016. [DOI: 10.1039/c5ra27243b] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
We developed a LC-MS/MS method for quantification of human lactoferrin in breast milk based on tryptic peptides and a synthetic isotopic peptide standard.
Collapse
Affiliation(s)
- Xing Ke
- College of Chemical Engineering
- Zhejiang University of Technology
- Hangzhou
- China
| | - Qi Chen
- Zhejiang Provincial Center for Disease Control and Prevention
- Hangzhou
- China
| | - Xiaodong Pan
- Zhejiang Provincial Center for Disease Control and Prevention
- Hangzhou
- China
| | - Jingshun Zhang
- Zhejiang Provincial Center for Disease Control and Prevention
- Hangzhou
- China
| | - Weimin Mo
- College of Chemical Engineering
- Zhejiang University of Technology
- Hangzhou
- China
| | - Yiping Ren
- Zhejiang Provincial Center for Disease Control and Prevention
- Hangzhou
- China
| |
Collapse
|
|
48
|
MicroRNAs in Breastmilk and the Lactating Breast: Potential Immunoprotectors and Developmental Regulators for the Infant and the Mother. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2015; 12:13981-4020. [PMID: 26529003 PMCID: PMC4661628 DOI: 10.3390/ijerph121113981] [Citation(s) in RCA: 148] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 10/21/2015] [Accepted: 10/27/2015] [Indexed: 12/12/2022]
Abstract
Human milk (HM) is the optimal source of nutrition, protection and developmental programming for infants. It is species-specific and consists of various bioactive components, including microRNAs, small non-coding RNAs regulating gene expression at the post-transcriptional level. microRNAs are both intra- and extra-cellular and are present in body fluids of humans and animals. Of these body fluids, HM appears to be one of the richest sources of microRNA, which are highly conserved in its different fractions, with milk cells containing more microRNAs than milk lipids, followed by skim milk. Potential effects of exogenous food-derived microRNAs on gene expression have been demonstrated, together with the stability of milk-derived microRNAs in the gastrointestinal tract. Taken together, these strongly support the notion that milk microRNAs enter the systemic circulation of the HM fed infant and exert tissue-specific immunoprotective and developmental functions. This has initiated intensive research on the origin, fate and functional significance of milk microRNAs. Importantly, recent studies have provided evidence of endogenous synthesis of HM microRNA within the human lactating mammary epithelium. These findings will now form the basis for investigations of the role of microRNA in the epigenetic control of normal and aberrant mammary development, and particularly lactation performance.
Collapse
|
|
49
|
McDade TW. Parent-offspring conflict and the cultural ecology of breast-feeding. HUMAN NATURE-AN INTERDISCIPLINARY BIOSOCIAL PERSPECTIVE 2015; 12:9-25. [PMID: 26191817 DOI: 10.1007/s12110-001-1011-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2000] [Accepted: 04/26/2000] [Indexed: 10/23/2022]
Abstract
Lactation constitutes a major focus for research in international health because of its dramatic impact on child survival; evolutionary biology has investigated lactation as an important aspect of parenting strategy, with implications for understanding parent-offspring conflict. These perspectives are brought together in an attempt to develop integrated models for an issue of key international health concern: the duration of exclusive breast-feeding and the timing of weaning. This analysis highlights the relevance of evolutionary theory for practical problems in public health, and it suggests the utility of public health outcomes for addressing evolutionary questions.
Collapse
Affiliation(s)
- T W McDade
- Department of Anthropology, Northwestern University, 1810 Hinman Avenue, 60208, Evanston, IL.
| |
Collapse
|
|
50
|
Hassiotou F, Geddes DT. Immune cell-mediated protection of the mammary gland and the infant during breastfeeding. Adv Nutr 2015; 6:267-75. [PMID: 25979492 PMCID: PMC4424778 DOI: 10.3945/an.114.007377] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Breastfeeding has been regarded first and foremost as a means of nutrition for infants, providing essential components for their unique growth and developmental requirements. However, breast milk is also rich in immunologic factors, highlighting its importance as a mediator of protection. In accordance with its evolutionary origin, the mammary gland offers via the breastfeeding route continuation of the maternal to infant immunologic support established in utero. At birth, the infant's immune system is immature, and although it was exposed to the maternal microbial flora during pregnancy, it experiences an abrupt change in its microbial environment during and after birth, which is challenging and renders the infant highly susceptible to infection. Active and passive immunity protects the infant via breast milk, which is rich in immunoglobulins, lactoferrin, lysozyme, cytokines, and numerous other immunologic factors, including maternal leukocytes. Breast milk leukocytes provide active immunity and promote development of immunocompetence in the infant. Additionally, it has been speculated that they play a role in the protection of the mammary gland from infection. Leukocytes are thought to exert these functions via phagocytosis, secretion of antimicrobial factors and/or antigen presentation in both the mammary gland and the gastrointestinal tract of the infant, and also in other infant tissues, where they are transported via the systemic circulation. Recently, it has been demonstrated that breast milk leukocytes respond dynamically to maternal as well as infant infections, and are fewer in nonexclusively compared with exclusively breastfeeding dyads, further emphasizing their importance for both the mother and infant. This review summarizes the current knowledge of human milk leukocytes and factors influencing them, and presents recent novel findings supporting their potential as a diagnostic marker for infections of the lactating breast and of the breastfed infant.
Collapse
Affiliation(s)
- Foteini Hassiotou
- School of Chemistry and Biochemistry, Faculty of Science, The University of Western Australia, Crawley, Australia
| | | |
Collapse
|